Scholars@Duke
Michael Scott Freemark

Michael Scott Freemark

Robert C. Atkins, M.D. and Veronica Atkins Distinguished Professor of Pediatrics, in the School of Medicine
Pediatrics, Endocrinology
freem001@mc.duke.edu
Box 102820 Med Ctr, Durham, NC 27710
Suite 200, Lenox Baker Children's Hospital, 3000 Erwin Road, Durham, NC 27710

Selected Publications

Clinical and biochemical responses to treatment of uncomplicated severe acute malnutrition: a multicenter observational cohort from the OptiDiag study.

Journal Article Am J Clin Nutr · September 2024 BACKGROUND: Severe acute malnutrition (SAM) can be diagnosed using weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC). Although some favor using MUAC alone, valuing its presumed ability to identify children at greatest need for nutri ... Full text Link to item Cite

Sex Differences in Branched-chain Amino Acid and Tryptophan Metabolism and Pathogenesis of Youth-onset Type 2 Diabetes.

Journal Article J Clin Endocrinol Metab · March 15, 2024 OBJECTIVES: Insulin resistance is associated with elevations in plasma branched-chain amino acids (BCAAs). BCAAs compete with aromatic amino acids including tryptophan for uptake into β cells. To explore relationships between BCAAs and tryptophan metabolis ... Full text Link to item Cite

Catabolism of fats and branched-chain amino acids in children with Type 1 diabetes: Association with glycaemic control and total daily insulin dose.

Journal Article Endocrinol Diabetes Metab · November 2023 OBJECTIVE: Hyperglycaemia in Type 1 diabetes (T1D) results from an absolute insulin deficiency. However, insulin resistance (IR) may exacerbate glycaemic instability in T1D and contribute to long-term cardiovascular complications. We previously showed that ... Full text Link to item Cite

Hormonal Determinants of Growth and Weight Gain in the Human Fetus and Preterm Infant.

Journal Article Nutrients · September 18, 2023 The factors controlling linear growth and weight gain in the human fetus and newborn infant are poorly understood. We review here the changes in linear growth, weight gain, lean body mass, and fat mass during mid- and late gestation and the early postnatal ... Full text Link to item Cite

Evaluation of Autonomic Nervous System Dysfunction in Childhood Obesity and Prader-Willi Syndrome.

Journal Article Int J Mol Sci · April 28, 2023 The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader-Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations ... Full text Link to item Cite

Branched-chain α-keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity.

Journal Article Endocrinol Diabetes Metab · January 2023 OBJECTIVES: Insulin resistance (IR) in adolescents with obesity is associated with a sex-dependent metabolic 'signature' comprising the branched-chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the level ... Full text Link to item Cite

Disrupted Circadian Rhythm of Epinephrine in Males With Youth-Onset Type 2 Diabetes.

Journal Article J Endocr Soc · December 15, 2022 CONTEXT: Blood pressure and plasma catecholamines normally decline during sleep and rapidly increase in early morning. This is blunted in adults with type 2 diabetes (T2D). OBJECTIVE: We hypothesize that increased sympatho-adrenal activity during sleep dif ... Full text Link to item Cite

Impact of lifestyle Intervention on branched-chain amino acid catabolism and insulin sensitivity in adolescents with obesity.

Journal Article Endocrinol Diabetes Metab · July 2021 UNLABELLED: Insulin resistance in adolescents with obesity associates with a sex-dependent metabolic 'signature' comprising branched-chain amino acids (BCAAs), glutamate and C3/C5 acylcarnitines (C3/C5), implicating altered flux through BCAA catabolic path ... Full text Link to item Cite

Clinical and Biochemical Markers of Risk in Uncomplicated Severe Acute Malnutrition.

Journal Article Pediatrics · June 2021 BACKGROUND AND OBJECTIVES: Use of mid-upper arm circumference (MUAC) as a single screening tool for severe acute malnutrition (SAM) assumes that children with a low weight-for-height z score (WHZ) and normal MUAC have lower risks of morbidity and mortality ... Full text Link to item Cite

Hypothalamic-pituitary dysfunction in alternating hemiplegia of childhood.

Journal Article Eur J Paediatr Neurol · May 2021 BACKGROUND: Many central nervous system disorders result in hypothalamic-pituitary (HP) axis dysfunction. Alternating Hemiplegia of Childhood (AHC) is usually caused by mutations in the ATP1A3 subunit of the Na+/K+ ATPase, predominantly affecting GABAergic ... Full text Link to item Cite

Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial.

Journal Article Trials · February 17, 2021 BACKGROUND: Accumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal ... Full text Link to item Cite

Branched-Chain Amino Acid Catabolism and Cardiopulmonary Function Following Acute Maximal Exercise Testing in Adolescents.

Journal Article Front Cardiovasc Med · 2021 Background: To provide energy for cardiopulmonary function and maintenance of blood glucose, acute aerobic exercise induces lipolysis, fatty acid oxidation (FAO), glycolysis, and glycogenolysis/gluconeogenesis. These adaptations are mediated by increases i ... Full text Link to item Cite

Role of GLP-1 Receptor Agonists in Pediatric Obesity: Benefits, Risks, and Approaches to Patient Selection.

Journal Article Curr Obes Rep · December 2020 PURPOSE OF REVIEW: Effective treatments for pediatric obesity are limited. Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as therapeutic agents for obesity in adults and have shown benefits outside of weight loss. Here we explore the evide ... Full text Link to item Cite

Dietary macronutrient regulation of acyl and desacyl ghrelin concentrations in children with Prader-Willi syndrome (PWS).

Journal Article Clin Endocrinol (Oxf) · November 2020 BACKGROUND: The effects of dietary macronutrients on orexigenic and anorexigenic hormones in children are poorly understood. OBJECTIVE: To explore effects of varying dietary macronutrients on appetite-regulating hormones [acyl ghrelin (AG) and desacyl ghre ... Full text Link to item Cite

Obestatin and adropin in Prader-Willi syndrome and nonsyndromic obesity: Associations with weight, BMI-z, and HOMA-IR.

Journal Article Pediatr Obes · May 2019 The roles of obestatin and adropin in paediatric obesity are poorly understood. We compared obestatin and adropin concentrations in younger (n = 21) and older children (n = 14) with Prader-Willi syndrome (PWS) and age and BMI-z-matched controls (n = 31). F ... Full text Link to item Cite

Hormonal and metabolic effects of carbohydrate restriction in children with Prader-Willi syndrome.

Journal Article Clin Endocrinol (Oxf) · April 2019 OBJECTIVE: Macronutrient regulation of hyperphagia and adiposity in Prader-Willi syndrome (PWS) is poorly understood. We compared fasting and postprandial concentrations of hormones and metabolites in eight PWS children (age 9-18 years) fed, in random orde ... Full text Link to item Cite

Determinants of Risk for Childhood Obesity.

Journal Article N Engl J Med · October 4, 2018 Full text Link to item Cite

Sex- and age-dependent effects of celiac disease on growth and weight gain in children with type 1 diabetes: Analysis of the type 1 diabetes Exchange Clinic Registry.

Journal Article Pediatr Diabetes · June 2018 BACKGROUND: Celiac disease (CD) is common in patients with type 1 diabetes (T1D) and effects of CD on growth in children with T1D remain unclear. METHODS: We analyzed heights, weights, and body mass index (BMI) in 215 matched pediatric CD/control pairs in ... Full text Link to item Cite

Pediatric Obesity Etiology, Pathogenesis and Treatment

Book · January 5, 2018 Etiology, Pathogenesis and Treatment Michael S. Freemark ... This serves to reduce the risks of obesity among the more educated and professional classes. ... Other major factors that Table 1.2 Medications that promote weight gain Atypical ( second-genera ... Cite

Obesity and the endocrine system, Part II: The effects of childhood obesity on growth and bone maturation, thyroid and adrenal function, sexual development, and bone mineralization

Chapter · January 1, 2018 The storage of excess body fat has profound effects on intermediary metabolism and endocrine function. Here, I review the effects of obesity on linear growth and bone maturation, thyroid function, sexual development, adrenal function, calcium homeostasis, ... Full text Cite

Preface to the second edition

Book · January 1, 2018 Cite

Obesity and the endocrine system, part I: Pathogenesis of weight gain in endocrine and metabolic disorders

Chapter · January 1, 2018 Certain endocrine and metabolic disorders cause mild to moderate weight gain and fat deposition. Excess fat storage in turn can have profound effects on intermediary metabolism and endocrine function. In this chapter, I present a brief discussion of the pa ... Full text Cite

Brown adipose tissue and body weight regulation

Chapter · January 1, 2018 Brown adipose tissue plays a critical role in neonatal thermogenesis, insuring survival of the newborn infant during the transition from intrauterine to extrauterine life. In rodents, the generation and/or expansion of brown adipose tissue within white adi ... Full text Cite

Childhood obesity in the modern age: Global trends, determinants, complications, and costs

Chapter · January 1, 2018 This chapter highlights major global trends in the prevalence of childhood obesity and reviews the biological, social, economic, and cultural determinants of excess weight gain. It then summarizes the pathogenesis of acute and long-term complications of pe ... Full text Cite

Preface to the second edition

Book · January 1, 2018 Cite

Early-Onset Obesity Caused by Monogenic Disorders

Journal Article Current Pediatrics Reports · September 1, 2017 Purpose of Review: Obesity is a common problem encountered daily by pediatricians. Although most obesity results from an “obesogenic” environment, single gene mutations in the hypothalamic leptin-melanocortin pathway may cause severe hyperphagia and early- ... Full text Cite

Inkjet-printed point-of-care immunoassay on a nanoscale polymer brush enables subpicomolar detection of analytes in blood.

Journal Article Proc Natl Acad Sci U S A · August 22, 2017 The ELISA is the mainstay for sensitive and quantitative detection of protein analytes. Despite its utility, ELISA is time-consuming, resource-intensive, and infrastructure-dependent, limiting its availability in resource-limited regions. Here, we describe ... Full text Link to item Cite

Hormone signaling and fatty liver in females: analysis of estrogen receptor α mutant mice.

Journal Article Int J Obes (Lond) · June 2017 BACKGROUND: Treatment with estrogen in early menopausal women protects against development of hepatic steatosis and nonalcoholic fatty liver disease but estrogen has undesirable side effects, which negate its beneficial effects in premenopausal and postmen ... Full text Link to item Cite

A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay.

Journal Article Am J Hum Genet · February 2, 2017 Whole-exome sequencing (WES) has increasingly enabled new pathogenic gene variant identification for undiagnosed neurodevelopmental disorders and provided insights into both gene function and disease biology. Here, we describe seven children with a neurode ... Full text Link to item Cite

Environmental Enteric Dysfunction and Growth Failure/Stunting in Global Child Health.

Journal Article Pediatrics · December 2016 Approximately 25% of the world's children aged <5 years have stunted growth, which is associated with increased mortality, cognitive dysfunction, and loss of productivity. Reducing by 40% the number of stunted children is a global target for 2030. The path ... Full text Link to item Cite

De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype.

Journal Article Am J Hum Genet · October 6, 2016 The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 ... Full text Link to item Cite

Metabolic profiling in Prader-Willi syndrome and nonsyndromic obesity: sex differences and the role of growth hormone.

Journal Article Clin Endocrinol (Oxf) · December 2015 OBJECTIVES: To identify metabolic factors controlling appetite and insulin sensitivity in PWS and assess effects of GH treatment. METHODS: We compared amino acids, fatty acids and acylcarnitines in GH-treated and untreated PWS children and obese and lean c ... Full text Open Access Link to item Cite

Liraglutide in Weight Management.

Journal Article N Engl J Med · October 29, 2015 Full text Link to item Cite

Liraglutide in Weight Management

Journal Article The New England journal of medicine · October 29, 2015 Full text Cite

Macronutrient Regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader-Willi Syndrome.

Journal Article J Clin Endocrinol Metab · October 2015 BACKGROUND: The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and Prader-Willi Syndrome (PWS) are poorly understood. OBJECTIVE: We compared effects of high-carbohydrate (HC) and high-fat (HF) meals and GH therapy on g ... Full text Link to item Cite

Premature pubarche in children with Pompe disease.

Journal Article J Pediatr · April 2015 Pompe disease (PD), or glycogen storage disease type II, results from deficiency of acid α-glucosidase. Patients with infantile-onset PD die by early childhood if untreated. Patient survival has improved with enzyme replacement therapy. We report a case se ... Full text Link to item Cite

Metabolomics in nutrition research: biomarkers predicting mortality in children with severe acute malnutrition.

Journal Article Food Nutr Bull · March 2015 BACKGROUND: Millions of the world's children suffer from malnutrition, which predisposes to death from diarrhea and a variety of infectious diseases. Mortality rates among infants and toddlers remain staggeringly high, in part because the pathogenesis of a ... Full text Link to item Cite

Sex differences in biomarkers associated with insulin resistance in obese adolescents: metabolomic profiling and principal components analysis.

Journal Article J Clin Endocrinol Metab · December 2014 OBJECTIVE: Obesity and insulin resistance (IR) predispose to type 2 diabetes mellitus. Yet only half of obese adolescents have IR and far fewer progress to type 2 diabetes mellitus. We hypothesized that amino acid and fatty acid metabolites may serve as bi ... Full text Link to item Cite

Endocrinopathies of the Premature Infant

Chapter · October 6, 2014 Improve medical and developmental outcomes in high-risk infants with evidence-based management strategies Beyond the NICU is the first book to deliver practical, evidence-based strategies for healthcare providers caring for the NICU ... ... Cite

Screening for metabolic and reproductive complications in obese children and adolescents.

Journal Article Pediatr Ann · September 2014 Childhood obesity is associated with a number of metabolic comorbidities. These include glucose intolerance and type 2 diabetes mellitus, hyperlipidemia, fatty liver disease, and reproductive complications, such as polycystic ovary syndrome. The occurrence ... Full text Open Access Link to item Cite

Knockdown of prolactin receptors in a pancreatic beta cell line: effects on DNA synthesis, apoptosis, and gene expression.

Journal Article Endocrine · August 2014 Prolactin (PRL) and placental lactogen stimulate beta cell replication and insulin production in vitro and in vivo. The molecular mechanisms by which lactogens promote beta cell expansion are unclear. We treated rat insulinoma cells with a PRL receptor (PR ... Full text Link to item Cite

Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality.

Journal Article J Clin Endocrinol Metab · June 2014 OBJECTIVE: Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment. METHODS: We used targ ... Full text Link to item Cite

Effects of HIV infection on the metabolic and hormonal status of children with severe acute malnutrition.

Journal Article PLoS One · 2014 BACKGROUND: HIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood. METHODS: We conducted a prospective cohort study of 75 sev ... Full text Link to item Cite

Defective prolactin signaling impairs pancreatic β-cell development during the perinatal period.

Journal Article Am J Physiol Endocrinol Metab · November 15, 2013 Prolactin (PRL) and placental lactogens stimulate β-cell replication and insulin production in pancreatic islets and insulinoma cells through binding to the PRL receptor (PRLR). However, the contribution of PRLR signaling to β-cell ontogeny and function in ... Full text Link to item Cite

Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia.

Journal Article Mol Genet Metab · June 2013 Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth i ... Full text Open Access Link to item Cite

Pathogenesis and prevention of type 2 diabetes: parental determinants, breastfeeding, and early childhood nutrition.

Journal Article Curr Diab Rep · February 2012 Among the factors predisposing to type 2 diabetes in children, adolescents, and young adults, the health and behavior of both the mother and father are critical. Prevention and treatment of parental nutritional disorders (including obesity and malnutrition ... Full text Link to item Cite

Placental hormones and the control of maternal metabolism and fetal growth.

Journal Article Curr Opin Endocrinol Diabetes Obes · December 2011 PURPOSE OF REVIEW: To examine the roles of the placental and pituitary hormones in the control of maternal metabolism and fetal growth. RECENT FINDINGS: In addition to promoting growth of maternal tissues, placental growth hormone (GH-V) induces maternal i ... Full text Link to item Cite

Management of adolescents with polycystic ovary syndrome.

Journal Article J Clin Endocrinol Metab · November 2011 Full text Link to item Cite

Differential and complementary effects of glucose and prolactin on islet DNA synthesis and gene expression.

Journal Article Endocrinology · March 2011 The mechanisms by which lactogenic hormones promote β-cell expansion remain poorly understood. Because prolactin (PRL) up-regulates β-cell glucose transporter 2, glucokinase, and pyruvate dehydrogenase activities, we reasoned that glucose availability migh ... Full text Link to item Cite

Autonomic nervous system dysfunction in obesity and Prader-Willi syndrome: Current evidence and implications for future obesity therapies

Journal Article Clinical Obesity · January 1, 2011 The autonomic nervous system (ANS) controls essential functions like breathing, heart rate, digestion, body temperature and hormone levels. Evidence suggests that ANS dysfunction is associated with adult and childhood obesity and plays a role in the distri ... Full text Cite

The metabolic phenotype of Prader-Willi syndrome (PWS) in childhood: heightened insulin sensitivity relative to body mass index.

Journal Article J Clin Endocrinol Metab · January 2011 Featured Publication CONTEXT: Insulin sensitivity is higher in patients with Prader-Willi syndrome (PWS) than in body mass index-matched obese controls (OCs). Factors contributing to the heightened insulin sensitivity of PWS remain obscure. We compared the fasting levels of va ... Full text Link to item Cite

Regulation of islet beta-cell pyruvate metabolism: interactions of prolactin, glucose, and dexamethasone.

Journal Article Endocrinology · July 2010 Featured Publication Prolactin (PRL) induces beta-cell proliferation and glucose-stimulated insulin secretion (GSIS) and counteracts the effects of glucocorticoids on insulin production. The mechanisms by which PRL up-regulates GSIS are unknown. We used rat islets and insulino ... Full text Link to item Cite

Childhood Obesity

Journal Article · June 20, 2010 Full text Cite

Placental hormones and the control of fetal growth.

Journal Article J Clin Endocrinol Metab · May 2010 Featured Publication Full text Link to item Cite

The use of lipid-lowering drugs in children.

Journal Article J Clin Lipidol · 2010 Featured Publication Full text Link to item Cite

Prevention and treatment of pediatric obesity: an endocrine society clinical practice guideline based on expert opinion.

Journal Article J Clin Endocrinol Metab · December 2008 Featured Publication OBJECTIVE: Our objective was to formulate practice guidelines for the treatment and prevention of pediatric obesity. CONCLUSIONS: We recommend defining overweight as body mass index (BMI) in at least the 85th percentile but < the 95th percentile and obesit ... Full text Link to item Cite

Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children: changes during development.

Journal Article Clin Endocrinol (Oxf) · December 2008 Featured Publication BACKGROUND: Prader-Willi syndrome (PWS) is associated with failure to thrive in infancy and progressive hyperphagia and obesity in childhood. This progressive weight gain is associated with hyperghrelinaemia and increased insulin sensitivity. The role of g ... Full text Link to item Cite

The interplay of prolactin and the glucocorticoids in the regulation of beta-cell gene expression, fatty acid oxidation, and glucose-stimulated insulin secretion: implications for carbohydrate metabolism in pregnancy.

Journal Article Endocrinology · November 2008 Featured Publication Carbohydrate metabolism in pregnancy reflects the balance between counterregulatory hormones, which induce insulin resistance, and lactogenic hormones, which stimulate beta-cell proliferation and insulin production. Here we explored the interactions of pro ... Full text Link to item Cite

Acanthosis nigricans: a practical approach to evaluation and management.

Journal Article Dermatol Online J · September 15, 2008 Featured Publication Acanthosis nigricans is a dermatosis characterized by thickened, hyperpigmented plaques, typically of the intertriginous surfaces and neck. Common in some populations, its prevalence depends on race. Clinicians should recognize acanthosis nigricans; it her ... Link to item Cite

Seropositivity to celiac antigens in asymptomatic children with type 1 diabetes mellitus: association with weight, height, and bone mineralization.

Journal Article Pediatr Diabetes · July 28, 2008 Featured Publication BACKGROUND: Screening for celiac disease (CD) in children with diabetes is controversial because no studies have demonstrated metabolic complications in asymptomatic, seropositive subjects or beneficial effects of dietary intervention. OBJECTIVE: We hypoth ... Full text Link to item Cite

Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2.

Journal Article PLoS One · February 6, 2008 Featured Publication BACKGROUND: The lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding to PRL receptor (PRLR), highly expressed in brown adipose tissue (BAT), yet ... Full text Open Access Link to item Cite

Altered distribution of adiponectin isoforms in children with Prader-Willi syndrome (PWS): association with insulin sensitivity and circulating satiety peptide hormones.

Journal Article Clin Endocrinol (Oxf) · December 2007 Featured Publication OBJECTIVE: Prader-Willi syndrome (PWS) is a genetic syndrome characterized by relative hypoinsulinaemia and normal or increased insulin sensitivity despite profound obesity. We hypothesized that this increased insulin sensitivity is mediated by increased l ... Full text Link to item Cite

Effects of lactogen resistance and GH deficiency on mouse metabolism: pancreatic hormones, adipocytokines, and expression of adiponectin and insulin receptors.

Journal Article Endocrine · October 2007 Featured Publication We recently described a novel mouse model that combines resistance to lactogenic hormones with GH deficiency (GHD). The GHD/lactogen-resistant males develop obesity and insulin resistance with age. We hypothesized that altered production of pancreatic horm ... Full text Link to item Cite

Liver dysfunction in paediatric obesity: a randomized, controlled trial of metformin.

Journal Article Acta Paediatr · September 2007 Featured Publication AIM: In a previous study we showed that metformin reduced BMI z-scores and fasting glucose and insulin concentrations, and increased whole body insulin sensitivity in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. ... Full text Link to item Cite

Pharmacotherapy of childhood obesity: an evidence-based, conceptual approach.

Journal Article Diabetes Care · February 2007 Featured Publication Full text Link to item Cite

Lactogenic and somatogenic hormones regulate the expression of neuropeptide Y and cocaine- and amphetamine-regulated transcript in rat insulinoma (INS-1) cells: interactions with glucose and glucocorticoids.

Journal Article Endocrinology · January 2007 Featured Publication Lactogenic hormones stimulate food intake in rodents, ungulates, and birds. To test the hypothesis that lactogens regulate expression of neuropeptides that control appetite, we used the prolactin (PRL)-responsive rat insulinoma (INS-1) cell line as an expe ... Full text Link to item Cite

Regulation of maternal metabolism by pituitary and placental hormones: roles in fetal development and metabolic programming.

Journal Article Horm Res · 2006 Featured Publication This review outlines the regulation of maternal metabolism by hormones, cytokines and growth factors, highlighting recent studies that implicate disordered somatolactogen signalling in the pathogenesis of perinatal growth failure and the development of the ... Full text Link to item Cite

Growth hormone and prolactin receptors in adipogenesis: STAT-5 activation, suppressors of cytokine signaling, and regulation of insulin-like growth factor I.

Journal Article Horm Res · 2006 Featured Publication Growth hormone GH stimulates lipolysis in mature adipocytes and primary preadipocytes but promotes adipogenesis in preadipocyte cell lines. The lactogenic hormones (prolactin PRL and placental lactogen) also stimulate adipogenesis in preadipocyte cell line ... Full text Link to item Cite

Hormonal and metabolic consequences of childhood obesity.

Journal Article Endocrinol Metab Clin North Am · September 2005 Featured Publication It is apparent that chronic illnesses such as type 2 diabetes and cardiovascular disease originate in childhood. Obesity in childhood and adolescence hastens their development, enhances their rates of progression, increases the risks of severe complication ... Full text Link to item Cite

Childhood obesity.

Journal Article J Clin Endocrinol Metab · March 2005 Featured Publication In March 2004 a group of 65 physicians and other health professionals representing nine countries on four continents convened in Israel to discuss the widespread public health crisis in childhood obesity. Their aim was to explore the available evidence and ... Full text Link to item Cite

Type 2 diabetes in childhood: Diagnosis, pathogenesis, prevention, and treatment

Chapter · January 1, 2005 The 1985 edition of a major textbook of pediatrics described two forms of childhood diabetes mellitus: the autoimmune form of juvenile (now called type 1) diabetes, and a monogenic form of diabetes called maturity onset diabetes of the young (MODY). There ... Cite

Roles of the lactogens and somatogens in perinatal and postnatal metabolism and growth: studies of a novel mouse model combining lactogen resistance and growth hormone deficiency.

Journal Article Endocrinology · January 2005 Featured Publication To delineate the roles of the lactogens and GH in the control of perinatal and postnatal growth, fat deposition, insulin production, and insulin action, we generated a novel mouse model that combines resistance to all lactogenic hormones with a severe defi ... Full text Link to item Cite

Anti-obesity medication use in adolescents: risks and benefits.

Journal Article Pediatr Endocrinol Rev · November 2004 Featured Publication Pharmacological agents currently used to treat obese adolescents decrease appetite or reduce fat absorption from the gastrointestinal tract. This paper summarizes the indications for pharmacotherapy and the potential benefits and risks of anti-obesity medi ... Link to item Cite

Editorial: Growth hormone treatment of "idiopathic short stature": not so fast.

Journal Article J Clin Endocrinol Metab · July 2004 Featured Publication Full text Link to item Cite

The pathogenesis of insulin resistance in children: metabolic complications and the roles of diet, exercise and pharmacotherapy in the prevention of type 2 diabetes.

Journal Article Pediatr Endocrinol Rev · March 2004 Featured Publication In this manuscript we discuss the pathogenesis of type 2 diabetes in children, emphasizing the central importance of obesity, insulin resistance, dyslipidemia, hypertension and endothelial dysfunction. We then review critically the benefits of diet, exerci ... Link to item Cite

Pharmacologic approaches to the prevention of type 2 diabetes in high risk pediatric patients.

Journal Article J Clin Endocrinol Metab · January 2003 Featured Publication Full text Link to item Cite

Insulin pump therapy in toddlers and preschool children with type 1 diabetes mellitus.

Journal Article J Pediatr · October 2002 Featured Publication OBJECTIVE: To test whether glycemic control in young children could be achieved more effectively and safely by using continuous insulin infusions administered by insulin pumps. STUDY DESIGN: We analyzed the effects of pump therapy in nine toddlers in whom ... Full text Link to item Cite

Thyroxine supplementation in preterm infants: critical analysis.

Journal Article Curr Opin Pediatr · August 2002 Featured Publication Full text Link to item Cite

Leptin in the newborn mouse. Plasma concentrations, characterization of the circulating hormone, and tissue source.

Journal Article Biol Neonate · August 2002 Featured Publication Previous studies suggested that brown adipose tissue (BAT) provides a source of circulating leptin in the newborn mouse. However, we detected no leptin mRNA in newborn BAT or in newborn liver or stomach. In contrast, leptin expression was detected readily ... Full text Link to item Cite

Targeted deletion of the PRL receptor: effects on islet development, insulin production, and glucose tolerance.

Journal Article Endocrinology · April 2002 Featured Publication PRL and placental lactogen (PL) stimulate beta-cell proliferation and insulin gene transcription in isolated islets and rat insulinoma cells, but the roles of the lactogenic hormones in islet development and insulin production in vivo remain unclear. To cl ... Full text Link to item Cite

Prolactin induction of insulin gene transcription: roles of glucose and signal transducer and activator of transcription 5.

Journal Article Endocrinology · July 2001 Featured Publication GH and PRL stimulate insulin production in pancreatic beta-cells through induction of insulin gene transcription. The transcriptional effects of GH are mediated through the binding of signal transducer and activator of transcription-5 (STAT5) to a consensu ... Full text Link to item Cite

Prolactin receptor signal transduction pathways and actions determined in prolactin receptor knockout mice.

Journal Article Biochem Soc Trans · May 2001 Featured Publication Prolactin-receptor-deficient mice are a good model in which to study the various actions of prolactin. Female homozygous knockout mice are completely infertile and show a lack of mammary development, while hemizogotes are unable to lactate following their ... Full text Link to item Cite

Ontogenesis of prolactin receptors in the human fetus: roles in fetal development.

Journal Article Biochem Soc Trans · May 2001 Featured Publication The lactogenic hormones prolactin (PRL) and placental lactogen circulate in human fetal plasma during mid and late gestation. To explore potential roles for the lactogens in fetal development, we examined the cellular distribution and changes in expression ... Full text Link to item Cite

The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes.

Journal Article Pediatrics · April 2001 Featured Publication OBJECTIVES: The prevalence of type 2 diabetes in American adolescents has increased markedly during the past generation. Although the factors that contribute to the development of type 2 diabetes are complex and not wholly elucidated, the triad of severe o ... Full text Link to item Cite

Body weight and fat deposition in prolactin receptor-deficient mice.

Journal Article Endocrinology · February 2001 Featured Publication To explore the roles of the lactogens in adipose tissue development and function, we measured body weight, abdominal fat content, and plasma leptin concentrations in a unique model of lactogen resistance: the PRL receptor (PRLR)-deficient mouse. The absenc ... Full text Link to item Cite

The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development.

Journal Article J Pediatr Endocrinol Metab · April 2000 Featured Publication The human growth hormone (hGH)/human placental lactogen (hPL) gene family, which consists of two GH and three PL genes, is important in the regulation of maternal and fetal metabolism and the growth and development of the fetus. During pregnancy, pituitary ... Full text Link to item Cite

Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2.

Journal Article J Endocrinol · March 2000 Featured Publication Previous studies have shown that lactogenic hormones stimulate beta-cell proliferation and insulin production in pancreatic islets. However, all such studies have been conducted in cells incubated in medium containing glucose. Since glucose independently s ... Full text Link to item Cite

Constitutive expression of placental lactogen in pancreatic beta cells: effects on cell morphology, growth, and gene expression.

Journal Article Pediatr Res · January 2000 Featured Publication To explore the roles of lactogens in islet function, we generated a stable line of rat insulinoma (INS-1) cells that express rat placental lactogen II (rPLII) constitutively in culture. We used this cell line (Ins-rPLII) to examine the effects of endogenou ... Full text Link to item Cite

Ontogenesis of prolactin receptors in the human fetus in early gestation. Implications for tissue differentiation and development.

Journal Article J Clin Invest · March 1, 1997 Featured Publication To explore potential roles for lactogenic hormones in human fetal development, we examined the distribution and ontogenesis of expression of prolactin receptors (PRLRs) in human fetal tissues at 7.5-14 wk of gestation and in tissues of the embryonic and fe ... Full text Link to item Cite

Ontogenesis of prolactin receptor gene expression in the rat olfactory system: potential roles for lactogenic hormones in olfactory development.

Journal Article Endocrinology · March 1996 Featured Publication The PRL receptor (PRLR) is expressed at very low levels in the olfactory bulb of the adult rat but is detected in abundance in the olfactory epithelium and olfactory bulb of the fetal rat in late gestation. To explore potential roles for the lactogenic hor ... Full text Link to item Cite

The prolactin receptor in the fetal rat: cellular localization of messenger ribonucleic acid, immunoreactive protein, and ligand-binding activity and induction of expression in late gestation.

Journal Article Endocrinology · September 1995 Featured Publication The cellular distribution and developmental expression of the PRL receptor (PRLR) in the late gestational fetal rat were examined by in situ hybridization, immunohistochemistry, and radioligand binding. Antisense and sense strand RNA probes encoding the lo ... Full text Link to item Cite

Human placental lactogen infusions into the medial preoptic area stimulate maternal behavior in steroid-primed, nulliparous female rats.

Journal Article Horm Behav · June 1995 Featured Publication The effects of central administration of human placental lactogen (hPL) on the onset of maternal behavior were measured in steroid-primed, adult ovariectomized, nulliparous rats. Rats were fitted with bilateral cannulas directed at the medial preoptic area ... Full text Link to item Cite

Prolactin receptor gene expression in the fetal rat.

Journal Article J Endocrinol · February 1995 Featured Publication The expression of mRNA encoding the long and short forms of the prolactin receptor (PRLR) in the fetal rat was examined using the method of reverse transcription-PCR. A 742 bp PCR product encoding the extracellular and transmembrane domains of the PRLR was ... Full text Link to item Cite

Rat placental lactogen-I binds to the choroid plexus and hypothalamus of the pregnant rat.

Journal Article J Endocrinol · November 1993 Featured Publication Recent findings suggest that placental lactogen has a role in the regulation of hypothalamic function during pregnancy. To explore the mechanisms by which placental hormones may exert effects in the maternal central nervous system, we have examined the bin ... Full text Link to item Cite

Pregnancy lactogens in the rat conceptus and fetus: circulating levels, distribution of binding, and expression of receptor messenger ribonucleic acid.

Journal Article Endocrinology · October 1993 Featured Publication To clarify the roles of the rat placental lactogens in embryogenesis and fetal development, we measured the concentrations of rat placental lactogen-II (rPL-II) in fetal rat serum and examined the distribution and expression of rPL-I- and rPL-II-binding si ... Full text Link to item Cite

Placental lactogen-binding sites in isolated fetal fibroblasts: characterization, processing, and regulation.

Journal Article Endocrinology · June 1993 Featured Publication Placental lactogen (PL) stimulates amino acid transport, DNA synthesis, and insulin-like growth factor production in isolated fetal fibroblasts and myoblasts. To clarify the mechanisms by which PL exerts its effects in fetal tissues, we have examined the b ... Full text Link to item Cite

Evidence for a novel insulin-like growth factor (IGF)-dependent protease regulating IGF-binding protein-4 in dermal fibroblasts.

Journal Article Endocrinology · November 1992 Featured Publication The mechanisms by which insulin-like growth factors (IGFs) reduce IGF-binding protein-4 (IGFBP-4) levels in cellular conditioned media are poorly understood. The effect of IGFs on IGFBP-4 levels in fibroblast conditioned media is not mediated via the type ... Full text Link to item Cite

Nutritional regulation of insulin-like growth factor-binding protein gene expression in the ovine fetus and pregnant ewe.

Journal Article Endocrinology · October 1992 Featured Publication The factors controlling the synthesis and degradation of the insulin-like growth factor-binding proteins (IGFBPs) during pregnancy are poorly understood. To clarify the roles of nutritional factors in the regulation of fetal and maternal IGFBP production, ... Full text Link to item Cite

Binding of placental lactogen and growth hormone to fetal sheep fibroblasts.

Journal Article Pediatr Res · August 1992 Featured Publication Growth hormone (GH) regulates growth and development in the postnatal period but lacks somatotropic activity in the fetus. In contrast, the placental hormone placental lactogen (PL) stimulates amino acid transport, DNA synthesis, and somatomedin production ... Full text Link to item Cite

Developmental regulation of insulin-like growth factor binding protein production: studies in fetal, postnatal, and pregnant sheep.

Journal Article J Cell Physiol · July 1992 Featured Publication To assess the roles of developmental factors in the regulation of sheep IGFBP production at the cellular level, we characterized and compared the IGFBPs released by fetal, postnatal, and maternal sheep skin fibroblasts in culture with those in fetal, postn ... Full text Link to item Cite

The placental lactogen receptor in maternal and fetal sheep liver: regulation by glucose and role in the pathogenesis of fasting during pregnancy.

Journal Article Endocrinology · February 1992 Featured Publication To clarify the roles of glucose and insulin in the regulation of the PL receptor in fetal and maternal sheep liver, we administered iv glucose to pregnant ewes during a 72-h fast. The binding of ovine PL (oPL) to hepatic membranes from glucose-infused ewes ... Full text Link to item Cite

Placental lactogen receptors in maternal sheep liver: effects of fasting and refeeding.

Journal Article Am J Physiol · February 1990 Featured Publication In a recent study we demonstrated that fasting of the pregnant ewe reduces the number of placental lactogen (PL) receptors in fetal sheep liver. In the present study we examined the effects of a 72-h fast on the number and affinity of PL receptors in mater ... Full text Link to item Cite

Nutritional regulation of the placental lactogen receptor in fetal liver: implications for fetal metabolism and growth.

Journal Article Endocrinology · September 1989 Featured Publication We have recently identified and purified from fetal liver a distinct receptor that mediates the effects of placental lactogen (PL) on amino acid transport, glycogen synthesis, and somatomedin production in fetal tissues. At present, the factors that regula ... Full text Link to item Cite

The role of placental lactogen in the regulation of fetal metabolism and growth.

Journal Article J Pediatr Gastroenterol Nutr · April 1989 Featured Publication Full text Link to item Cite

Purification of a distinct placental lactogen receptor, a new member of the growth hormone/prolactin receptor family.

Journal Article J Clin Invest · March 1989 Featured Publication Recent findings from this laboratory suggest that the biological actions of placental lactogen (PL) in mammalian fetal tissues are mediated through binding of the hormone to a distinct and unique PL receptor. We have now purified this receptor from fetal a ... Full text Link to item Cite

Differential solubilization of placental lactogen (PL)- and growth hormone-binding sites: further evidence for a unique PL receptor in fetal and maternal liver.

Journal Article Endocrinology · June 1988 Featured Publication Previous studies from this laboratory provided evidence for the existence of a specific placental lactogen (PL) receptor in tissues of fetal lambs and pregnant sheep. The PL receptor is structurally and functionally distinct from somatotropic (GH) and lact ... Full text Link to item Cite

Placental lactogen and growth hormone receptors in human fetal tissues: relationship to fetal plasma human placental lactogen concentrations and fetal growth.

Journal Article J Clin Endocrinol Metab · June 1988 Featured Publication The specific binding of human placental lactogen (hPL) and human GH (hGH) to particulate cell membranes from human fetal liver and skeletal muscle at 12-19 weeks gestation was examined. Fetal liver and muscle specifically bound [125I]hPL. This binding was ... Full text Link to item Cite

Epidermal growth factor (EGF)-like transforming growth factor (TGF) activity and EGF receptors in ovine fetal tissues: possible role for TGF in ovine fetal development.

Journal Article Pediatr Res · November 1987 Featured Publication To determine whether epidermal growth factor (EGF) or EGF-like transforming growth factors (TGFs) are present in ovine fetal tissues, we have tested acid-ethanol extracts of ovine fetal kidney for the ability to induce anchorage-independent growth of norma ... Full text Link to item Cite

A unique placental lactogen receptor: implications for fetal growth.

Journal Article Endocrinology · May 1987 Featured Publication To determine whether there are structural differences between the binding sites for placental lactogen (PL) and GH, we have compared the molecular weights of complexes formed by the covalent cross-linking of [125I]ovine (o) PL and [125I]oGH to hepatic memb ... Full text Link to item Cite

Role of placental lactogen and prolactin in human pregnancy.

Journal Article Adv Exp Med Biol · 1987 Featured Publication In summary, studies from our and other laboratories strongly suggest that placental lactogen has direct effects on fetal growth and metabolism as well as on maternal metabolism. Prolactin may be important in the regulation of water and ion transport across ... Full text Link to item Cite

Placental lactogen and GH receptors in sheep liver: striking differences in ontogeny and function.

Journal Article Am J Physiol · September 1986 Featured Publication To determine whether changes in the relative biological potencies of ovine placental lactogen (oPL) and ovine growth hormone (oGH) during development derive from ontogenetic changes in the binding of these hormones to hepatic receptors, we have compared th ... Full text Link to item Cite

Epidermal growth factor stimulates glycogen synthesis in fetal rat hepatocytes: comparison with the glycogenic effects of insulin-like growth factor I and insulin.

Journal Article Endocrinology · August 1986 Featured Publication The effects of epidermal growth factor (EGF) on glycogen metabolism and the binding of [125I]iodo-EGF to receptors in fetal rat hepatocytes have been examined. The actions of EGF have been compared with those of insulin-like growth factor I (IGF-I) and ins ... Full text Link to item Cite

The glycogenic effects of placental lactogen and growth hormone in ovine fetal liver are mediated through binding to specific fetal ovine placental lactogen receptors.

Journal Article Endocrinology · February 1986 Featured Publication To examine the relative roles of placental lactogen (PL) and GH in fetal metabolism, we have examined the effects of ovine PL (oPL), ovine GH (oGH), and ovine PRL (oPRL) on glycogen metabolism in cultured ovine fetal hepatocytes and have examined the bindi ... Full text Link to item Cite

Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes.

Journal Article Endocrinology · June 1985 Featured Publication The effects of somatomedin-C/insulin-like growth factor I (Sm-C) on glycogen metabolism in cultured hepatocytes from 20-day-old rat fetuses have been examined and compared with the effects of insulin. Sm-C (25-375 ng/ml; 3.25-50 nM) stimulated dose-depende ... Full text Link to item Cite

Ovine placental lactogen inhibits glucagon-induced glycogenolysis in fetal rat hepatocytes.

Journal Article Endocrinology · April 1985 Featured Publication The effect of ovine placental lactogen (oPL) on glucagon-stimulated glycogenolysis was studied in cultured hepatocytes from 20-day-old fetal rats. Pretreatment of hepatocytes with oPL (0.5-5 micrograms/ml) significantly attenuated the inhibitory effect of ... Full text Link to item Cite

Synergistic effects of oPL and insulin on glycogen metabolism in fetal rat hepatocytes.

Journal Article Am J Physiol · December 1984 Featured Publication The interactions between ovine placental lactogen (oPL) and insulin in the regulation of fetal liver glycogen metabolism have been studied in cultured hepatocytes from fetal rats on day 20 of gestation. Both oPL (0.75-22.5 micrograms/ml) and insulin (0.01- ... Full text Link to item Cite

Synergistic effects of oPL and insulin on glycogen metabolism in fetal rat hepatocytes

Journal Article American Journal of Physiology - Endocrinology and Metabolism · December 1, 1984 The interactions between ovine placental lactogen (oPL) and insulin in the regulation of fetal liver glycogen metabolism have been studied in cultured hepatocytes from fetal rats on day 20 of gestation. Both oPL (0.75-22.5 μg/ml) and insulin (0.01-1 μM) st ... Cite

Glycogenolytic effects of the calcium ionophore A23187, but not of vasopressin or angiotensin, in foetal-rat hepatocytes.

Journal Article Biochem J · June 1, 1984 Featured Publication Vasopressin, angiotensin and phenylephrine stimulate glycogenolysis in postnatal rat liver by a Ca2+-mediated mechanism not involving cyclic AMP. To determine whether these hormones promote glycogenolysis in foetal liver, we have examined their effects, an ... Full text Link to item Cite

Ovine placental lactogen stimulates glycogen synthesis in fetal rat hepatocytes.

Journal Article Am J Physiol · January 1984 Featured Publication The effects of placental lactogen on glycogen metabolism have been studied in cultured hepatocytes from 20-day-old fetal rats. Ovine placental lactogen (oPL; 2, 5, 10, and 25 micrograms/ml) stimulated dose-dependent increases in [14C]glucose incorporation ... Full text Link to item Cite

Ovine placental lactogen stimulates glycogen synthesis in fetal rat hepatocytes

Journal Article American Journal of Physiology - Endocrinology and Metabolism · January 1, 1984 The effects of placental lactogen on glycogen metabolism have been studied in cultured hepatocytes from 20-day-old fetal rats. Ovine placental lactogen (oPL; 2, 5, 10, and 25 μg/ml) stimulated dose-dependent increases in [14C]glucose incorporation into gly ... Cite

Ovine placental lactogen, but not growth hormone, stimulates amino acid transport in fetal rat diaphragm.

Journal Article Endocrinology · January 1983 Featured Publication Previous studies from this laboratory indicate that ovine placental lactogen (oPL) and ovine growth hormone (oGH) stimulate amino acid transport in diaphragms of postnatal rats with equal potencies. However, in studies reported here using diaphragms from f ... Full text Link to item Cite

Ovine placental lactogen stimulates amino acid transport in rat diaphragm.

Journal Article Endocrinology · June 1982 Featured Publication Full text Link to item Cite

Case report. Atypical findings in adrenoleukodystrophy.

Journal Article J Comput Assist Tomogr · December 1981 Featured Publication Computed tomography (CT) in a child with typical clinical and biochemical features of adrenoleukodystrophy (ALD) revealed striking pathologic enhancement in the centra semiovalia, posterior corpus callosum, and corticospinal tracts within the internal caps ... Full text Link to item Cite

Streptobacillary rat-bite fever: a pediatric problem.

Journal Article Pediatrics · August 1979 Featured Publication A case of streptobacillary rat-bite fever in an 11-year-old boy from rural North Carolina is described. The child's clinical course was unique in that he developed a subglottic mass and bilateral parotid swelling. He responded initially to tetracycline but ... Link to item Cite

Testosterone-attenuated stereotype and hyperactivity induced by beta-phenylethylamine in pargyline-pretreated rats.

Journal Article Biol Psychiatry · August 1978 Featured Publication Testosterone pretreatment (1.0-4.0 mg/kg) attenuated, in a dose-response fashion, the induction of stereotyped behavior and hyperactivity by pargyline (0.25, 4.0 mg/kg) and beta-phenylethylamine (8.0, 16.0 mg/kg) in preubertal, male rats. The dyskinetic mo ... Link to item Cite