Bruce Lobaugh

The overall objective of my research is to characterize the mechanisms by which mineral homeostasis is achieved and skeletal integrity maintained in vertebrate species. This knowledge can then be applied to specific diseases to pinpoint pathogenic mechanisms and develop therapeutic strategies. Current areas of emphasis include:

· Regulation of vitamin D metabolism during pregnancy and lactation.
Using new assays for renal vitamin D hvdroxylase activities, "free" 1,25-
dihydroxyvitamin D and metabolic turnover of 1,25-dihydroxyvitamin D, we are investigating the regulation of this vitamin D hormone during pregnancy
and lactation. Results from these studies will supplement our existing data
on the mechanisms governing day-to-day regulation of vitamin D
metabolism and may yield insight into these processes during periods of special demand.

· Development of an animal model of human primary hyperparathyroidism.
Studies are ongoing to produce and fully characterize a murine model of human primary hyperparathyroidism (HPT). When rice-grain sized slivers of human parathyroid adenoma explants are inserted into gluteal pockets of athymic nude mice, persistent hypercalcemia and hypophosphatemia (>6 months duration) develop within several days in a percentage of the animals. Moreover, biosynthesis of 1, 25-dihydroxyvitamin D, a key hormone whose activation is modulated by parathyroid hormone (PTH), is also chronically stimulated. This model will allow: 1) study of the relationships between HPT and other conditions commonly associated with the disorder (e.g. hypertension, peptic ulcer disease, renal stones); 2) the regulation of vitamin D metabolism in HPT; 3) the natural history of bone disease in HPT; and 4) new nonsurgical techniques to localize and treat HPT.

Special areas of expertise include skeletal and mineral homeostasis, biometry, continuous quality improvement and clinical laboratory administration.

Key Words: calcium, phosphorus, Vitamin D, hyperparathyroidism, lactation, endocrinology