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Expression of a mitochondrial progesterone receptor (PR-M) in leiomyomata and association with increased mitochondrial membrane potential.

Publication ,  Journal Article
Feng, Q; Crochet, JR; Dai, Q; Leppert, PC; Price, TM
Published in: J Clin Endocrinol Metab
March 2014

CONTEXT: Clinical evidence supports a role for progestins in the growth of leiomyomata (fibroids). The mechanism(s) for this is thought to involve gene regulation via the nuclear progesterone receptors. Recently a mitochondrial progesterone receptor (PR-M) has been identified with evidence of a progesterone/progestin-dependent increase in cellular respiration. This observation raises a possible new mechanism whereby progesterone/progestin may affect the growth of fibroids. OBJECTIVE: The goals of this research were to determine differential expression of PR-M in normal myometrium compared with the edge of a fibroid within the same uterus, to demonstrate a progestin-dependent increase in mitochondria membrane potential using an immortalized human myometrial cell line and to examine mitochondrial membrane potential in transfected cells expressing the complete coding sequence of PR-M. DESIGN: Protein levels of PR-M, PR-B, PR-A, mitochondrial porin, and glyceraldehyde-3-phosphate dehydrogenase were determined in the myometrium and adjacent edge of a fibroid in 10 subjects undergoing hysterectomy for benign indications. Mitochondrial membrane potential was determined by fluorescent emission of 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolecarbocyanide iodine in hTERT-HM cells treated with R5020 and in transfected hTERT-HM cells determined by the fluorescent emission of tetramethylrhodamine methyl ester. RESULTS: Higher levels of PR-M and mitochondrial porin were found in the fibroid edge compared with adjacent myometrium. Progestin increased mitochondrial membrane potential in hTERT-HM cells, which was not affected by a translation inhibitor. This effect was exaggerated in hTERT-HM cells expressing PR-M after transient transfection. CONCLUSION: These studies suggest a mechanism whereby progesterone/progestin may affect the growth of fibroids by altering mitochondrial activity.

Duke Scholars

Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

March 2014

Volume

99

Issue

3

Start / End Page

E390 / E399

Location

United States

Related Subject Headings

  • Uterine Neoplasms
  • Tumor Cells, Cultured
  • Receptors, Progesterone
  • Progestins
  • Myometrium
  • Mitochondria, Muscle
  • Middle Aged
  • Membrane Potential, Mitochondrial
  • Leiomyoma
  • Humans
 

Citation

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MLA
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Feng, Q., Crochet, J. R., Dai, Q., Leppert, P. C., & Price, T. M. (2014). Expression of a mitochondrial progesterone receptor (PR-M) in leiomyomata and association with increased mitochondrial membrane potential. J Clin Endocrinol Metab, 99(3), E390–E399. https://doi.org/10.1210/jc.2013-2008
Feng, Quanling, John R. Crochet, Qunsheng Dai, Phyllis C. Leppert, and Thomas M. Price. “Expression of a mitochondrial progesterone receptor (PR-M) in leiomyomata and association with increased mitochondrial membrane potential.J Clin Endocrinol Metab 99, no. 3 (March 2014): E390–99. https://doi.org/10.1210/jc.2013-2008.
Feng Q, Crochet JR, Dai Q, Leppert PC, Price TM. Expression of a mitochondrial progesterone receptor (PR-M) in leiomyomata and association with increased mitochondrial membrane potential. J Clin Endocrinol Metab. 2014 Mar;99(3):E390–9.
Feng, Quanling, et al. “Expression of a mitochondrial progesterone receptor (PR-M) in leiomyomata and association with increased mitochondrial membrane potential.J Clin Endocrinol Metab, vol. 99, no. 3, Mar. 2014, pp. E390–99. Pubmed, doi:10.1210/jc.2013-2008.
Feng Q, Crochet JR, Dai Q, Leppert PC, Price TM. Expression of a mitochondrial progesterone receptor (PR-M) in leiomyomata and association with increased mitochondrial membrane potential. J Clin Endocrinol Metab. 2014 Mar;99(3):E390–E399.
Journal cover image

Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

March 2014

Volume

99

Issue

3

Start / End Page

E390 / E399

Location

United States

Related Subject Headings

  • Uterine Neoplasms
  • Tumor Cells, Cultured
  • Receptors, Progesterone
  • Progestins
  • Myometrium
  • Mitochondria, Muscle
  • Middle Aged
  • Membrane Potential, Mitochondrial
  • Leiomyoma
  • Humans