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

Published

Journal Article

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.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.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.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.These studies suggest a mechanism whereby progesterone/progestin may affect the growth of fibroids by altering mitochondrial activity.

Full Text

Duke Authors

Cited Authors

  • Feng, Q; Crochet, JR; Dai, Q; Leppert, PC; Price, TM

Published Date

  • March 2014

Published In

Volume / Issue

  • 99 / 3

Start / End Page

  • E390 - E399

PubMed ID

  • 24423317

Pubmed Central ID

  • 24423317

Electronic International Standard Serial Number (EISSN)

  • 1945-7197

International Standard Serial Number (ISSN)

  • 0021-972X

Digital Object Identifier (DOI)

  • 10.1210/jc.2013-2008

Language

  • eng