Expression of a Mitochondrial Progesterone Receptor (PR-M) in Leiomyomata and Association With Increased Mitochondrial Membrane Potential
| Autor: | Qunsheng Dai, Thomas M Price, Quanling Feng, Phyllis C. Leppert, John R. Crochet |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry Context (language use) Mitochondrion Biology Hot Topics in Translational Endocrinology Biochemistry Endocrinology Internal medicine Progesterone receptor Tumor Cells Cultured medicine Humans Receptor Membrane Potential Mitochondrial Regulation of gene expression Membrane potential Leiomyoma Biochemistry (medical) Myometrium Middle Aged female genital diseases and pregnancy complications Mitochondria Muscle Cell culture Uterine Neoplasms Female Progestins Receptors Progesterone |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 99:E390-E399 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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