Department of Obstetrics and Gynecology (Q.F.), The First Affiliated Hospital, Zhengzhou University, Henan Zhengzhou, China 450052; and Department of Obstetrics and Gynecology (J.R.C., Q.D., P.C.L., T.M.P.), Division of Reproductive Endocrinology and Infertility, and Department of Pathology (P.C.L.), Duke University Medical Center, Duke University, Durham, North Carolina 27713.
J Clin Endocrinol Metab. 2014 Mar;99(3):E390-9. doi: 10.1210/jc.2013-2008. Epub 2014 Jan 13.
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.
临床证据表明孕激素在子宫肌瘤（纤维瘤）的生长中起作用。其作用机制被认为涉及核孕激素受体的基因调控。最近，已经鉴定出一种线粒体孕激素受体（PR-M），并且有证据表明孕激素/孕酮依赖性增加细胞呼吸。这一观察结果提出了一种新的可能机制，即孕激素/孕酮可能影响纤维瘤的生长。
本研究的目的是确定 PR-M 在正常子宫肌层与同一子宫内纤维瘤边缘的差异表达，用永生化人子宫平滑肌细胞系证明孕激素依赖性增加线粒体膜电位，并检测表达 PR-M 完整编码序列的转染细胞中线粒体膜电位。
在因良性原因接受子宫切除术的 10 名患者中，测定子宫肌层和肌瘤边缘的 PR-M、PR-B、PR-A、线粒体孔蛋白和甘油醛-3-磷酸脱氢酶的蛋白水平。用 R5020 处理 hTERT-HM 细胞和用荧光发射测定瞬时转染 hTERT-HM 细胞的四甲基罗丹明甲酯测定线粒体膜电位。
在肌瘤边缘发现 PR-M 和线粒体孔蛋白的水平高于相邻的子宫肌层。孕激素增加了 hTERT-HM 细胞的线粒体膜电位，而翻译抑制剂对其没有影响。在瞬时转染表达 PR-M 的 hTERT-HM 细胞中，这种作用被夸大。
这些研究表明，孕激素/孕酮可能通过改变线粒体活性来影响纤维瘤的生长的一种机制。
