Roberts V J, Barth S, el-Roeiy A, Yen S S
Department of Reproductive Medicine, University of California-San Diego, La Jolla 92037-0802.
J Clin Endocrinol Metab. 1994 Nov;79(5):1434-9. doi: 10.1210/jcem.79.5.7962340.
The role of inhibin, activin, and follistatin in the pathophysiology of polycystic ovary syndrome (PCOS) was investigated by examining the expression of human inhibin/activin subunit, follistatin, and type II activin receptor (ActRII and -IIB) messenger ribonucleic acid (mRNA) signals (via in situ hybridization) and encoded proteins (via immunocytochemistry) in ovarian follicles (n = 42) from 6 women diagnosed with PCOS. The localization patterns in cellular compartments were compared to those in small antral follicles of comparable size (3-7 mm; n = 40) from 17 normal human ovaries. In small antral follicles of both normal and PCOS ovaries, mRNA signals for all three subunits of inhibin and activin (alpha, beta a, and beta b) were expressed in granulosa cells, whereas in the thecal cell layer, only alpha-subunit mRNA was expressed. The relative intensity of the alpha-subunit mRNA signal was distinctly different in granulosa and thecal cells between PCOS and normal follicles; in small antral follicles of normal ovaries, the alpha-subunit mRNA signal was stronger in the granulosa cell layer than in the thecal cells, and the reverse was found in the polycystic follicles. A light follistatin mRNA signal was found in the granulosa cells of normal small antral follicles, but no follistatin mRNA was detected in any cell type of PCOS follicles. ActRII and -IIB mRNAs were not detected in any cell layer in either normal or PCOS follicles. There were no notable differences in the protein localization pattern of the inhibin/activin system between the PCOS and normal ovaries. In both types of follicles, follistatin and alpha-, beta a-, and beta b-subunit cytoplasmic staining were observed in granulosa cells, as were their corresponding messages, with the exception of the undetectable follistatin mRNA signal in the PCOS follicles. In both normal and PCOS follicles, follistatin and beta a-subunit cytoplasmic staining were occasionally found in thecal interna cells, with no corresponding localization of mRNA, and alpha-subunit protein was not detected in thecal cells despite the presence of the alpha-subunit mRNA. ActRII and -IIB protein localizations were not examined due to the lack of available antisera. These results suggest that granulosa cells of small antral follicles are less active in polycystic than in normal ovaries with respect to inhibin alpha-subunit and follistatin mRNA expression. A consequence of these differences could be an increase in the availability of activin, relative to inhibin, in the arrested follicles in PCOS.
通过原位杂交检测6例诊断为多囊卵巢综合征（PCOS）女性的42个卵巢卵泡中人类抑制素/激活素亚基、卵泡抑素及II型激活素受体（ActRII和-IIB）信使核糖核酸（mRNA）信号，并通过免疫细胞化学检测其编码蛋白，以研究抑制素、激活素和卵泡抑素在PCOS病理生理学中的作用。将细胞区室中的定位模式与17个正常人类卵巢中大小相当（3 - 7mm）的小窦卵泡（n = 40）中的定位模式进行比较。在正常和PCOS卵巢的小窦卵泡中，抑制素和激活素的所有三个亚基（α、βa和βb）的mRNA信号均在颗粒细胞中表达，而在卵泡膜细胞层中，仅表达α亚基mRNA。PCOS卵泡与正常卵泡的颗粒细胞和卵泡膜细胞中α亚基mRNA信号的相对强度明显不同；在正常卵巢的小窦卵泡中，颗粒细胞层中的α亚基mRNA信号强于卵泡膜细胞，而在多囊卵泡中则相反。在正常小窦卵泡的颗粒细胞中发现微弱的卵泡抑素mRNA信号，但在PCOS卵泡的任何细胞类型中均未检测到卵泡抑素mRNA。在正常或PCOS卵泡的任何细胞层中均未检测到ActRII和-IIB mRNA。PCOS卵巢与正常卵巢之间抑制素/激活素系统的蛋白质定位模式没有显著差异。在两种类型的卵泡中，颗粒细胞中均观察到卵泡抑素和α、βa和βb亚基的细胞质染色，以及它们相应的信使，PCOS卵泡中未检测到卵泡抑素mRNA信号除外。在正常和PCOS卵泡中，卵泡膜内层细胞偶尔会出现卵泡抑素和βa亚基的细胞质染色，没有相应的mRNA定位，尽管存在α亚基mRNA，但在卵泡膜细胞中未检测到α亚基蛋白。由于缺乏可用的抗血清，未检测ActRII和-IIB蛋白的定位。这些结果表明，就抑制素α亚基和卵泡抑素mRNA表达而言，PCOS中小窦卵泡的颗粒细胞活性低于正常卵巢。这些差异的一个后果可能是PCOS中停滞卵泡中激活素相对于抑制素的可用性增加。
