Tetsuka M, Thomas F J, Thomas M J, Anderson R A, Mason J I, Hillier S G
Department of Obstetrics and Gynaecology, University of Edinburgh School of Medicine, United Kingdom.
J Clin Endocrinol Metab. 1997 Jun;82(6):2006-9.
In glucocorticoid target organs 11beta-hydroxysteroid dehydrogenase (11betaHSD) regulates the levels of active glucocorticoids available to glucocorticoid receptors. To date two isoforms of 11betaHSD, NADP-dependent type 1 11betaHSD (11betaHSD1) with predominant reductase activity and NAD-dependent type 2 11betaHSD (11betaHSD2) with dehydrogenase activity have been identified. Human ovarian granulosa cells have been shown to possess both dehydrogenase and reductase 11betaHSD activities and express 11betaHSD1 mRNA. However, whether 11betaHSD2 mRNA is also present or if the expression of either mRNA is developmentally regulated in the human ovary is unknown. We therefore used northern analysis to examine 11betaHSD1 and 11betaHSD2 mRNA levels in non-luteinized and luteinizing granulosa cells, corpora lutea (CL) and ovarian stroma obtained from human ovaries. Here we show that non-luteinized granulosa cells express relatively high levels of 11betaHSD2 mRNA but not 11betaHSD1. Conversely, luteinizing granulosa cells abundantly express 11betaHSD1 mRNA but not 11betaHSD2. CL also expresses 11betaHSD2 to lesser extent. Neither 11betaHSD mRNA is detectable in ovarian stroma. These results indicate that mRNAs encoding both 1lbetaHSD isozymes are present in human granulosa cells and they are developmentally--but differentially--regulated during preovulatory follicular development. The existence of developmentally regulated 11betaHSD in human granulosa cells is important new evidence that glucocorticoids, acting directly on the ovary, serve physiologically significant roles in the regulation of folliculogenesis.
在糖皮质激素靶器官中，11β-羟类固醇脱氢酶（11βHSD）调节糖皮质激素受体可利用的活性糖皮质激素水平。迄今为止，已鉴定出11βHSD的两种同工型，即具有主要还原酶活性的NADP依赖性1型11βHSD（11βHSD1）和具有脱氢酶活性的NAD依赖性2型11βHSD（11βHSD2）。已证明人卵巢颗粒细胞同时具有脱氢酶和还原酶11βHSD活性，并表达11βHSD1 mRNA。然而，人卵巢中是否也存在11βHSD2 mRNA，或者这两种mRNA的表达是否受发育调控尚不清楚。因此，我们采用Northern印迹分析来检测从人卵巢获取的未黄体化和黄体化颗粒细胞、黄体（CL）及卵巢基质中11βHSD1和11βHSD2 mRNA的水平。在此我们发现，未黄体化颗粒细胞表达相对高水平的11βHSD2 mRNA，但不表达11βHSD1。相反，黄体化颗粒细胞大量表达11βHSD1 mRNA，但不表达11βHSD2。CL也较少程度地表达11βHSD2。在卵巢基质中未检测到任何一种11βHSD mRNA。这些结果表明，编码两种11βHSD同工酶的mRNA存在于人颗粒细胞中，并且它们在排卵前卵泡发育过程中受到发育调控，但调控方式存在差异。人颗粒细胞中存在受发育调控的11βHSD是重要的新证据，表明糖皮质激素直接作用于卵巢，在卵泡发生的调节中发挥着重要的生理作用。
