Hillier S G, Smyth C D, Whitelaw P F, Miró F, Howles C M
Reproductive Endocrinology Laboratory, University of Edinburgh Centre for Reproductive Biology, UK.
Horm Res. 1995;43(5):216-23. doi: 10.1159/000184282.
It has been known for over 50 years that both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are required to stimulate both follicular development and oestradiol synthesis. However, previous experiments employing FSH and LH preparations (whether of pituitary or urinary origin) have not been able to answer unequivocally, whether an observed response was solely due to either FSH or LH because they were not pure preparations. In view of the recent availability of both 100% pure recombinant human FSH and recombinant human LH, we now have a unique opportunity to test their contribution in the regulation of ovarian function. Such experiments may have important clinical implications as they offer a means to interpret the effect of 'pure' FSH preparations when used to stimulate ovarian function in women undergoing different therapeutic regimens. To test the contribution of LH to optimize ovarian responsiveness to FSH, 21-day-old hypophysectomized, immature, female rats were treated for a 2-day period with varying total doses of rec-FSH (30-72 IU and/or rec-LH at 12-hourly intervals. At 48 h after the first injection, ovaries were removed, weighed and used to isolate granulosa and thecal interstitial cells for assessment of basal and gonadotrophin-responsive steroidogenesis in vitro; homogenized to extract total RNA for Northern analysis of 17-hydroxylase/C17-20-lyase (cytochrome P-450C17); mRMA; or examined using in situ hybridization to determine the expression of P-450C17 in the rat graafian follicle. The experiments demonstrated the potential for rec-FSH to influence LH-responsive androgen synthesis (via a paracrine mechanism) which involves an up-regulation of thecal P-450C17 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
五十多年来,人们一直知道促卵泡激素(FSH)和促黄体生成素(LH)都是刺激卵泡发育和雌二醇合成所必需的。然而,以往使用FSH和LH制剂(无论来源于垂体还是尿液)的实验都无法明确回答所观察到的反应是否仅归因于FSH或LH,因为它们不是纯制剂。鉴于最近已获得100%纯的重组人FSH和重组人LH,我们现在有了一个独特的机会来测试它们在调节卵巢功能中的作用。此类实验可能具有重要的临床意义,因为它们提供了一种手段,可用于解释在接受不同治疗方案的女性中使用“纯”FSH制剂刺激卵巢功能时的效果。为了测试LH对优化卵巢对FSH反应性的作用,对21日龄切除垂体的未成熟雌性大鼠进行为期2天的治疗,以不同总剂量的重组FSH(30 - 72 IU)和/或重组LH每隔12小时给药一次。首次注射后48小时,取出卵巢,称重,并用于分离颗粒细胞和卵泡膜间质细胞,以评估体外基础和促性腺激素反应性类固醇生成;匀浆以提取总RNA用于17 - 羟化酶/C17 - 20裂解酶(细胞色素P - 450C17)的Northern分析;mRNA;或使用原位杂交检查以确定大鼠格拉夫卵泡中P - 450C17的表达。实验证明了重组FSH通过旁分泌机制影响LH反应性雄激素合成的潜力,这涉及卵泡膜P - 450C17 mRNA的上调。(摘要截短于250字)