Wiebe J P, Wood P H
Endocrinology. 1987 Jun;120(6):2259-64. doi: 10.1210/endo-120-6-2259.
Previous reports have not identified a naturally occurring steroid that selectively inhibits FSH secretion without also inhibiting LH secretion. The effect of 3 alpha-hydroxy-4-pregnen-20-one (3-HP), a steroid produced in Sertoli cells, on gonadotropin secretion in intact and castrate male and female, prepubertal and adult rats and in cultures of anterior pituitary cells was investigated. Intact prepubertal male rats were treated with a single sc injection of 0.2 mg/kg 3-HP, and castrate male and female rats were given a daily sc injection of 0.2 mg/kg 3-HP for 4 days. Serum FSH levels were suppressed by 26-44% (P less than 0.001-0.05), with no similar effect on serum LH levels. The acetyl derivative of 3-HP (3-HPA), administered to castrate prepubertal and adult rats for 4 days (0.625 mg/kg), resulted in significant decreases (P less than 0.001) in serum FSH to 45% and 19% of castrate control levels, respectively, without a significant effect on LH levels. Treatment of castrate prepubertal male rats with various doses of 3-HPA (0.001-0.625 mg/kg X day) for 4 days resulted in a dose-related suppression of serum FSH. Similar results were obtained with chronic (14-day) treatment of intact male rats with 3-HPA. Treatment of young (15-day-old) intact males with either 3-HP or 17 beta-hydroxy-5 alpha-androstan-3-one (DHT) for 14 days showed that DHT resulted in significant increases in prostate and seminal vesicle weights, while 3-HP showed no apparent androgenic activity. The effects of treatment with 3-HP, 3 beta-HP, 17 beta-estradiol, and DHT (0.025-0.625 mg/kg X day) were compared. Treatment with 3 beta-HP resulted in significant increases in serum FSH levels; 17 beta-estradiol and DHT suppressed both gonadotropins (at the higher doses administered), while 3-HP suppressed only FSH. 3-HP (3.16 X 10(-11) M) and/or LHRH (3 X 10(-8) M) were employed in primary cultures of anterior pituitary cells. Addition of LHRH resulted in 6- to 8-fold increases in the secretion of FSH and LH, while 3-HP suppressed basal (P less than 0.05) and LHRH-stimulated (P less than 0.001) FSH secretion by 26% and 77%, respectively. We conclude that 3-HP selectively suppresses FSH secretion and may be involved in the normal regulation of FSH secretion in the male.
以往的报告尚未发现一种天然存在的类固醇能选择性抑制促卵泡激素（FSH）分泌而不抑制促黄体生成素（LH）分泌。研究了睾丸支持细胞产生的一种类固醇3α-羟基-4-孕烯-20-酮（3-HP）对完整和去势的雄性及雌性、青春期前和成年大鼠以及垂体前叶细胞培养物中促性腺激素分泌的影响。对青春期前完整雄性大鼠单次皮下注射0.2mg/kg 3-HP，对去势的雄性和雌性大鼠每日皮下注射0.2mg/kg 3-HP，持续4天。血清FSH水平被抑制了26%-44%（P<0.001-0.05），而对血清LH水平无类似影响。给青春期前和成年去势大鼠连续4天给予3-HP的乙酰衍生物（3-HPA，0.625mg/kg），导致血清FSH显著降低（P<0.001），分别降至去势对照水平的45%和19%，而对LH水平无显著影响。对青春期前去势雄性大鼠用不同剂量的3-HPA（0.001-0.625mg/kg×天）连续治疗4天，导致血清FSH呈剂量相关的抑制。用3-HPA对完整雄性大鼠进行慢性（14天）治疗也得到了类似结果。对15日龄的完整雄性大鼠用3-HP或17β-羟基-5α-雄甾烷-3-酮（双氢睾酮，DHT）治疗14天，结果显示DHT导致前列腺和精囊重量显著增加，而3-HP未表现出明显的雄激素活性。比较了用3-HP、3β-HP、17β-雌二醇和DHT（0.025-0.625mg/kg×天）治疗的效果。用3β-HP治疗导致血清FSH水平显著升高；17β-雌二醇和DHT（在给予的较高剂量下）抑制了两种促性腺激素，而3-HP仅抑制FSH。在垂体前叶细胞原代培养中使用3-HP（3.16×10⁻¹¹M）和/或促性腺激素释放激素（LHRH，3×10⁻⁸M）。添加LHRH导致FSH和LH分泌增加6至8倍，而3-HP分别抑制基础（P<0.05）和LHRH刺激（P<0.001）的FSH分泌26%和77%。我们得出结论，3-HP选择性抑制FSH分泌，可能参与雄性FSH分泌的正常调节。
