Selective suppression of follicle-stimulating hormone by 3 alpha-hydroxy-4-pregnen-20-one, a steroid found in Sertoli cells.
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.
D004092:20-alpha-Dihydroprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000367:Age Factors; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011374:Progesterone / Q000031:analogs & derivatives*; D012636:Secretory Rate / Q000187:drug effects; D012708:Sertoli Cells / Q000502:physiology*; D013329:Structure-Activity Relationship
D004092:20-alpha-Dihydroprogesterone; C052610:3-hydroxypregn-4-en-20-one; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone