Androgen selectively stimulates follicle-stimulating hormone-beta mRNA levels after gonadotropin-releasing hormone antagonist administration.
Gonadal steroids act both at the hypothalamus and pituitary to regulate gonadotropin subunit gene expression. To investigate positive feedback effects of sex steroids on gonadotropin subunit mRNA levels in vivo, independent of effects on gonadotropin-releasing hormone (GnRH), the following studies were performed. Male and female rats, 7 days following castration, received the potent Nal/Glu GnRH antagonist (GnRHA) (500 micrograms/kg/day) for 14 days to block endogenous GnRH activity. Subgroups of animals received either estradiol benzoate (E) (10 micrograms/100 g BW/day) or testosterone propionate (T) (500 micrograms/100 g BW/day) for the last 7 days to assess the effects of reintroduction of gonadal steroids during blockade of endogenous GnRH action. Intact rats and castrated animals that received vehicle served as controls. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were determined on trunk blood, and gonadotropin subunit mRNAs were determined by blot hybridization using radiolabeled probes specific for the rat FSH beta, alpha, and LH beta subunit and mouse beta-actin genes. Autoradiographic bands were quantitated by laser densitometry and subunit mRNA levels were compared to those in intact pituitaries. In these studies, GnRHA administration inhibited the post-castration rises in all three gonadotropin mRNAs, as well as in serum FSH and LH levels. GnRHA + E or GnRHA + T resulted in similar or further suppression of alpha and LH beta mRNA levels compared to GnRHA alone. In contrast, in both sexes, GnRHA + T stimulated FSH beta mRNAs and serum FSH levels toward those of gonadectomized controls. Thus, during GnRHA inhibition of endogenous GnRH activity, androgen uniquely stimulates FSH beta mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Wierman
M E
ME
Department of Medicine, University of Colorado Health Sciences Center, Denver.
Wang
C
C
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology; D005246:Feedback; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000235:genetics*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000097:blood / Q000235:genetics; D008297:Male; D010906:Pituitary Hormone-Releasing Hormones / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000728:Androgens; D004967:Estrogens; C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D010906:Pituitary Hormone-Releasing Hormones; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone