Gonadotropin-releasing hormone-dependent regulation of gonadotropin subunit messenger ribonucleic acid levels in the rat.
The Nal-Glu GnRH antagonist (GnRHA) was given to castrate male and female rats 7 days after gonadectomy to assess the impact of selective GnRH inhibition on the steady state mRNA levels of FSH beta, LH beta, and alpha-subunit and serum levels of FSH and LH. A low dose of GnRHA (125 micrograms/kg.day) given to female rats for 1, 3, or 7 days resulted in suppression of serum FSH and LH levels by 7 days to 50% and 40%, respectively, of ovariectomized control values. LH beta mRNA levels decreased in a time-dependent manner, so that by 7 days, LH beta mRNA levels were less than those in intact controls. There were significant but less dramatic declines in alpha and FSH beta mRNA levels. A higher dose of GnRHA (500 micrograms/kg.day) for 7 or 14 days administered to castrate male or female rats resulted in inhibition of serum LH and FSH to or below levels in intact controls. At this dose, all three gonadotropin subunit mRNA levels fell from castrate values toward or below those in intact controls. Thus, although low dose GnRHA administration suppressed LH beta mRNA more than FSH beta mRNA levels, high dose GnRHA treatment resulted in equal suppression of all three gonadotropin subunits. No stimulatory effects on alpha-subunit mRNA levels were observed with either dose of GnRHA. We conclude that the pretranslational control of gonadotropin subunit biosynthesis is GnRH dependent. Adequate dose and length of administration of the potent Nal-Glu GnRHA results in suppression of both the serum gonadotropins FSH and LH and the mRNAs for FSH beta, LH beta, and alpha-subunit in female and male rats.
Wierman
M E
ME
Department of Medicine, Veterans Administration Medical Center, Denver, Colorado 80220.
Rivier
J E
JE
Wang
C
C
D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000235:genetics*; D037201:Follicle Stimulating Hormone, beta Subunit; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood / Q000235:genetics*; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D037201:Follicle Stimulating Hormone, beta Subunit; C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone