Pituitary receptor sites for gonadotropin-releasing hormone: effect of castration and substitutive therapy with sex steroids in the male rat.
To examine the role of pituitary gonadotropin-releasing hormone (GnRH) receptors (pit GnRH-R) in the regulation of gonadotropin secretion, male rats were orchidectomized and then selectively received substitutive therapy with sex steroids. Pituitary content of GnRH-R was determined by saturation analysis, using radioiodinated [D-Trp6,(N-Et)Pro5,des-Gly10]GnRH as tracer. Castration produced a rapid and sustained increase of the number of GnRH-R, which doubled after 2 days, and after 10 days the pituitary content of GnRH-R was 258 +/- 23 fmol/pituitary compared to 103 +/- 12 fmol/pituitary for sham-operated control animals. No change of the affinity constant (Ka) was observed (Ka = 1.13 +/- 0.08 X 10(10) M-1; n = 14). Plasma LH increased 5- to 10-fold and FSH-2- to 3-fold after castration, and hypothalamic GnRH content was depleted by 30-60%. Immediate substitution of castrated rats with testosterone propionate (250 micrograms daily) prevented the increases of both plasma gonadotropins and of GnRH-R. Treatment of acutely castrated rats for 7 days with testosterone propionate (50-200 micrograms), 5 alpha-dihydrotestosterone propionate (25-400 micrograms), or estradiol benzoate (2 micrograms) prevented the rise in pit GnRH-R in a dose-related manner and normalized the other parameters studied except that plasma FSH remained slightly elevated. In contrast, when substitutive therapy was started 8 days after castration or later, the 7-day treatment with sex steroids reduced plasma gonadotropins, but pit GnRH-R remained elevated, and hypothalamic GnRH content remained depleted. These results indicate that the marked increase of gonadotropin secretion after castration is mediated at least in part, by an increase in the number of pit GnRH-R. Sex steroids were able to reverse all castration-induced endocrine changes in acutely castrated rats, but in long term castrated animals their action at higher centers to normalize hypothalamic GnRH content, and indirectly, to reduce pit GnRH-R content, was either delayed or ineffective. Thus, the rapid feedback action of sex steroids in long term castrated rats may be predominantly exerted at the pituitary level.
D000818:Animals; D002369:Castration; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000502:physiology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011966:Receptors, LHRH; D013739:Testosterone / Q000494:pharmacology*; D014020:Tissue Extracts
D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D014020:Tissue Extracts; D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone