Effect of recombinant human inhibin on gonadotropin secretion by the male rat.
We have examined the effect of recombinant human inhibin-A on basal and GnRH-induced gonadotropin secretion by male rats or cultured anterior pituitary cells. Inhibin, administered sc 6 h before the experiment, induced dose- and time-related decreases in plasma FSH, but not LH, levels in both intact and castrated male rats. Inhibin also significantly interfered with the in vivo stimulatory effect of 20-500 ng GnRH on FSH release, but had inconsistent and usually modest effects on the LH response. While exposure of cultured pituitary cells to inhibin for 72 h has been reported to interfere with GnRH-induced gonadotropin release, we examined here the effects of shorter exposure periods relevant to in vivo experiments. Exposure of the cells to inhibin (31.3-312.5 pM) for 2-6 h measurably (P less than or equal to 0.01) decreased the ability of 10 nM GnRH to stimulate both FSH and LH released by cultured cells. In contrast, lower (3.1 and 9.4 pM) doses of inhibin had little or no effect. Longer exposures to inhibin (10, 24, and 72 h) increased the inhibitory effect of 31.3-312.5 pM inhibin, while 3.1 and 9.4 pM remained ineffective at all times. These results indicate that exposure of the male rat to inhibin for 6 h decreases FSH secretion, and that this effect is at least partially mediated through blunting of the pituitary response to GnRH. In contrast, the ability of inhibin to interfere with LH release, which is readily apparent in cultured pituitary cells, appears to be of lesser importance in the intact male rat.
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
C
C
Rivier
A
A
Corrigan
W
W
Vale
D000818:Animals; D002369:Castration; D002478:Cells, Cultured; D004347:Drug Interactions; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007265:Inhibins / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D012016:Reference Values; D012727:Sex Characteristics
D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone