Effect of recombinant inhibin on gonadotropin secretion during proestrus and estrus in the rat.
This work investigated the ability of recombinant human (rh) inhibin A or the GnRH antagonist [Ac-D2Nal1, delta Cpa2, delta 3Pal3, Arg5 delta 5-(p-methoxyphenyl)5-oxo-2-aminopentanoic acid6, delta Ala10]GnRH to alter plasma immunoreactive LH and FSH levels in cycling female rats. In a first series of experiments, rh inhibin A (25 micrograms/kg) was injected iv between 0800 and 0830 h, or at 0800 and 1200 h, on proestrus, and plasma hormone levels were measured from 1200-1900 h. Both regimens of administration significantly (P less than or equal to 0.01) lowered mean plasma FSH levels but did not mask the primary FSH surge. This treatment also lowered the overall amount of LH released, although the difference between control and inhibin-treated rats only reached statistical significance (P less than or equal to 0.05) after two injections of the protein. Measurement of the number of tubal ova shed on the next estrus showed no difference between rats injected with the vehicle or inhibin at 0830 h. Finally, it was shown that administration of the GnRH antagonist (100 micrograms/kg) at 1200 h interfered with the primary surges of both LH and FSH. In a second series of experiments, rh inhibin A (25 micrograms/kg) was injected once at 2000 h on proestrus. In these animals, inhibin significantly (P less than or equal to 0.01) decreased mean plasma FSH levels between 2000 h on proestrus and 0500 h on estrus and totally suppressed the secondary FSH surge. LH secretion remained low in control animals, and no measurable changes were observed after inhibin treatment. Flushing of the ova 5 days later (i.e. during estrus of the subsequent cycle) showed no difference between control and inhibin-treated rats. Injection of the GnRH antagonist (100 micrograms/kg) at 2000 h on proestrus decreased the total amount of FSH secreted during late proestrus and early estrus. However, FSH secretion showed an increase at between 0100 and 0400 h of estrus despite blockade of GnRH receptors. These results indicate that administration of rh inhibin A interferes with both the primary and secondary FSH surges. In contrast to its inability to alter LH release by ovariectomized rats, inhibin also blunted LH secretion during the afternoon of proestrus. Whether these results represent differential effects of inhibin on LH secreted by intact and gonadectomized animals, or whether the documented changes in pituitary responsiveness to GnRH during proestrus are accompanied by an increased sensitivity to inhibin, needs further investigation.
Rivier
C
C
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Schwall
R
R
Mason
A
A
Burton
L
L
Vale
W
W
D000818:Animals; D002940:Circadian Rhythm; D004971:Estrus / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007265:Inhibins / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D010060:Ovulation / Q000187:drug effects; D011359:Proestrus / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins
D011994:Recombinant Proteins; C065075:LHRH, N-Ac(2)-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-5-(4-methoxyphenyl)-5-oxo-2-aminopentanoic acid(6)-Ala(10)-; D007987:Gonadotropin-Releasing Hormone; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone