Induction of the gonadotrophin surge-inhibiting factor by FSH and its elimination: a sex difference in the efficacy of the priming effect of gonadotrophin-releasing hormone on the rat pituitary gland.
This study was designed to explore the efficacy of gonadotrophin-releasing hormone (GnRH) to antagonize the effect of gonadotrophin surge-inhibiting factor (GnSIF) on the timing of the induction by GnRH of the maximal self-priming effect on pituitary LH responsiveness. The GnSIF levels were increased by FSH treatment and reduced after gonadectomy. Female rats were injected s.c. with 10 IU FSH or saline (control) on three occasions during the 4-day cycle. Serial i.v. injections of GnRH (500 pmol/kg body weight) were administered to intact rats on the afternoon of pro-oestrus or 15-30 min after ovariectomy. Intact male rats were given 10 IU FSH and 500 or 2000 pmol GnRH/kg body weight on an equivalent time-schedule. Endogenous GnRH release was suppressed with phenobarbital. In intact female control rats, the timing of the maximally primed LH response was delayed as the GnRH pulse-interval increased. FSH treatment of female rats induced a suppression of the initial unprimed LH response and delayed the maximally primed LH response, which showed further delay as the GnRH pulse-interval was increased. When the pulsatile administration of GnRH was started 15-30 min after ovariectomy, the priming effect of GnRH did not change as the GnRH pulse-interval was increased in the saline-treated rats. However, FSH treatment caused a suppression of the unprimed LH response, a delay in the primed LH response and decreased the delay of the maximally primed LH response to GnRH when the GnRH pulse-interval was decreased. Increasing the interval between ovariectomy and the first GnRH pulse to 4 h diminished the efficacy of the FSH treatment: GnRH-induced priming was delayed by only one pulse instead of the two pulses in control rats. In intact males but not in orchidectomized rats, a self-priming effect was demonstrated during GnRH pulses which were 1 h apart. The effect of 2 nmol GnRH/kg body weight was the most pronounced. Compared with intact female rats, the timing of the maximally primed LH response was delayed by 1 h. FSH treatment did not affect the pituitary LH response to both dose levels of GnRH. It is concluded that FSH treatment increased the release of GnSIF by the ovary, then induced a state of low responsiveness of the pituitary gland to GnRH and subsequently delayed GnRH-induced maximal self-priming. The efficacy of GnRH to prime the pituitary gland was higher when GnSIF levels were decreasing after removal of the ovaries.(ABSTRACT TRUNCATED AT 400 WORDS)
Koppenaal
D W
DW
Division of Medical Pharmacology of the Leiden/Amsterdam Center for Drug Research, University of Leiden, Sylvius Laboratory, The Netherlands.
van Dieten
J A
JA
Tijssen
A M
AM
de Koning
J
J
D000818:Animals; D003864:Depression, Chemical; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D042341:Gonadal Hormones; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013997:Time Factors
D042341:Gonadal Hormones; D011506:Proteins; C080538:attenuin; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone