EVIDENCE FOR SHORT OR ULTRASHORT LOOP NEGATIVE FEEDBACK OF GONADOTROPIN-RELEASING-HORMONE SECRETION

The present studies tested the hypothesis that either short or ultrash ort loop negative feedback regulation of gonadotropin-releasing hormon e (GnRH) secretion occurs in the ewe. As part of ongoing studies inves tigating the regulation of follicle-stimulating-hormone secretion, we obtained the unexpected result that a GnRH antagonist (Nal-Glu) may st imulate GnRH secretion. In that experiment, hypophyseal portal blood w as collected from five short-term ovariectomized ewes at 5-min interva ls for 6 h before and 6 h after intravenous injection of Nal-Glu (10 m u g/kg body weight). An increase in GnRH pulse frequency in associatio n with the blockade of luteinizing hormone (LH) release was evident in 3 of the 5 animals. To determine if an effect of Nal-Glu on episodic GnRH secretion would be more evident in an animal model in which low-f requency pulses of GnRH prevail, the study was repeated in six ewes in the midluteal phase of the estrous cycle and six ovariectomized ewes bearing estradiol and progesterone implants to suppress GnRH release ( artificial luteal model). In luteal-phase ewes, administration of Nal- Glu was followed by an increase in GnRH pulse frequency, pulse size an d the secretion of GnRH between pulses, and by a blockade of LH releas e. In ovariectomized ewes treated with estradiol and progesterone, Nal -Glu administration also stimulated GnRH and inhibited LH secretion. O ur finding that the GnRH antagonist stimulated GnRH secretion is consi stent with the hypothesis that endogenous GnRH may influence its own r elease via either a short or ultrashort loop feedback mechanism.