A single injection of gonadotrophin-releasing hormone (GnRH) (60 ng s.c., 42·9 nmol) induced biphasic GnRH receptor regulation in normal intact adult female mice. A transient 22% receptor decrease occurred 30–60 min after injection of GnRH when peak serum decapeptide concentrations were reached (137 ± 41 (s.e.m.) ng/l). This GnRH receptor decrease occurred shortly after the peak serum LH values at 15–30 min. The subsequent rapid (within 1 h) return of GnRH receptor levels to normal suggested transient receptor occupancy by GnRH rather than true receptor loss. At 8 h after injection of GnRH a significant 35% increase in GnRH receptors was consistently observed, when serum GnRH levels were undetectable and serum LH had returned to basal levels. This receptor increase was not due to increased receptor affinity, and was prevented by a non-specific protein synthesis inhibitor.
Ovariectomy, which caused a 50% fall in GnRH receptors (59·4 ± 4·9 fmol/pituitary gland in intact controls; 26·9 ± 2·6 in ovariectomized mice) abolished the induction by GnRH of its own receptors, although the initial transient decrease occurred over the period of the acute serum LH and FSH rise. Despite a 50% reduction in GnRH receptors in ovariectomized mice, increased serum gonadotrophin levels and responsiveness to GnRH were maintained, indicating dissociation between receptor changes and gonadotrophin levels.
No GnRH receptor up-regulation was observed 8 h after a single GnRH injection (60 ng s.c.) in either intact or orchidectomized normal male mice. However, the same treatment doubled GnRH receptors in GnRH-deficient (hpg) female mice.
While GnRH appears to up-regulate its own receptors by a direct action on pituitary gonadotrophs in the GnRH-deficient mouse its action in the normal female mouse pituitary appears secondary to stimulation of a gonadal product, presumably oestrogens.