Prolactin releasing peptide (PrRP) stimulates luteinizing hormone (LH) andfollicle stimulating hormone (FSH) via a hypothalamic mechanism in male rats.

Prolactin releasing peptide (PrRP) was originally isolated as an endogenous hypothalamic ligand for the hGR3 orphan receptor. It has been shown to rel ease prolactin from dispersed pituitaries harvested from lactating female r ats and only at very high doses in cycling females. PrRP is reported to hav e no effect on prolactin production from dispersed pituitary cells harveste d from males. The CNS distribution of this peptide suggested a role for PrR P in the control of the hypothalamo-pituitary axis. The aim of this study w as to examine the actions of PrRP (1-31) on circulating pituitary hormones following intracerebroventricular (ICV) injection in male rats and to inves tigate the mechanism of PrRP's effect by measurement of hypothalamic releas ing factors in vitro. In our experiments, PrRP (1-31) did not release LH, F SH, TSH, growth hormone or prolactin directly from dispersed male pituitary cells in vitro. We have shown for the first time that following ICV inject ion of PrRP (1-31) 5 nmol there was a highly significant simulation of plas ma LH that began at 10 minutes and was maintained over the course of the ex periment (at 60 minutes PrRP 5 nmol 2.2+/-0.2 vs. saline 0.5 +/-0.1 ng/ml, p<0.001). Plasma FSH increased at 20 minutes following ICV injection (PrRP 5nmol 10.8+/-2.0 ng/ml vs. saline 5.1+/-0.5, p<0.01). Total plasma testoste rone increased at 60 minutes post injection (PrRP 5nmol 9.2+/-1.6 vs. salin e 3.5+/-0.6 nmol/l, p<0.01). There was no significant alteration in plasma prolactin levels. PrRP significantly increased the release of LHRH from hyp othalamic explants in vitro (PrRP 100nmol/l 180.5+/-34.5% of the basal; sec retion, p<0.05). PrRP (100nmol/l) also increased the following hypothalamic peptides involved in the control of pituitary hormone release, vasoactive intestinal peptide (VIP) 188.1+/-24.6% and galanin 153.8+/-13.0% (both p<0. 001 vs. basal secretion) but had no effect on orexin A secretion. These res ults suggest a role for PrRP in the control of gonadotrophin secretion acti ng via a hypothalamic mechanism involving the release of LHRH.