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Endocrinology Vol. 141, No. 5 1909-1912
Copyright © 2000 by The Endocrine Society


ARTICLES

Prolactin Releasing Peptide (PrRP) Stimulates Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) via a Hypothalamic Mechanism in Male Rats

L. J. Seal, C. J. Small, M. S. Kim, S. A. Stanley, S. Taheri, M. A. Ghatei and S. R. Bloom

Endocrine Unit, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, United Kingdom

Address all correspondence and requests for reprints to: Stephen R. Bloom, M.D., Imperial College at Hammersmit Campus, Du Cane Road, 6th Floor Commonwealth Building, Division of Investigative Science, London, United Kingdom W12 0NN.

Prolactin releasing peptide (PrRP) was originally isolated as an endogenous hypothalamic ligand for the hGR3 orphan receptor. It has been shown to release prolactin from dispersed pituitaries harvested from lactating female rats and only at very high doses in cycling females. PrRP is reported to have no effect on prolactin production from dispersed pituitary cells harvested from males. The CNS distribution of this peptide suggested a role for PrRP in the control of the hypothalamo-pituitary axis. The aim of this study was to examine the actions of PrRP (1–31) on circulating pituitary hormones following intracerebroventricular (ICV) injection in male rats and to investigate the mechanism of PrRP’s effect by measurement of hypothalamic releasing factors in vitro. In our experiments, PrRP (1–31) did not release LH, FSH, TSH, growth hormone or prolactin directly from dispersed male pituitary cells in vitro. We have shown for the first time that following ICV injection of PrRP (1–31) 5 nmol there was a highly significant simulation of plasma LH that began at 10 minutes and was maintained over the course of the experiment (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 5 nmol 10.8 ± 2.0 ng/ml vs. saline 5.1 ± 0.5, p < 0.01). Total plasma testosterone increased at 60 minutes post injection (PrRP 5 nmol 9.2 ± 1.6 vs. saline 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 hypothalamic explants in vitro (PrRP 100 nmol/l 180.5 ± 34.5% of the basal secretion, p < 0.05). PrRP (100 nmol/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 results suggest a role for PrRP in the control of gonadotrophin secretion acting via a hypothalamic mechanism involving the release of LHRH.




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