EFFECTS OF GROWTH-HORMONE SECRETAGOGUES ON PROLACTIN-RELEASE IN ANESTHETIZED DWARF (DW DW) RATS/

In addition to stimulating GH release, GH secretagogues such as GH-rel easing peptide-6 (GHRP-6) stimulate small amounts of ACTH and PRL rele ase. Although the effects on ACTH have recently been studied, there is little information about the effects of GHRP-6 on PRL. We have now st udied GHRP-6-induced GH and PRL release and their regulation by estrog en (E-2,) in anesthetized male and female rats and in GH-deficient dwa rf(dw/dw) rats that maintain high pituitary PRL stores and show elevat ed hypothalamic GH secretagogue receptor expression. Whereas GHRP-6 (0 .1-2.5 mu g, iv) did not induce PRL release in normal male or female r ats, significant PRL responses were observed in dw/dw females. These r esponses were abolished by ovariectomy and could be strongly induced i n male dw/dw rats by E-2 treatment. These effects could be dissociated from GHRP-6-induced GH release in the same animals, but not from PRL release induced by TRH, which was also abolished by ovariectomy and in duced in males by E-2, treatment. However, the effects of GHRP-6 on PR L were unlikely to be mediated by TRH because in the same animals, TSH levels were unaffected by GHRP-6 whereas they were increased by TRH. The increased PRL response could reflect an increase in GH secretagogu e receptor expression that was observed in the arcuate and ventromedia l nuclei of E-2-treated rats. Our results suggest that the minimal PRL -releasing activity of GHRP-6 in normal rats becomes prominent in GH-d eficient female dw/dw rats and is probably exerted directly at the pit uitary; these GHRP-6 actions may be modulated by E-2, at both hypothal amic and pituitary sites.