The gene which encodes growth hormone releasing hormone (GHRH) arose from an ancestral gene that also gave rise to the genes for vasoactive intestinal peptide (VIP), pituitary adenylyl-cyclase activating polypeptide (PACAP), glucagon, and secretin. Review of the GHRH gene sequence predicts a second 30 amino acid carboxyl terminal peptide product that has a high degree of homology with VIP and PACAP. This novel peptide, which we have called GHRH-related peptide (GHRH-RP), has been previously localized to rat testicular germ cells. GHRH-RP activates Sertoli cell expression of stem cell factor. Although GHRH is produced by a variety of rat tissues, including the hypothalamus, placenta, testis, and ovary, GHRH-RP has only been described in the testis. We sought to determine if this novel peptide is present in the cycling rat ovary.

Using reverse transcriptase-polymerase chain reaction (RT-PCR), we confirmed that a GHRH transcript is present in rat ovary. RNA was isolated from separated ovarian cell types (interstitial cells, granulosa cells, and corpora lutea) from young female rats. By RT-PCR, each of these cell types expressed similar levels of GHRH mRNA. Immunohistochemical analyses of sections from cycling rat ovaries using rabbit GHRH-RP antisera revealed abundant GHRH-RP immunoactivity in ovarian corporal luteal cells and oocytes, as compared to controls. Interestingly, granulosa cells were not immunoreactive.

We conclude that the novel peptide GHRH-RP is produced in ovary where it is localized to oocytes and corpora lutea. These results are analogous to the germ cell distribution of GHRH-RP immunoactivity in rat testes and lead us to speculate that GHRH-RP may play a role as a paracrine factor in reproductive tissues.