GALANIN - A NAVEL INTRAOVARIAN REGULATORY PEPTIDE

Galanin is a 29-amino acid peptide that acts as a neuropeptide in many tissues. To date, galanin action and the hormonal regulation of galan in gene expression have not been described in the ovary of any species . To study possible ovarian expression and regulation of galanin, imma ture gonadotropin-primed rats were given hCG (10 IU), and their ovarie s were collected 0, 4, 8, 12, and 20 h after hCG treatment for determi nation of galanin messenger RNA (mRNA) concentration by solution hybri dization. Galanin mRNA levels progressively increased after hCG admini stration, peaking at 12 h (2.4-fold increase vs. 0 h), with a subseque nt return to 0 h levels at 20 h. To determine a possible ovarian role for galanin, rats were killed 48 h after gonadotropin administration, their ovaries were removed, and granulosa cells were harvested. These cells and the ovarian tissue remaining after granulosa cell collection (i.e, ''shells'') were each cultured for 24 h with increasing concent rations of galanin (0, 10, 100, and 1000 nM) in the presence or absenc e of LH. The medium was examined for steroid production and metallopro teinase inhibitor activity. In granulosa cell cultures, galanin increa sed the levels of estradiol by 26% and had no effect on progesterone, but decreased metalloproteinase inhibitor activity by 61% in the condi tioned medium. In the shell cultures, galanin increased estradiol, pro gesterone, and androstenedione in the medium, suggesting that galanin acts on cells other than granulosa cells or that galanin action requir es a paracrine interaction between granulosa and thecal cells. Our dat a demonstrate that galanin message is increased by hCG, and that galan in acts to amplify ovarian steroidogenesis while decreasing metallopro teinase inhibitor activity. These findings establish that ovarian gala nin mRNA is hormonally stimulated and that galanin acts as an intraova rian regulatory peptide.