Stage-Specific Expression of Pituitary Adenylate Cyclase-Activating Polypeptide Type I Receptor Messenger Ribonucleic Acid During Ovarian Follicle Development in the Rat

Expression of pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with considerable homology to vasoactive intestinal peptide, has been shown to be stimulated by gonadotropins in the ovary. The present studies further evaluated the cell-type specific expression and gonadotropin regulation of PACAP type I receptor (PACAPR) messenger RNA in immature rat ovaries and in cultured preovulatory follicles. Northern blot analysis of ovaries ob- tained from prepubertal rats revealed the increased expression of PACAPR during prepubertal development. The major cell types ex- pressing PACAPR messenger RNA were granulosa cells of large pre- antral follicles. Treatment of immature rats with PMSG caused a decrease in ovarian PACAPR expression. In contrast, treatment with human (h) CG at 2 days after PMSG treatment stimulated ovarian PACAPR messenger RNA within 3- 6 h in granulosa cells of preovu- latory follicles. Treatment of cultured preovulatory follicles in vitro with LH further confirmed the time- and dose-dependent stimulation of PACAPR by gonadotropins in granulosa cells of preovulatory fol- licles. Moreover, RNase protection assay revealed that the short vari- ant of ovarian PACAPR was the predominant form stimulated during prepubertal development and by gonadotropins. These results dem- onstrate the expression of PACAPR messenger RNA in granulosa cells of growing follicles and of preovulatory follicles stimulated by gonadotropins, and suggest that PACAP may play a role in the growth of developing follicles and in ovulation as an autocrine/paracrine factor. (Endocrinology 141: 702-709, 2000)