Possible involvement of PACAP and PACAP type 1 receptor in GnRH-induced FSH β-subunit gene expression.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor, PACAP type 1 receptor (PAC1-R) play an important role in the induction of pituitary gonadotropins. In this present study, we examined whether the PAC1-R was involved in the action of gonadotropin-releasing hormone (GnRH) on gonadotropin FSHβ subunit expression. In a static culture, GnRH stimulation significantly increased PAC1-R expression as well as PACAP gene expression in the gonadotroph cell line, LβT2. Stimulation with low frequency GnRH pulses, which preferentially increase FSHβ, increased the expression of both the PAC1-R and the PACAP genes to a greater extent than did high frequency pulses. In the determination of transcriptional activity, the GnRH antagonist, cetrotide inhibited GnRH-induced FSHβ promoter activity completely, but PACAP6-38, a PACAP antagonist, had no effect on GnRH-induced FSHβ promoter activity. As expected, PACAP-induced FSHβ promoter activity was significantly prevented by PACAP6-38, but was not affected by cetrotide. PACAP6-38, however, significantly prevented GnRH-increased FSHβ mRNA expression. These observations suggest that GnRH-induced FSHβ gene expression is stimulated partially through PAC1-R by gonadotrophs producing PACAP or PAC1-R.