title: Possible involvement of PACAP and PACAP type 1 receptor in GnRH-induced FSH β-subunit gene expression.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kanasaki
authors.forename: Indri N
authors.initials: IN
authors.lastname: Purwana
authors.forename: Tselmeg
authors.initials: T
authors.lastname: Mijiddorj
authors.forename: Aki
authors.initials: A
authors.lastname: Oride
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D002460:Cell Line; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000235:genetics* / Q000378:metabolism
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix