title: Developmental changes in pituitary adenylate cyclase activating polypeptide expression during the perinatal period: possible role in fetal gonadotroph regulation.
abstract: Normal reproductive functioning may require secretion of LH independently of FSH. Variation in GnRH pulse frequency and inhibin negative feedback are mechanisms for differential gonadotropin regulation; however, the first instance of differential regulation in rats is during fetal development, prior to the establishment of GnRH connections, when LH accumulates appreciably 2-4 d prior to FSH. Pituitary adenylate cyclase activating polypeptide (PACAP) can differentially regulate the gonadotropins in vitro by stimulating alpha-subunit transcription, lengthening LHbeta transcripts and decreasing FSHbeta mRNA levels, probably through stimulation of follistatin transcription. These experiments are the first to examine whether PACAP influences gonadotroph function in perinatal pituitaries. In vivo, pituitary PACAP mRNA and peptide levels were high at embryonic d 19 and declined by 94 and 85%, respectively, after parturition. This was accompanied by a decrease of 65 and 96% in total follistatin and follistatin-288 mRNAs. These changes were temporally associated with a 20- and 6.5-fold rise in FSHbeta and GnRH receptor mRNAs, respectively, with no significant increase in LHbeta mRNA. In pituitary cell cultures from fetal and postnatal male rats, PACAP mRNA levels were likewise highest in fetal cultures in which the PACAP 6-38 antagonist decreased alpha-subunit and increased FSHbeta mRNA. PACAP 6-38 also reduced basal and GnRH-stimulated LH secretion with little effect on FSH. These data support the hypothesis that PACAP expressed at high levels in the fetal pituitary stimulates alpha-subunit expression and LH secretion and restrains FSH synthesis relative to LH and that a decline in PACAP allows for the neonatal rise in FSH and GnRH receptor because follistatin is decreased.
authors: Department of Anatomical Sciences, ivision of Endocrinology and Metabolism, University of Louisville, School of Medicine, Louisville, Kentucky 40292, USA. jpmoor03@louisville.edu
authors: Joseph P
authors: JP
authors: Moore
authors: Betty C
authors: BC
authors: Villafuerte
authors: Christian A
authors: CA
authors: Unick
authors: Stephen J
authors: SJ
authors: Winters
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005260:Female; D047109:Fetal Development; D038681:Follistatin / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D008297:Male; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010902:Pituitary Gland / Q000196:embryology / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011966:Receptors, LHRH / Q000378:metabolism
chemical_list: D038681:Follistatin; D006065:Gonadotropins, Pituitary; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone