title: Differential in vitro secretion of gonadotropin-releasing hormone (GnRH) and [hydroxyproline]GnRH from the rat hypothalamus during postnatal development.
abstract: The differential secretion of gonadotropin-releasing hormone (GnRH) and [hydroxyproline9]GnRH (HypGnRH) has been recently reported from the adult rat hypothalamus. We report here in vitro cosecretion of HypGnRH and GnRH by the hypothalamus of 2-45 day-old-rats and provide evidence that they are differentially regulated throughout development. The secretion of both forms of GnRH was increased in a dependent manner during depolarization by high K+ solutions, and was stimulated by forskolin and 12-O-tetradecanoylphorbol-13-acetate (TPA), activators of adenylate cyclase and protein kinase C pathways, respectively. The proportion of HypGnRH in the release of GnRH-like peptides remained stable and high (33-40%) under basal and K+-induced conditions until days 13 and 21, respectively. By contrast, the proportion of HypGnRH in the total GnRH-like content of the developing hypothalamus continuously decreased (from 37% to 14%). Similarly, the proportion of HypGnRH: total GnRH-like material released remained stable in TPA- (30%) and forskolin- (50%) induced secretion until postnatal day 8. Evaluation of release over tissue store ratios revealed a 1.3-to 2.8-fold higher release of HypGnRH compared to GnRH according to the different secretions and postnatal periods examined. The preferential recruitment of HypGnRH was maintained under basal and K+ conditions during postnatal development, but it disappeared under TPA stimulation from day 13 onwards. After forskolin stimulation, the preferential mobilization of HypGnRH was markedly reduced from day 2 to day 13 but recovered its high perinatal level during puberty. Taken together, our results support the hypothesis that HypGnRH may play a specific role in development. In addition, a specific function of this peptide taking place during puberty through the activation of the adenylate cyclase pathway is suggested.
authors.affiliation: ICNE, UMR 6544 CNRS, Université de la Méditerranée, Faculté de Médecine Nord, Marseille, France.
authors.forename: L
authors.initials: L
authors.lastname: Rochdi
authors.forename: L
authors.initials: L
authors.lastname: Théraulaz
authors.forename: A
authors.initials: A
authors.lastname: Enjalbert
authors.forename: J P
authors.initials: JP
authors.lastname: Gautron
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism*; D007031:Hypothalamus / Q000254:growth & development* / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D005576:Colforsin; D007987:Gonadotropin-Releasing Hormone; C074293:LHRH, hydroxyprolyl(9)-; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium