title: Mechanisms for PACAP-induced prolactin gene expression in grass carp pituitary cells.
abstract: In mammals, pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic hormone with diverse functions but its role in prolactin (PRL) regulation is highly controversial. To shed light on Prl regulation by PACAP in fish model, grass carp pituitary cells was used as a model to examine the receptor specificity and signal transduction for PACAP modulation ofprlgene expression in the carp pituitary. Using RT-PCR, PACAP-selective PAC1 receptor was detected in carp lactotrophs. In carp pituitary cells, nanomolar doses of PACAP, but not VIP, could elevate Prl secretion and protein production with concurrent rise inprlmRNA and these stimulatory effects were blocked by PACAP antagonist but not VIP antagonist. PACAP-inducedprlmRNA expression could be mimicked by activating adenylate cyclase (AC), increasing cAMP level by cAMP analog, or increasing intracellular Ca2+([Ca2+]i) by Ca2+ionophore/voltage-sensitive Ca2+channel (VSCC) activator. PACAP-inducedprlgene expression, however, was attenuated/abolished by suppressing cAMP production, inhibiting PKA activity, blocking [Ca2+]i mobilization and VSCC activation, calmodulin (CaM) antagonism, and inactivation of JNK and CaM Kinase II (CaMK-II). Similar sensitivity to CaM, JNK, and CaMK-II blockade was also noted by substituting cAMP analog for PACAP as the stimulant forprlmRNA expression. These results, as a whole, provide evidence for the first time that (i) PACAP activation of PAC1 receptor expressed in carp lactotrophs could induce Prl synthesis and secretion, and (ii) Prl production induced by PACAP was mediated by upregulation ofprlgene expression, presumably via functional coupling of cAMP/PKA-, Ca2+/CaM-, and MAPK-dependent cascades.
authors.affiliation: School of Biological SciencesUniversity of Hong Kong, Hong Kong lincy.hkbu@gmail.com olwong@hku.hk.|Clinical DivisionSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong.|YMU-HKBU Joint Laboratory of Traditional Natural MedicineYunnan Minzu University, Kunming, China.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Lin
authors.affiliation: School of Biological SciencesUniversity of Hong Kong, Hong Kong.
authors.forename: Xue
authors.initials: X
authors.lastname: Jiang
authors.affiliation: School of Biological SciencesUniversity of Hong Kong, Hong Kong.
authors.forename: Mulan
authors.initials: M
authors.lastname: He
authors.affiliation: Clinical DivisionSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Clinical DivisionSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Clinical DivisionSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong.|YMU-HKBU Joint Laboratory of Traditional Natural MedicineYunnan Minzu University, Kunming, China.
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Bian
authors.affiliation: School of Biological SciencesUniversity of Hong Kong, Hong Kong lincy.hkbu@gmail.com olwong@hku.hk.
authors.forename: Anderson O L
authors.initials: AO
authors.lastname: Wong
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002347:Carps; D000242:Cyclic AMP / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D052682:Lactotrophs / Q000187:drug effects* / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D011388:Prolactin; D000242:Cyclic AMP; D002118:Calcium
keywords: PAC-I receptor; PACAP; grass carp; pituitary; prolactin; signal transduction