School of Chinese Medicine
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 of prl gene 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 in prl mRNA and these stimulatory effects were blocked by PACAP antagonist but not VIP antagonist. PACAP-induced prl mRNA 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-induced prlgene 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 for prlmRNA 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 of prl gene expression, presumably via functional coupling of cAMP/PKA-, Ca2+/CaM-, and MAPK-dependent cascades.
prolactin, PACAP, PAC-I receptor, signal transduction, pituitary, grass carp
Source Publication Title
Journal of Endocrinology
Disclaimer: this is not the definitive version of record of this article.This manuscript has been accepted for publication in Journal of Endocrinology, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at http://dx.doi.org/10.1530/JOE-16-0433, published in 2017.
The project was supported by GRF grants (17128215, 781113, and 780312) and NSFC/RGC joint grant (N_HKU 732/12) from Research Grant Council (HK), HMRF Grant (13142591) from Food and Health Bureau (HKSAR) (to A O L W), and NSFC grant (31660335) from National Natural Science Foundation of China (to C L). Financial support to C L and J X from the School of Biological Sciences (University of Hong Kong) is also acknowledged.
Link to Publisher's Edition
Lin, C., Jiang, X., He, M., Zhao, L., Huang, T., Bian, Z., & Wong, A. (2017). Mechanisms for PACAP-induced prolactin gene expression in grass carp pituitary cells. Journal of Endocrinology, 233 (1), 37-51. https://doi.org/10.1530/JOE-16-0433