Journal of Korean Endocrine Society 2004;19(2):152-164.
Published online April 1, 2004.
Regulation of Prolactin Gene Expression by Hypothalamic Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in the Female Rat Pituitary Gland.
Young Il Kim, Tae Young Ha, Eun Sook Kim, Il Seong Nam-Goong, M S O'Dorisio, Min Kyu Hur, Sang Kyu Park
1Department of Internal Medicine, Ulsan University Hospital, Ulsan, South Korea.
2Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
3Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
4Department of Pediatrics, College of Medicine3, University of Ulsan, Ulsan, South Korea.
Abstract
BACKGROUND
Pituitary adenylate cyclase-activating polypeptide (PACAP) plays the role of a hypophysiotropic factor, which regulates the synthesis and secretion of pituitary hormones through the hypothalamo-hypophysial portal system. No clear evidence has yet been reported regarding the regulation of prolactin (PRL) by PACAP. In the present study, we tested a hypothesis that PACAP regulates the synthetic machinery of PRL during the estrus cycle and pubertal process using intracerebroventricular (i.c.v.) injection of an antisense oligodeoxynucleotide (ODN) against type I PACAP receptor (PAC1). METHODS: An RNase protection assay (RPA) was used to determine the pattern of hypothalamic PACAP and PAC1 mRNA expressions during the estrus cycle. Antisense PAC1 ODN was administered via i.c.v. injection to the female rats in normal estrus cycle of pubertal process. Northern blot analysis was used to determine the mRNA ievel of PRL in the pituitary gland. RESULTS: 1) PACAP mRNA in the medial basal hypothalamus was significantly increased at the diestrus I, while PAC1 mRNA showed no significant change. 2) PRL mRNA level of pituitary was increased by an injection of antisense PAC1 ODN at the proestrus and estrus stages. 3) PRL mRNA level of pituitary was significantly decreased by antisense PAC1 ODN injection at stage of prepuberty and initiate puberty, while its level was increased at stage of puberty. CONCLUSION: These data suggest that PACAP suppresses PRL mRNA synthesis through the PAC1 signaling pathway in the certain estrus cycle environments. It may be also involved in the regulation of pituitary PRL gene expression during the pubertal process
Key Words: PACAP, PACAP receptor type l (PAC1), Antisense PAC1 Oligodeoxynucleotide, Prolactin, Female puberty
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