title: Melatonin regulates somatotrope and lactotrope function through common and distinct signaling pathways in cultured primary pituitary cells from female primates.
abstract: Melatonin (MT) is secreted by the pineal gland and exhibits a striking circadian rhythm in its release. Depending on the species studied, some pituitary hormones also display marked circadian/seasonal patterns and rhythms of secretion. However, the precise relationship between MT and pituitary function remains controversial, and studies focusing on the direct role of MT in normal pituitary cells are limited to nonprimate species. Here, adult normal primate (baboons) primary pituitary cell cultures were used to determine the direct impact of MT on the functioning of all pituitary cell types from the pars distalis. MT increased GH and prolactin (PRL) expression/release in a dose- and time-dependent fashion, a response that was blocked by somatostatin. However, MT did not significantly affect ACTH, FSH, LH, or TSH expression/release. MT did not alter GHRH- or ghrelin-induced GH and/or PRL secretions, suggesting that MT may activate similar signaling pathways as ghrelin/GHRH. The effects of MT on GH/PRL release, which are likely mediated through MT1 receptor, involve both common (adenylyl cyclase/protein kinase A/extracellular calcium-channels) and distinct (phospholipase C/intracellular calcium-channels) signaling pathways. Actions of MT on pituitary cells also included regulation of the expression of other key components for the control of somatotrope/lactotrope function (GHRH, ghrelin, and somatostatin receptors). These results show, for the first time in a primate model, that MT directly regulates somatotrope/lactotrope function, thereby lending support to the notion that the actions of MT on these cells might substantially contribute to the define daily patterns of GH and PRL observed in primates and perhaps in humans.
authors.affiliation: Department of Cell Biology, Physiology, and Immunology (A.I.-C., J.C.-C., M.D.G., J.P.C., R.M.L.), University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofia; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición; and Campus de Excelencia Internacional Agroalimentario (ceiA3), E-14014 Córdoba, Spain; and Department of Medicine (J.C.-C., R.D.K.), Section of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago and Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois 60612.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ibáñez-Costa
authors.forename: José
authors.initials: J
authors.lastname: Córdoba-Chacón
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Gahete
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Kineman
authors.forename: Justo P
authors.initials: JP
authors.lastname: Castaño
authors.forename: Raúl M
authors.initials: RM
authors.lastname: Luque
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000235:genetics / Q000378:metabolism; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D052682:Lactotrophs / Q000502:physiology*; D008550:Melatonin / Q000378:metabolism*; D010215:Papio; D010902:Pituitary Gland / Q000166:cytology* / Q000502:physiology; D011388:Prolactin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism; D052683:Somatotrophs / Q000502:physiology*
chemical_list: D054439:Ghrelin; D013004:Somatostatin; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D008550:Melatonin