title: GnRH decreases adiponectin expression in pituitary gonadotropes via the calcium and PKA pathways.
abstract: As endocrinologically active cells, adipocytes are capable of secreting various adipocytokines such as leptin, resistin, and adiponectin to impact metabolic function. Although adipocytes remain to be the primary site of synthesis and secretion, there is now growing evidence that supports the presence of adiponectin and its receptors within the hypothalamic-pituitary-gonadal axis, providing a possible link between obesity and abnormal reproductive physiology. It has been demonstrated that adiponectin may reduce gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus as well as modulate gonadal steroid hormone production. Furthermore, prior data indicate that adiponectin may play a role in decreasing luteinizing hormone secretion from pituitary gonadotropes. We aimed to identify the hormonal regulators of adiponectin and its receptors, AdipoR1 and AdipoR2, in pituitary gonadotropes using immortalized gonadotropic LβT2 cells and primary rat pituitary cells. Our study shows significant alterations in adiponectin expression across the estrous cycle. In addition, we present a novel finding that GnRH suppresses pituitary adiponectin expression via the calcium and protein kinase A intracellular pathways in both cultured rat primary pituitary cells and the LβT2 gonadotrope cell line. The GnRH did not alter expression of the adiponectin receptors, AdipoR1 and AdipoR2, in cultured gonadotropes. Expression of the adiponectin receptors, AdipoR1 and AdipoR2, was not altered by GnRH in cell culture but in vivo or in vitro. Our data suggest that gonadotrope function may be modulated by GnRH-mediated changes in adiponectin expression.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. Joanthan.Kim@UTSouthwestern.edu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kim
authors.forename: Weiming
authors.initials: W
authors.lastname: Zheng
authors.forename: Constance
authors.initials: C
authors.lastname: Grafer
authors.forename: Merry Lynn
authors.initials: ML
authors.lastname: Mann
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Halvorson
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015536:Down-Regulation; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D008297:Male; D051379:Mice; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin / Q000378:metabolism; D012737:Sex Factors; D013997:Time Factors
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; C499920:Adipoq protein, rat; D020536:Enzyme Activators; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; C504339:adiponectin receptor 1, rat; C475421:adiponectin receptor 2, mouse; C506573:adiponectin receptor 2, rat; D007987:Gonadotropin-Releasing Hormone; D017868:Cyclic AMP-Dependent Protein Kinases