This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rabadan-Diehl, C. Articles by Aguilera, G. Search for Related Content PubMed PubMed Citation Articles by Rabadan-Diehl, C. Articles by Aguilera, G.

Glucocorticoids Increase Vasopressin V1b Receptor Coupling to Phospholipase C

Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Cristina Rabadan-Diehl, Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10N262, 10 Center Drive MSC 1862, Bethesda, Maryland 20892-1862. E-mail: rabadanc{at}cc1.nichd.nih.gov

Vasopressin (VP) stimulates pituitary ACTH secretion after binding to V1b VP receptors (V1b-R) coupled to phospholipase C (PLC). This effect of VP on ACTH secretion, unlike that of CRH, is resistant to glucocorticoid feedback. To determine whether changes in V1b-R expression or signaling mediate the refractoriness to glucocorticoids, the effects of glucocorticoids on pituitary VP binding, V1b-R messenger RNA (mRNA) and VP-stimulated inositol phosphate (IP) formation were studied in vivo and in vitro in the rat. Dexamethasone injection for 7 days decreased VP binding but increased V1b-R mRNA, indicating that mRNA levels do not reflect receptor number. In spite of the binding loss, VP-stimulated IP formation was enhanced in dexamethasone-treated rats, suggesting that glucocorticoids increase the coupling efficiency of the V1b receptor to phospholipase C. Pretreatment of pituitary cells in vitro with dexamethasone or corticosterone, also potentiated IP formation by low and high doses of VP, indicating that glucocorticoids act directly in the pituitary and not through changes in hypothalamic factors. The effect is mediated by glucocorticoid receptors because it was blocked by glucocorticoid but not mineralocorticoid antagonists. Dexamethasone potentiated the stimulation of IP by other PLC-dependent ligands (GnRH, TRH) but not that by the calcium ionophore, ionomycin, suggesting a site of action between the receptor and PLC. After treatment with dexamethasone, in vivo or in vitro, Western blot analysis revealed marked increases in the GTP binding protein, G_q, which may account for the potentiating effect of glucocorticoid on ligand-stimulated IP. The data demonstrate that glucocorticoids increase coupling of the V1b-R with PLC thereby providing a mechanism by which VP facilitates corticotroph responsiveness in spite of elevated levels of plasma glucocorticoids during stress.

This article has been cited by other articles:

				E. L. Dempster, I. Burcescu, K. Wigg, E. Kiss, I. Baji, J. Gadoros, Z. Tamas, J. L. Kennedy, A. Vetro, M. Kovacs, et al. Evidence of an Association Between the Vasopressin V1b Receptor Gene (AVPR1B) and Childhood-Onset Mood Disorders Arch Gen Psychiatry, October 1, 2007; 64(10): 1189 - 1195. [Abstract] [Full Text] [PDF]

				L. C. Carey, S. B. Tatter, and J. C. Rose Ontogeny and Effects of Hypothalamic Pituitary Disconnection on Formation of Inositol Trisphosphate in Fetal Sheep Pituitary Cells Endocrinology, March 1, 2007; 148(3): 1440 - 1444. [Abstract] [Full Text] [PDF]

				H. S. Kim, S. Yumkham, J. H. Choi, G. H. Son, K. Kim, S. H. Ryu, and P.-G. Suh Serotonin stimulates GnRH secretion through the c-Src-PLC {gamma}1 pathway in GT1-7 hypothalamic cells. J. Endocrinol., September 1, 2006; 190(3): 581 - 591. [Abstract] [Full Text] [PDF]

				G.-S. Lee, K.-C. Choi, and E.-B. Jeung Glucocorticoids differentially regulate expression of duodenal and renal calbindin-D9k through glucocorticoid receptor-mediated pathway in mouse model Am J Physiol Endocrinol Metab, February 1, 2006; 290(2): E299 - E307. [Abstract] [Full Text] [PDF]

				S. Ma, M. J. Shipston, D. Morilak, and J. A. Russell Reduced Hypothalamic Vasopressin Secretion Underlies Attenuated Adrenocorticotropin Stress Responses in Pregnant Rats Endocrinology, March 1, 2005; 146(3): 1626 - 1637. [Abstract] [Full Text] [PDF]

				S. F. Young, S. B. Tatter, N. K. Valego, J. P. Figueroa, J. Thompson, and J. C. Rose The role of hypothalamic input on corticotroph maturation in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1621 - R1630. [Abstract] [Full Text] [PDF]

				S. F. Young, J. L. Smith, J. P. Figueroa, and J. C. Rose Ontogeny and effect of cortisol on vasopressin-1b receptor expression in anterior pituitaries of fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2003; 284(1): R51 - R56. [Abstract] [Full Text] [PDF]

				S. F. Young and J. C. Rose Attenuation of Corticotropin-Releasing Hormone and Arginine Vasopressin Responsiveness During Late-Gestation Pregnancy in Sheep Biol Reprod, June 1, 2002; 66(6): 1805 - 1812. [Abstract] [Full Text] [PDF]

				R. Cheung and J. Mitchell Mechanisms of regulation of G11alpha protein by dexamethasone in osteoblastic UMR 106-01 cells Am J Physiol Endocrinol Metab, January 1, 2002; 282(1): E24 - E30. [Abstract] [Full Text] [PDF]

				A. Nomura, Y. Iwasaki, M. Saito, Y. Aoki, E. Yamamori, N. Ozaki, K. Tachikawa, N. Mutsuga, M. Morishita, M. Yoshida, et al. Involvement of upstream open reading frames in regulation of rat V1b vasopressin receptor expression Am J Physiol Endocrinol Metab, May 1, 2001; 280(5): E780 - E787. [Abstract] [Full Text] [PDF]

				A. Lacroix, N. N'Diaye, J. Tremblay, and P. Hamet Ectopic and Abnormal Hormone Receptors in Adrenal Cushing's Syndrome Endocr. Rev., February 1, 2001; 22(1): 75 - 110. [Abstract] [Full Text]