HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0139v1 200/2/223    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Seasholtz, A. Articles by Thompson, R. Search for Related Content PubMed PubMed Citation Articles by Seasholtz, A. Articles by Thompson, R.

A Seasholtz, Mol. & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, 48109-2200, United States
M Ohman, Psychiatry, University of Michigan, Ann Arbor, United States
A Wardani, Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, United States
R Thompson, Psychiatry, University of Michigan, Ann Arbor, United States

Correspondence: Audrey Seasholtz, Email: aseashol{at}umich.edu

Abstract

Corticotropin-releasing hormone (CRH) is a key regulator of the mammalian stress response, mediating a wide variety of stress-associated behaviors including stress-induced inhibition of reproductive function. To investigate the potential direct action of CRH on pituitary gonadotrope function, we examined CRH receptor expression and second messenger signaling in alphaT3-1 cells, a murine gonadotrope-like cell line. Reverse transcriptase-polymerase chain reaction (RT-PCR) studies demonstrate that alphaT3-1 cells express mRNA for the two CRH receptor subtypes, CRH-R1 and CRH-R2, with CRH-R2alpha as the predominant CRH-R2 isoform. Stimulation of the cells with CRH or urocortin (UCN1) results in rapid, transient increases in the intracellular levels of cAMP that are completely blocked by addition of alpha-helical CRH 9-41 or astressin, non-selective CRH receptor antagonists. Stimulation of the cells with CRH-R2 specific ligands, urocortin II (UCN2) or urocortin III (UCN3), results in rapid increases in intracellular cAMP levels to 50-60% of the levels observed with UCN1. Treatment with a selective CRH-R2 antagonist, antisauvagine, completely blocks UCN3-mediated increases in cAMP and significantly reduces, but does not completely block UCN1-mediated increases in cAMP, demonstrating that both CRH-R1 and CRH-R2 are functionally active in these gonadotrope-like cells. Finally, UCN treatment significantly increases the transcriptional activity of the glycoprotein hormone alpha-subunit promoter as assessed by alpha-luciferase transfection assays. Together, these results demonstrate the functional signaling of CRH receptors in alphaT3-1 cells, suggesting that CRH may also modulate pituitary gonadotrope function in vivo.

This article has been cited by other articles:

				R. T. Evans and A. F. Seasholtz Soluble Corticotropin-Releasing Hormone Receptor 2{alpha} Splice Variant Is Efficiently Translated But Not Trafficked for Secretion Endocrinology, September 1, 2009; 150(9): 4191 - 4202. [Abstract] [Full Text] [PDF]