HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 41, 30967-30978, October 13, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/41/30967    most recent M606486200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ruf, F. Articles by Sealfon, S. C. Search for Related Content PubMed PubMed Citation Articles by Ruf, F. Articles by Sealfon, S. C. Social Bookmarking                      What's this?

Mixed Analog/Digital Gonadotrope Biosynthetic Response to Gonadotropin-releasing Hormone^*

Frederique Ruf, Myung-June Park, Fernand Hayot, Gang Lin^¶, Badrinath Roysam^¶, Yongchao Ge, and Stuart C. Sealfon¹

From the Department of Neurology and Center for Translational Systems Biology, Mount Sinai School of Medicine, New York, New York 10029 and the ^¶Department of Electrical, Computer, and Systems Engineering at Rensselaer Polytechnic Institute, Troy, New York 12180

Mammalian reproduction requires gonadotropin-releasing hormone (GnRH)-mediated signaling from brain neurons to pituitary gonadotropes. Because the pulses of released GnRH vary greatly in amplitude, we studied the biosynthetic response of the gonadotrope to varying GnRH concentrations, focusing on extracellular-regulated kinase (ERK) phosphorylation and egr1 mRNA and protein production. The overall average level of ERK activation in populations of cells increased non-cooperatively with increasing GnRH and did not show evidence of either ultrasensitivity or bistability. However, automated image analysis of single-cell responses showed that whereas individual gonadotropes exhibited two response states, inactive and active, both the probability of activation and the average response in activated cells increased with increasing GnRH concentration. These data indicate a hybrid single-cell response having both digital (switch-like) and analog (graded) features. Mathematical modeling suggests that the hybrid response can be explained by indirect thresholding of ERK activation resulting from the distributed structure of the GnRH-modulated network. The hybrid response mechanism improves the reliability of noisy reproductive signal transmission from the brain to the pituitary.

Received for publication, July 7, 2006 , and in revised form, August 17, 2006.

^* This research was supported by National Institutes of Health Grant DK46943. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S9 and Tables S1-S4.

¹ To whom correspondence should be addressed: Neurology Box 1137, One Gustave L. Levy Place, New York, NY 10029. Tel.: 212-241-7075; Fax: 212-289-4107; E-mail: stuart.sealfon{at}mssm.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Feng, M. A. Lawson, and P. Melamed A Proteomic Comparison of Immature and Mature Mouse Gonadotrophs Reveals Novel Differentially Expressed Nuclear Proteins that Regulate Gonadotropin Gene Transcription and RNA Splicing Biol Reprod, September 1, 2008; 79(3): 546 - 561. [Abstract] [Full Text] [PDF]

				U. B. Kaiser Genetic Labeling: New Approaches to Creating a Gonadotroph "ID" Endocrinology, June 1, 2008; 149(6): 2699 - 2700. [Full Text] [PDF]

				S. Wen, J. R. Schwarz, D. Niculescu, C. Dinu, C. K. Bauer, W. Hirdes, and U. Boehm Functional Characterization of Genetically Labeled Gonadotropes Endocrinology, June 1, 2008; 149(6): 2701 - 2711. [Abstract] [Full Text] [PDF]

				M. A. Lawson, R. Tsutsumi, H. Zhang, I. Talukdar, B. K. Butler, S. J. Santos, P. L. Mellon, and N. J. G. Webster Pulse Sensitivity of the Luteinizing Hormone {beta} Promoter Is Determined by a Negative Feedback Loop Involving Early Growth Response-1 and Ngfi-A Binding Protein 1 and 2 Mol. Endocrinol., May 1, 2007; 21(5): 1175 - 1191. [Abstract] [Full Text] [PDF]