QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 31 January 2006
doi: 10.1242/jcs.02775

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.02775v1 119/4/733    most recent Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Estrada, M. Articles by Ehrlich, B. E. Search for Related Content PubMed PubMed Citation Articles by Estrada, M. Articles by Ehrlich, B. E. Social Bookmarking                         What's this?

Ca²⁺ oscillations induced by testosterone enhance neurite outgrowth

¹ Departments of Pharmacology, Cell and Molecular Physiology, Yale University, New Haven, CT 06520, USA
² Neurosciences Institute of the Marine Biological Laboratory, Woods Hole, MA 02543, USA

^* Author for correspondence (e-mail: barbara.ehrlich{at}yale.edu)

Accepted 1 November 2005

Testosterone has short- and long-term roles in regulating neuronal function. Here, we show rapid intracellular androgen receptor-independent effects of testosterone on intracellular Ca²⁺ in neuroblastoma cells. We identified testosterone-induced Ca²⁺ signals that began primarily at the neurite tip, followed by propagation towards the nucleus, which was then repeated to create an oscillatory pattern. The initial transient depended upon production of inositol 1,4,5-trisphosphate [Ins(1,4,5)P₃], but subsequent transients required both extracellular Ca²⁺ influx and Ca²⁺ release from intracellular stores. Inhibition of pertussis toxin-sensitive G-protein receptors or the use of siRNA for the Ins(1,4,5)P₃ receptor type 1 blocked the Ca²⁺ response, whereas inhibition or knock-down of the intracellular androgen receptor was without effect. Cytosolic and nuclear Ca²⁺ were buffered with parvalbumin engineered to be targeted to the cytosol or nucleus. Cytoplasmic parvalbumin blocked Ca²⁺ signaling in both compartments; nuclear parvalbumin blocked only nuclear signals. Expression of a mutant parvalbumin did not modify the testosterone-induced Ca²⁺ signal. Neurite outgrowth in neuroblastoma cells was enhanced by the addition of testosterone. This effect was inhibited when cytosolic Ca²⁺ was buffered and was attenuated when parvalbumin was targeted to the nucleus. Our results are consistent with a fast effect of testosterone, involving Ins(1,4,5)P₃-mediated Ca²⁺ oscillations and support the notion that there is synergism in the pathways used for neuronal cell differentiation involving rapid non-genomic effects and the classical genomic actions of androgens.

Key words: Androgens, Ca²⁺ signaling, Inositol, 1,4,5-trisphosphate receptor, Nongenomic response, Neurite outgrowth

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

This article has been cited by other articles:

				F. Altamirano, C. Oyarce, P. Silva, M. Toyos, C. Wilson, S. Lavandero, P. Uhlen, and M. Estrada Testosterone induces cardiomyocyte hypertrophy through mammalian target of rapamycin complex 1 pathway J. Endocrinol., August 1, 2009; 202(2): 299 - 307. [Abstract] [Full Text] [PDF]

				W. Boehmerle, K. Zhang, M. Sivula, F. M. Heidrich, Y. Lee, S.-E. Jordt, and B. E. Ehrlich Chronic exposure to paclitaxel diminishes phosphoinositide signaling by calpain-mediated neuronal calcium sensor-1 degradation PNAS, June 26, 2007; 104(26): 11103 - 11108. [Abstract] [Full Text] [PDF]

				W. Boehmerle, U. Splittgerber, M. B. Lazarus, K. M. McKenzie, D. G. Johnston, D. J. Austin, and B. E. Ehrlich Paclitaxel induces calcium oscillations via an inositol 1,4,5-trisphosphate receptor and neuronal calcium sensor 1-dependent mechanism PNAS, November 28, 2006; 103(48): 18356 - 18361. [Abstract] [Full Text] [PDF]