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ToxSci Advance Access published online on July 4, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn135
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Acute effect of manganese on hypothalamic luteinizing hormone releasing hormone (LHRH) secretion in adult male rats: Involvement of specific neurotransmitter systems

Juan Pablo Prestifilippo*, Javier Fernández-Solari*, Andrea De Laurentiis*, Claudia Ester Mohn*, Carolina de la Cal*, Roxana Reynoso**, W. Les Dees{dagger} and Valeria Rettori*

* Center of Pharmacological and Botanical Studies (CEFyBO-CONICET-UBA) ** Department of Physiology, Medical School of University de Buenos Aires, Argentina {dagger} Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, USA

Corresponding author: Juan Pablo Prestifilippo, CEFYBO-CONICET-UBA, Facultad de Medicina, UBA, Paraguay 2155, piso 16, Buenos Aires, Argentina (1121), telephone: 54-11-4508-3680 extension 112, fax: 54-11-4508-3680 extension 106, jprestifilippo{at}yahoo.com.ar

Received April 23, 2008; revision received June 23, 2008; accepted June 24, 2008


  Abstract

Manganese chloride (MnCl2) is capable of stimulating luteinizing hormone releasing hormone (LHRH) secretion in adult male Sprague-Dawley rats through the activation of the hypothalamic nitric oxide/cGMP/protein kinase G pathway. The present study aimed to determine the involvement of specific neurotransmitters involved in this action. Our results indicate that dopamine (DA), but not glutamic acid and prostaglandinds, mediates the MnCl2 stimulated secretion of LHRH from medial basal hypothalami in vitro, as well as increases the activity of nitric oxide synthase. Furthermore, a biphasic response was observed in that gamma aminobutyric acid (GABA) release was also increased, which acts to attenuate the MnCl2 action to stimulate LHRH secretion. While it is clear that manganese (Mn+2) can acutely induce LHRH secretion in adult males, we suggest that the additional action of MnCl2 to release GABA, a LHRH inhibitor, may ultimately contribute to suppressed reproductive function observed in adult animals following exposure to high levels of Mn+2.

Key Words: Luteinizing Hormone; Prolactin; Dopamine; Gamma Aminobutyric Acid; Glutamic Acid; Prostaglandin E; Nitric Oxide.


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