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ToxSci Advance Access published online on February 8, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm015
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Effect of Manganese on Luteinizing Hormone Releasing Hormone (LHRH) Secretion in Adult Male Rats

Juan Pablo Prestifilippo*, Javier Fernández-Solari*, Claudia Mohn*, Andrea De Laurentiis*, Samuel M. McCann*, W Les Dees{dagger} and Valeria Rettori*

* Centro de Estudios Farmacológicos y Botánicos, Facultad de Medicina (CEFyBO-CONICET-UBA); Universidad 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 December 5, 2006; revision received January 11, 2007; accepted February 5, 2007


  Abstract

Recently studies have demonstrated that low doses of (Mn+2) in the form of manganese chloride, can stimulate specific puberty-related hormones and advance signs of pubertal development in immature female and male rats. In the present study we used an in vitro system to evaluate the ability of 0, 50, 250 and 500uM doses of Mn+2 to stimulate luteinizing hormone releasing hormone (LHRH) secretion, and to assess the hypothalamic mechanism of this action in adult male Sprague-Dawley rats. We demonstrated that Mn+2 at 500uM, but not the lower doses, increased LHRH release, nitric oxide (NO) synthase (NOS) activity, and the content of cyclic cGMP in the medial basal hypothalamus (MBH). Inhibition of NOS with a competitive inhibitor (L-NAME) prevented the Mn-induced increase in LHRH release. Additionally, methilene blue (MB) and KT5823, specific inhibitors of guanylyl cyclase (GC) and protein kinase G (PKG) respectively, also blocked the stimulatory effect of Mn+2 on LHRH release. These in vitro studies demonstrated that the hypothalamic mechanism of Mn+2 action in adult males is by activation of the NOS/NO system, resulting in increases in cGMP and PKG, and thus, the secretion of LHRH from the nerve terminals. These results indicate Mn+2 can cause LHRH release in adult males, and this action is discussed in relation to age, gender, as well as mechanistic and functional differences between adult and immature animals.

Key Words: Nitric oxide; cGMP; protein kinase G; Medial Basal Hypothalamus.


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J. P. Prestifilippo, J. Fernandez-Solari, A. De Laurentiis, C. E. Mohn, C. de la Cal, R. Reynoso, W. L. Dees, and V. Rettori
Acute Effect of Manganese on Hypothalamic Luteinizing Hormone Releasing Hormone Secretion in Adult Male Rats: Involvement of Specific Neurotransmitter Systems
Toxicol. Sci., October 1, 2008; 105(2): 295 - 302.
[Abstract] [Full Text] [PDF]


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