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Published-Ahead-of-Print August 23, 2006, DOI:10.2164/jandrol.106.000257
Journal of Andrology, Vol. 28, No. 1, January/February 2007
Copyright © American Society of Andrology
DOI: 10.2164/jandrol.106.000257

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Prolonged Histamine Deficiency in Histidine Decarboxylase Gene Knockout Mice Affects Leydig Cell Function

CAROLINA MONDILLO*, ANDRÁS FALUS{dagger}, OMAR PIGNATARO*,{ddagger} AND ERNA PAP{dagger}

From the * Lab of Molecular Endocrinology and Signal Transduction, Institute of Biology and Experimental Medicine-CONICET, Buenos Aires, Argentina; the {dagger} Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; and the {ddagger} Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.

Correspondence to: Carolina Mondillo, PhD, Laboratory of Molecular Endocrinology and Signal Transduction, Institute of Biology and Experimental Medicine (IByME-CONICET), Vuelta de Obligado 2490, CP 1428, Buenos Aires, Argentina (e-mail: mondillo{at}dna.uba.ar).

Reprint requests to: Erna Pap, PhD, Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, Budapest, Hungary (e-mail: nyierna{at}dgci.sote.hu).

The present study focuses on histaminergic regulation of Leydig cell physiology, since limited information is available so far. To evaluate the dependency of Leydig cells on histamine (HA), we performed experiments using highly purified Leydig cells in culture, isolated from wild type (WT) and histidine decarboxylase (Hdc) gene knockout (HDC KO)—so HA-deprived—mice. HDC KO Leydig cells showed lower basal and human choriogonadotropin (hCG)-induced testosterone production compared to WT Leydig cells, presumably due to altered P450scc gene (Cyp11a1) expression levels. Moreover, in HDC KO cells, hCG did not increase basal expression levels of HA H1 and H2 receptor genes, while the hormone showed a significant inducing effect in WT cells. Based on these findings, we propose that prolonged HA deficiency in HDC KO mice affects various aspects of Leydig cell physiology, most importantly the response to hCG, providing definite evidence that HA plays a role as direct modulator of Leydig cell function and steroid synthesis in the testis. Also, the results presented herein constitute the first molecular evidence for the expression of HA H1 and H2 receptor subtypes in isolated Leydig cells.

     Key words: Steroidogenesis, human choriogonadotropin




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C. Mondillo, R. M. Pagotto, B. Piotrkowski, C. G. Reche, Z. J. Patrignani, C. B. Cymeryng, and O. P. Pignataro
Involvement of Nitric Oxide Synthase in the Mechanism of Histamine-Induced Inhibition of Leydig Cell Steroidogenesis via Histamine Receptor Subtypes in Sprague-Dawley Rats
Biol Reprod, January 1, 2009; 80(1): 144 - 152.
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