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Dual Role of Histamine in Modulation of Leydig Cell Steroidogenesis via HRH1 and HRH2 Receptor Subtypes¹

Lab of Molecular Endocrinology and Signal Transduction,³ Institute of Biology and Experimental Medicine-CONICET, CP 1428, Buenos Aires, Argentina Lab of Radioisotopes-School of Biochemistry,⁴ University of Buenos Aires, CP1113, Buenos Aires, Argentina Department of Biological Chemistry,⁵ School of Sciences, University of Buenos Aires, CP 1428, Buenos Aires, Argentina

Although several reports indicate effects of histamine (HA) on female reproductive functions, scant literature exists to suggest a physiological role of HA in the male gonad. In the present study, we report a dual concentration-dependent effect of HA on steroidogenesis in MA-10 murine Leydig cells and purified rat Leydig cells. Although 1 nM HA can stimulate steroid production and significantly increase the response to LH/hCG in these cells, 10 µM HA exerts an inhibitory effect. We also provide confirming evidence for the existence of functional HRH1 and HRH2 receptors in both experimental models. The use of HRH1 and HRH2 selective agonists and antagonists led us to suggest that HRH2 activation would be largely responsible for stimulation of steroidogenesis, while HRH1 activation is required for inhibition of steroid synthesis. Our results regarding signal transduction pathways associated with these receptors indicate the coupling of HRH2 to the adenylate cyclase system through direct interaction with a Gs protein. Moreover, we show HRH1 activation mediates increases in inositol phosphate production, possibly due to coupling of this receptor to Gq protein and phospholipase C activation. The data compiled in this report clearly indicate that HA can modulate Leydig cell steroidogenesis in the testis and suggest a possible new physiological site of action for HA. Given that many drugs binding to HRH1, HRH2, or both, are widely prescribed for the treatment of diverse HA-related pathologies, it seems necessary to increase the knowledge regarding histaminergic regulation of testicular functions, to avoid possible unexpected side effects of such substances in the testis.

cyclic adenosine monophosphate, Leydig cells, signal transduction, testis, testosterone

² Correspondence: Omar Pignataro, Instituto de Biología y Medicina Experimental, IBYME-CONICET, Vuelta de Obligado 2490, CP 1428, Buenos Aires, Argentina. FAX: 54 011 4786 2564; pignatar{at}dna.uba.ar

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				U. W Khan and U. Rai Differential effects of histamine on Leydig cell and testicular macrophage activities in wall lizards: precise role of H1/H2 receptor subtypes J. Endocrinol., August 1, 2007; 194(2): 441 - 448. [Abstract] [Full Text] [PDF]

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