Histamine in the testicle: new functions through classical H1 and H2 receptors

Histamine (HA) is undoubtfully one of the most important biogenic amines in medicine and biology. It is an extremely versatile molecule with a wide range of physiological functions. Recent reports have indicated expression of H1 and H2 receptors in germinal and peritubular cells of the testis, as well as in macrophages and Leydig cells. In addition, it was demonstrated very recently that HA plays a rote as autocrine/paracrine modulator of Leydig cell steroidogenesis in several experimental models, both in vivo and in vitro. So far, very little is known regarding expression of functional H3 and H4 receptors in Leydig cells, or in other cell types of the testis. Because antihistamine drugs target HA receptors, the novel role of HA as modulator of testicular steroidogenesis will surely attract more attention to possible unexpected side-effects of such drugs, which might alter the local balance and in turn enhance or decrease androgen production. In this regard, the more we know about HA receptors and their multiple functions, the more opportunity there will be for rational drug design. Considering that HA has been implicated in spermatogenesis, penile erection and sexual behavior as well as steroidogenesis, it appears that the amine plays an integral role in the regulation of male reproductive function which certainly deserves further investigation. Of note, several reports have linked testicular mast cells with the pathogenesis of testicular disorders. Bearing this in mind, a potential role of HA in testicular pathology associated with infertility should also be evaluated. (C) 2011 Asociacion Espanola de Andrologia, Medicina Sexual y Reproductiva. Published by Elsevier Espana, S.L. All rights reserved.