Novel role for histamine through classical h1 and h2 receptors: regulation of leydig cell steroidogenesis and its implications for male reproductive function

Abstract

Most of the physiological functions of HA described to date have been linked to the well-characterized H1 and H2 receptors. Nevertheless, extensive research is continuously going on to elucidate new roles for these receptors. In this respect, 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. Interestingly, HA plays a role as autocrine/paracrine modulator of Leydig cell steroidogenesis in several experimental models, both in vivo and in vitro. It was demonstrated very recently that this modulatory effect is concentration-dependent and biphasic: while H1 receptor activation would be responsible for HA-mediated negative modulation of steroidogenesis, H2 receptor activation would lead to stimulation of steroid synthesis. 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. 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 functions which certainly deserves further investigation. C.