Histamine: a new autocrine/paracrine factor in the development of Adult Leydig Cells?

ROMINA MARÍA PAGOTTO; CASANDRA MARGARITA MONZÓN; ROBERTO PONZIO; CAROLINA MONDILLO; OMAR PEDRO PIGNATARO

Workshop; III Workshop on Male Reproductive Biology; 2011

Adult Leydig cells (ALC) define the final population of Leydig cells in the adult testis. They develop from undifferentiated cells and go through intermediate stages, known as Leydig Progenitors and Immature Leydig cells (ILC), before becoming ALC. These developmental stages involve proliferation and differentiation processes that are tighlty regulated by factors present in the testicular environment. Histamine is a biogenic amine associated with heterogeneous functions. Recent studies focused on HA ability to modulate proliferation/differentiation in many different cell types. Evidence of interaction between mast cells (HA-producing cells) and CL in the rat testis interstitium, and changes in the levels of testicular HA among different stages in the male rat have led us to hypothesize that HA could be involved in the development of ALC, modulating proliferation processes. Herein, we compared HA testicular levels of Sprague Dawley rats at different LC developmental stages (7, 21, 35, 90 days) by IHC methods and testicular content of HA-synthesizing enzyme (HDC), by immunoblot assay. We also studied a direct effect of HA and its specific agonists on the proliferation of LC, using purified ILC in 3H-Thymidine incorporation assays. Results: testicular HA content is higher at early stages, in acordance with the HDC levels found, which are highest at 7 days and decrease with age (in DO, 7 days: 1.7 +/- 0,2; 90 days: 0.47 +/- 0.07). Although HA did not modify proliferation in ILC, the agonist HRH4 reduced it significantly (in cpm /well, control: 392 +/- 12.4; 10uM HRH4: 320.0 +/- 7.7). Conclusions: the inhibitory effect of HRH4 agonist on ILC proliferation suggests that HA may contribute in the development of ALC by modulating proliferation through HRH4 receptor. The higher testicular level of HA found at early LC developmental stages deserves further study about the role of this amine in the transtition of undifferentiated LC to Leydig progenitors. Finantial Support: PIP 382 (CONICET) and Grant 20020090100060 (FCEN-UBA) to OPP.