Histamine: a new autocrine/paracrine factor in the development of adult Leydig cells?

PAGOTTO RM; MONZÓN CM; PONZIO R; MONDILLO C; PIGNATARO OP

Campinhas

Congreso; III Workshop on Male Reproductive Biology; 2011

Universidad de Campinhas-Instituto de Biología

Histamine: a new autocrine/paracrine factor in the development of Adult Leydig Cells?   R.M. Pagotto1*, C.M. Monzón1, R. Ponzio3, C. Mondillo1, O.P. Pignataro12   1Institute of Experimental Medicine and Biology -National Council of Scientific and Technological Research, Buenos Aires, Argentina 2Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina 3 IdIR, School of Medicine, University of Buenos Aires, Argentina   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 Inmature Leydig Cells (ILC), before becoming ALC. These developmental stages involve proliferation and differentiation processes that are tightly 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 interactions between mast cells (HA-producing cells) and CL in the rat testis interstitium, and changes in the levels of testicular HA among different ages 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 accordance with the HDC levels found, which are highest at 7 days and decreases 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: 392.4±12.4; 10µM 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 transition of undifferentiated LC to Leydig Progenitors.