[G1 spermatogonial chalone]

Abstract

Chalones are physiological inhibitors of cell proliferation that act either at the G1 or G2 phase of the cell cycle. They have been described for a variety of tissues, including the seminiferous epithelium. In vivo and in vitro characterization of rat G1 spermatogonial chalone demonstrate that it is a glycoprotein, heat-labile, molecular weight under 5,000 D, tissue specific but not species-specific, active at physiological pH, with a mechanism of cell action mediated by cyclic AMP. The origin of the substance are the differentiated cells of the spermatogenesis from primary spermatocytes up to round spermatids. The target cells are the type A (and perhaps only the A0) spermatogonia. The inhibitory effect, measured as a decrease in the uptake of H3-thymidine into testicular DNA, is not dependent on testicular steroids, Sertoli cell products (inhibin or the like) nor on the hypothalamic-hypophyseal-gonadal axis, since it occurs in vitro. In the mouse, the biological half-life (in vivo) of the G1 spermatogonial chalone is around 14 hs. Chronic administration for the entire length of mouse spermatogenesis does not alter spermatogenic kinetics nor does it result in azoospermia. The biological effect of the G1 spermatogonial chalone can be counteracted in vitro by means of an immune rabbit serum raised against a partially purified rat testicular extract (source of the chalone).