The long-term objective of this research is to elucidate the physiological role of four tachykinin peptides in the regulation of testicular function. Based on some preliminary results, our working hypothesis is that tachykinins are synthesized by the Leydig cells, and by acting directly on the same cells, they are able to modulate the release of steroids, mainly testosterone. Also, we believe that Sertoli cells may be able to synthesize tachykinins, and they are able to affect the function of the same cells. By modifying the secretory activity of Sertoli cells, tachykinins can influence the spermatogenic process and also affect Leydig cell function, since the existence of some Sertoli cell factors that modify Leydig cell function has been reported. In this investigation we propose to prove our hypothesis that tachykinins can affect testosterone secretion by Leydig cells in vitro, that neuropeptide gamma may be the most active tachykinin in this respect, and that they can also affect the secretory activity of lactic acid and estradiol production by cultures of Sertoli cells in vitro. We also propose to prove that tachykinins are produced both by the Leydig and Sertoli cells, by demonstrating beta- preprotachykinin gene expression in these cells, since beta- preprotachykinin is the precursor molecule for 3 tachykinins. We also plan to prove that tachykinins in the testes are under gonadotropic control, by demonstrating that gonadotropins can increase the concentration of these peptides in the testes. These studies will be carried out in the Siberian hamster (Phodopus sungorus). This rodent is very sensitive to environmental lighting changes, and undergoes gonadal involution when exposed to short photoperiod. This will allow us to study the effect of gonadotropic suppression of tachykinins in the testes. Furthermore, this species has high levels of tachykinins in several tissues, probably the testes among them. This may suggest a particular physiological importance of tachykinins in this species. These studies will produce data likely to give a more in-depth understanding of the mechanisms of control of male reproduction and this may have long-term implications, even for studies on human reproduction and reproductive health.
