Direct inhibition of testicular androgen biosynthesis revealing antigonadal activity of neurohypophysial hormones

Abstract

Vertebrate neurohypophysial hormones are known to have antidiuretic, vasopressor and oxytocic properties^1,2. However, arginine-vasotocin (AVT), the most primitive of the neurohypophysial principles and one that has been reported to occur in the mammalian pineal gland^3–7, also retards murine pubertal progression^8–10 and canine testicular steroidogenesis^11,12. Although AVT may exert its inhibitory effect in vivo by reducing the release of pituitary gonadotropins^13,14, the possibility of a direct antigonadal action cannot be ruled out. Using a recently established primary culture system of rat testicular cells¹⁵, we now report that AVT as well as other naturally occurring neurohypophysial hormones can act independently of the hypothalamic–pituitary unit to exert a direct inhibition of testicular androgen biosynthesis in vitro. The observation that this inhibitory activity can be blocked by vasopressor-selective, but not oxytocic-selective antagonists, suggests that the antigonadal action of the neurohypophysial hormones is probably mediated by highly stereospecific testicular receptor sites. These findings constitute the first demonstration of a direct antigonadal activity of neurohypophysial hormones and may account, in part, for the previously recognized antireproductive activity of AVT. Future design of synthetic analogues of neurohypophysial hormones may lead to the development of new male contraceptive peptides capable of directly inhibiting Leydig cell androgen biosynthesis.