Intratesticular regulation of testosterone secretion: comparison of the effects and interactions of hCG, an LHRH agonist and testicular interstitial fluid on Leydig cell testosterone secretion in vitro

Abstract

The stimulatory effects on Leydig cell testosterone secretion of a polypeptide(s) factor present in testicular interstitial fluid (IF) were compared with those of hCG and an LHRH agonist (LHRH-A). The actions of IF and LHRH-A were similar in showing (1) a delayed onset of action, (2) enhancement of testosterone production in response to a maximally stimulating concentration (5 nM) of hCG, and (3) near cessation of stimulation following their removal from the incubation medium. However, addition of an LHRH antagonist blocked only the actions of LHRH-A. Moreover, IF continued to stimulate testosterone production up to at least 20 h either on its own or in the presence of 5 nM hCG, whereas the stimulatory effects of LHRH-A disappeared beyond 6 h. IF was also able to enhance testosterone production in response to LHRH-A or in response to hCG + LHRH-A. IF enhanced testosterone production over 4–20 h in response to all doses of hCG and increasing concentrations of IF caused dose-dependent increments in the rate of hCG (5 nM) -stimulated testosterone production. With submaximally stimulating doses of hCG or with LHRH-A alone, the stimulatory effect of IF was more or less additive, whereas with maximally stimulating doses of hCG the effect of IF was clearly synergistic. Thus, whereas the rate of testosterone production by Leydig cells in response to 5 nM hCG declined progressively from 4 to 20 h, addition of IF attenuated or prevented this decline. These findings have implications with respect to the physiological control of intratesticular testosterone levels and with respect to the regulation of steroidogenesis. They also imply that isolation of Leydig cells from their normal stimulatory environment results in a decrease in their steroidogenic responsiveness.