TESTOSTERONE REGULATES GONADOTROPIN-RELEASING HORMONE-INDUCED CALCIUMSIGNALS IN MALE-RAT GONADOTROPHS

As the GnRH-induced secretion of gonadotropins is critically dependent upon an increase in the intracellular calcium ion concentration ([Ca2 +](i)) and modulated by gonadal factors, the effects of gonadal steroi ds on the pattern of calcium mobilization in single gonadotrophs of th e male rat were examined using the fluorescent Ca2+ indicator fura-2/A M. In cells from intact rats, low concentrations of GnRH induce repeti tive oscillations in [Ca2+](i), whereas spike-plateau responses are ob served at higher concentrations in single gonadotrophs. After castrati on, there was a significant change in the relationship between the GnR H concentration and the changes in [Ca2+](i). Increasing concentration s of GnRH (to 1 mu M) generate fewer spike-plateau responses in gonado trophs from castrate rats, with oscillatory responses predominating. T his change develops with time after castration, with the proportion of cells oscillating in response to 100 nM GnRH peaking by 7 days. This effect of castration on GnRH-induced [Ca2+](i) signals was reversed by treatment with testosterone propionate (100 mu g/100 g BW . day). Cas tration-induced decreases in serum testosterone, seminal vesicle, and prostate weights and increases in serum LH concentration were also cor rected by testosterone propionate treatment. These findings demonstrat e that testosterone regulates GnRH-stimulated Ca2+ signals in gonadotr ophs and suggest that gonadal steroids exert a regulatory role in the secretion of gonadotropinss at the level of Ca2+ mobilization.