The Effects of Gender and Gonadal Steroids on the Neuroendocrine and Temperature Response to m-Chlorophenylpiperazine in Leuprolide-induced Hypogonadism in Women and Men

Abstract

Studies of the effects of gender and gonadal steroids on serotonergic activity in humans are few in number and often contradictory. We examined the neuroendocrine and core temperature response to a serotonergic stimulus, m-chlorophenylpiperazine (m-CPP) (0.08 mg/kg body weight, IV), in asymptomatic female and male volunteers during induced hypogonadism (leuprolide acetate) and hormone replacement (estradiol (E2) or progesterone (P4) in women; testosterone (T) in men).Compared with the hypogonadal state, basal prolactin (PRL) secretion was significantly higher during both P4 and E2 replacement (p < .05) in women and during T replacement in men (p < .05). m-CPP stimulated PRL secretion was significantly greater only during P4 (p < .05) but not E2 (women) or T (men) replacement, compared with hypogonadism. Basal but not stimulated plasma growth hormone (GH) levels were significantly higher during P4 in women and T in men (p < .05), and no significant differences in basal or m-CPP stimulated plasma levels of ACTH or cortisol were observed. Finally, basal core temperatures were significantly higher during P4 replacement compared with either E2 replacement or the hypogonadal condition (p < .01) in women, with no differences observed in men. Comparisons of measures by gender (and matched for baseline plasma T levels) revealed that during the hypogonadal state m-CPP–stimulated GH secretion was significantly greater (p < .01) and m-CPP–stimulated ACTH (p < .05) and cortisol (p < .01) significantly less in women compared with men.Although our data are limited to those components of the central serotonergic system influenced by m-CPP administration, our findings suggest the following: the regulatory effects of gonadal steroids on serotonergic function are modest in humans during leuprolide-induced hypogonadism; menstrual cycle phase effects of serotonergic agents on PRL secretion may reflect both the effects of P4 and E2; the effects of P4 in humans may occur without E2 priming of the progesterone receptor; and gender differences in GH secretion occur independent of the presence of gonadal steroids.