title: 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.
authors.affiliation: Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, MD 20892-1276, USA. Peter.Schmidt@NIH.GOV
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schmidt
authors.forename: Jamuna
authors.initials: J
authors.lastname: Raju
authors.forename: Merry
authors.initials: M
authors.lastname: Danaceau
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Murphy
authors.forename: Robin E
authors.initials: RE
authors.lastname: Berlin
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000139:chemically induced*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D016729:Leuprolide / Q000009:adverse effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D012727:Sex Characteristics
chemical_list: D012739:Gonadal Steroid Hormones; D010879:Piperazines; D011374:Progesterone; D004958:Estradiol; D016729:Leuprolide; C015068:1-(3-chlorophenyl)piperazine