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  • 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.
    Author: Schmidt PJ, Raju J, Danaceau M, Murphy DL, Berlin RE.
    Journal: Neuropsychopharmacology; 2002 Nov; 27(5):800-12. PubMed ID: 12431854.
    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.
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