J. S~eroid Biochem. Molec. Biol. Vol. 40, No. 1-3, pp. 165-173, 1991 0960-0760/91 $3.00 + 0.00 Printed in Great Britain. All rights reserved Copyright © 1991 PergamonPress plc THE ROLE OF SEXUAL STEROIDS IN THE MODULATION OF GROWTH HORMONE (GH) SECRETION IN HUMANS JESUS DEVESA,* NOEMI LOIS, VICTOR ARCE, MARIA J. DIAZ, LuIs LIMA and JESUS A. F. TRESGUERRES l Department of Physiology, Faculty of Medicine, Santiago de Compostela and ~Department of Physiology, Faculty of Medicine, Madrid, Spain Summary--Sex steroids contribute to modulate GH secretion in man. However, both the exact locus and mechanism by which their actions are exerted still remain not clearly understood. We undertook a number of studies designed to ascertain: (1) whether or not sudden or chronic changes in circulating gonadal steroids may affect GH secretion in normal adults; and (2) the reason(s) for gender-related dimorphic pattern of GH release. The pituitary reserve of GH, as evaluated by means of a GHRH challenge, was similar in women with anorexia nervosa and in normally menstruating women. Estrogenic receptor blockade with tamoxifen (TMX) did not significantly change GHRH-induced GH response in these normal women. Therefore, acute or chronic hypoestrogenism apparently had no important effects at level of somatotrophs. In another group of normal women we tested the possibility that changes in circulating estrogens might induce changes in the hypothalamic-somatotroph rhythm (HSR). GHRH challenges were performed throughout a menstrual cycle, and again after having achieved functional ovarian blockade with a GnRH agonist treatment. Short-term ovarian blockade did not significantly affect the parameters of GH response to GHRH, although it was ac- companied by an increase in the number of women in a refractory HSR phase at testing. This suggested a low potentiating effect on the basic pattern of somatostatin (SS) release occurring as a consequence of the decrease in circulating estrogens. In normal men, neither the GH response to GHRH nor the HSR were affected by functional testicular blockade (after GnRH agonist treatment). However, the administration of testoster- one enanthate (250 mg) to another group of men increased both the GHRH-induced GH release and the number of subjects in a spontaneous secretory HSR phase at testing; these were reversed by estrogenic receptor blockade with TMS. In another group of normal men, the fraction of GH secreted in pulses (FGHP) during a nocturnal sampling period was significantly decreased by testicular blockade. Other par- ameters of GH secretion, such as the number of GH pulses and their mean amplitude (A), and the mean plasma GH concentration (MCGH), showed a slight, although not significant, decrease following the lack of androgens. The administration of testosterone enanthate (500 mg) reversed these parameters to values similar to those in the basal study. Interestingly, when tamoxifen was given after testosterone enanthate, A, MCGH and FGHP increased to values significantly higher than in any other experimental condition in that study. In all, these data suggest that 17fl-estradiol may participate in GH modulation by inhibiting the hypothalamic release of somatostatin, while testosterone stimulates it. The results obtained after estrogenic receptor blockade appear to indicate that the effect of testosterone in such a modulation is dependent on its aromatization to 17fl-estradiol. The differential levels of this steroid in both sexes might account for the sexual dimorphic pattern of GH secretion. From other data in the literature, obtained in rats, and our preliminary data in children with constitutional delay of growth and puberty, it is tempting to speculate that the effect of 17fl-estradiol may be exerted by modifying the functional activity of a-2 adrenergic pathways involved in the negative modulation of SS release. INTRODUCTION Pituitary GH secretion occurs episodically in all species in which it has been examined [1]. This Proceedings of the Vlllth International Congress on Hormonal Steroids, The Hague, The Netherlands, 1(~21 September 1990. *To whom correspondence should be addressed. is mainly dependent on the rhythmic alternation in the hypothalamic release of two peptides: GHRH and somatostatin (SS) acting as stimu- latory and inhibitory hormones, respectively [2]. Each GH secretory episode would be initiated by a burst of GHRH release into the hypophy- seal portal system, preceded by a reduction of 165