Endocrinology, Vol 127, 1362-1368, Copyright © 1990 by Endocrine Society

ARTICLES

Growth hormone-releasing hormone messenger ribonucleic acid in the hypothalamus of the adult male rat is increased by testosterone

P Zeitler, J Argente, JA Chowen-Breed, DK Clifton and RA Steiner
Department of Obstetrics and Gynecology, University of Washington, Seattle 98195.

Since intact adult male rats have higher GH pulse amplitude than do castrated animals and since GH-releasing hormone (GHRH) secretion is predominantly responsible for the production of these GH pulses, we hypothesized that testosterone stimulates GHRH synthesis in neurons of the hypothalamus. To test this hypothesis, we compared GHRH mRNA content in individual neurons of the arcuate (ARC) and ventromedial (VMH) nuclei among groups of intact (n = 3), castrated (n = 5), and castrated testosterone-replaced (n = 5) adult male rats. Cellular GHRH mRNA content was measured by using semiquantitative in situ hybridization with an 35S-labeled cRNA probe complementary to the coding sequence of rat GHRH mRNA. Castration resulted in an approximately 35% decline in GHRH mRNA signal relative to that in intact animals in both the ARC (P less than 0.005) and VMH (P less than 0.005). Replacement with testosterone at the time of castration completely prevented the decline in both areas. Testosterone can exert effects either through activation of the androgen receptor directly or through aromatization to estradiol; therefore, we also examined the effects on GHRH mRNA of replacement with 17 beta-estradiol (n = 5) or dihydrotestosterone (DHT), a nonaromatizable androgen (n = 4). Estradiol had no effect on the castration-induced decline in GHRH mRNA in either the ARC or VMH. In contrast, DHT partially prevented the postcastration decline in GHRH in the ARC (P less than 0.005), while having no statistically significant effect on GHRH mRNA in the VMH. These results clearly indicate that testosterone stimulates expression of GHRH mRNA in neurons of the hypothalamus. Furthermore, the failure of estradiol to substitute for testosterone and the ability of DHT to substantially support GHRH mRNA suggest that testosterone exerts its effects on GHRH gene expression predominantly through direct activation of the androgen receptor.

This article has been cited by other articles:

				K. Bouyer, C. Loudes, I. C. A. F. Robinson, J. Epelbaum, and A. Faivre-Bauman Sexually Dimorphic Distribution of sst2A Somatostatin Receptors on Growth Hormone-Releasing Hormone Neurons in Mice Endocrinology, June 1, 2006; 147(6): 2670 - 2674. [Abstract] [Full Text] [PDF]

				H. Zhou, Y. Jiang, W. K W Ko, W. Li, and A. O L Wong Paracrine regulation of growth hormone gene expression by gonadotrophin release in grass carp pituitary cells: functional implications, molecular mechanisms and signal transduction J. Mol. Endocrinol., April 1, 2005; 34(2): 415 - 432. [Abstract] [Full Text] [PDF]

				H. Zhou, X. Wang, W. K. W. Ko, and A. O. L. Wong Evidence for a Novel Intrapituitary Autocrine/Paracrine Feedback Loop Regulating Growth Hormone Synthesis and Secretion in Grass Carp Pituitary Cells by Functional Interactions between Gonadotrophs and Somatotrophs Endocrinology, December 1, 2004; 145(12): 5548 - 5559. [Abstract] [Full Text] [PDF]

				J. J. Orrego, E. Dimaraki, K. Symons, and A. L. Barkan Physiological Testosterone Replenishment in Healthy Elderly Men Does Not Normalize Pituitary Growth Hormone Output: Evidence against the Connection between Senile Hypogonadism and Somatopause J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3255 - 3260. [Abstract] [Full Text] [PDF]

				M. S. Racine, K. V. Symons, C. M. Foster, and A. L. Barkan Augmentation of Growth Hormone Secretion after Testosterone Treatment in Boys with Constitutional Delay of Growth and Adolescence: Evidence against an Increase in Hypothalamic Secretion of Growth Hormone-Releasing Hormone J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3326 - 3331. [Abstract] [Full Text] [PDF]

				J. J. Orrego, M. Russell-Aulet, R. Demott-Friberg, and A. L. Barkan Semiquantification of Hypothalamic GH-Releasing Hormone Output in Women: Evidence for Sexual Dimorphism in the Mechanism of the Somatopause J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5485 - 5490. [Abstract] [Full Text] [PDF]

				J.-C. Painson, J. D. Veldhuis, and G. S. Tannenbaum Single exposure to testosterone in adulthood rapidly induces regularity in the growth hormone release process Am J Physiol Endocrinol Metab, May 1, 2000; 278(5): E933 - E940. [Abstract] [Full Text] [PDF]

				E. E. Muller, V. Locatelli, and D. Cocchi Neuroendocrine Control of Growth Hormone Secretion Physiol Rev, April 1, 1999; 79(2): 511 - 607. [Abstract] [Full Text] [PDF]

				A. Giustina and J. D. Veldhuis Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human Endocr. Rev., December 1, 1998; 19(6): 717 - 797. [Abstract] [Full Text]

				M. E. Wilson Regulation of the Growth Hormone-Insulin-Like Growth Factor I Axis in Developing and Adult Monkeys Is Affected by Estradiol Replacement and Supplementation with Insulin-Like Growth Factor I J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 2018 - 2028. [Abstract] [Full Text]

				E. Gevers, S. M. Pincus, I. C. A. F. Robinson, and J. D. Veldhuis Differential orderliness of the GH release process in castrate male and female rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 1998; 274(2): R437 - R444. [Abstract] [Full Text] [PDF]

				A. Giustina, T. Scalvini, C. Tassi, P. Desenzani, C. Poiesi, W. B. Wehrenberg, A. D. Rogol, and J. D. Veldhuis Maturation of the Regulation of Growth Hormone Secretion in Young Males with Hypogonadotropic Hypogonadism Pharmacologically Exposed to Progressive Increments in Serum Testosterone J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1210 - 1219. [Abstract] [Full Text] [PDF]