Endocrinology, Vol 133, 2445-2452, Copyright © 1993 by Endocrine Society

ARTICLES

Growth hormone binding protein in the rat: effects of gonadal steroids

DF Carmignac, BG Gabrielsson and IC Robinson
Division of Neurophysiology and Neuropharmacology, National Institute for Medical Research, Mill Hill, London, United Kingdom.

In normal rats, females have higher circulating GH-binding protein (GHBP) levels than males, whereas in the GH-deficient dwarf (Dw) rat, there is no sexual dimorphism in plasma GHBP, suggesting that GH secretion may be involved in this difference. In order to study the relationship between gonadal steroids and GH on GHBP and GH receptor regulation, the levels of plasma GHBP, hepatic bovine GH, and human GH (hGH) binding as well as GHBP and GH receptor messenger RNA (mRNA) have now been studied in normal, Dw, hypophysectomized (Hx), or ovariectomized (Ovx) rats, subjected to different GH and gonadal steroid exposure. In normal male rats, estradiol (E2, 12.5-25 micrograms/day for 1 or 2 weeks) markedly increased plasma GHBP and hepatic hGH, and bGH binding. These effects of E2 were diminished in Dw rats, absent in Hx rats, but restored in Hx rats given exogenous hGH. Plasma GHBP rose in female rats given E2, and fell in females given the anti-estrogen tamoxifen. Ovx animals had lower plasma GHBP and hepatic GH binding which was reversed by E2, but not testosterone treatment. Continuous hGH infusions in Ovx rats restored hepatic GH binding, and increased plasma GHBP. In Dw males, hGH increased plasma GHBP and hepatic GH binding, whereas testosterone had no effect on GHBP or GH receptors and did not affect their up-regulation by hGH. Hepatic levels of GHBP-, and GH receptor mRNA transcripts showed the same trends in response to steroid or GH treatment, but the differences were rarely significant, except in Ovx animals which had higher GHBP mRNA transcripts after GH or E2 treatment. Thus E2 and GH increase both plasma GHBP and hepatic GH receptor binding. GH up-regulates GHBP in the absence of E2, whereas E2 treatment does not raise GHBP in the absence of GH. Whereas some of the effects of estrogen could be mediated via alterations in GH secretion, estrogen may also directly influence GHBP production at the liver, but only in the presence of GH.

This article has been cited by other articles:

				K.-C. Leung, J. Brce, N. Doyle, H. J. Lee, G. M. Leong, K. Sjogren, and K. K. Y. Ho Regulation of Growth Hormone Signaling by Selective Estrogen Receptor Modulators Occurs through Suppression of Protein Tyrosine Phosphatases Endocrinology, May 1, 2007; 148(5): 2417 - 2423. [Abstract] [Full Text] [PDF]

				B. Jiao, X. Huang, C. B. Chan, L. Zhang, D. Wang, and C. H K Cheng The co-existence of two growth hormone receptors in teleost fish and their differential signal transduction, tissue distribution and hormonal regulation of expression in seabream J. Mol. Endocrinol., February 1, 2006; 36(1): 23 - 40. [Abstract] [Full Text] [PDF]

				K.-C. Leung, G. Johannsson, G. M. Leong, and K. K. Y. Ho Estrogen Regulation of Growth Hormone Action Endocr. Rev., October 1, 2004; 25(5): 693 - 721. [Abstract] [Full Text] [PDF]

				M. Bondanelli, A. Margutti, M. R. Ambrosio, L. Plaino, L. Cobellis, F. Petraglia, and E. C. degli Uberti Blood Growth Hormone-Binding Protein Levels in Premenopausal and Postmenopausal Women: Roles of Body Weight and Estrogen Levels J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1973 - 1980. [Abstract] [Full Text]

				J.-L. Liu, S. Yakar, and D. LeRoith Mice Deficient in Liver Production of Insulin-Like Growth Factor I Display Sexual Dimorphism in Growth Hormone-Stimulated Postnatal Growth Endocrinology, December 1, 2000; 141(12): 4436 - 4441. [Abstract] [Full Text] [PDF]

				M.F. Kritzer, A. Adler, J. Marotta, and T. Smirlis Regionally Selective Effects of Gonadectomy on Cortical Catecholamine Innervation in Adult Male Rats Are Most Disruptive to Afferents in Prefrontal Cortex Cereb Cortex, July 1, 1999; 9(5): 507 - 518. [Abstract] [Full Text] [PDF]

				A. G. Johansson, B. E. Engström, S. Ljunghall, F. A. Karlsson, and P. Burman Gender Differences in the Effects of Long Term Growth Hormone (GH) Treatment on Bone in Adults with GH Deficiency J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2002 - 2007. [Abstract] [Full Text]

				V. Chandrashekar, A. Bartke, K. T. Coschigano, and J. J. Kopchick Pituitary and Testicular Function in Growth Hormone Receptor Gene Knockout Mice Endocrinology, March 1, 1999; 140(3): 1082 - 1088. [Abstract] [Full Text]

				N. A. Pampori and B. H. Shapiro Gender Differences in the Responsiveness of the Sex-Dependent Isoforms of Hepatic P450 to the Feminine Plasma Growth Hormone Profile Endocrinology, March 1, 1999; 140(3): 1245 - 1254. [Abstract] [Full Text]

				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]

				D. F. Carmignac, P. A. Bennett, and I. C. A. F. Robinson Effects of Growth Hormone Secretagogues on Prolactin Release in Anesthetized Dwarf (dw/dw) Rats Endocrinology, August 1, 1998; 139(8): 3590 - 3596. [Abstract] [Full Text] [PDF]

				M. Tzanela, C. Wagner, and G. Shaffer Tannenbaum Recombinant Human Growth Hormone-Binding Protein Fails to Enhance the in Vivo Bioactivity of Human Growth Hormone in Normal Rats Endocrinology, December 1, 1997; 138(12): 5316 - 5324. [Abstract] [Full Text] [PDF]

				F. I. Sharara, D. Bhartiya, and L. K. Nieman Growth Hormone Receptor Gene Expression in the Mouse Uterus: Modulation by Gonadal Steroids Reproductive Sciences, October 1, 1994; 1(4): 285 - 289. [Abstract] [PDF]