title: Testosterone inhibition of growth hormone release stimulated by a growth hormone secretagogue: studies in the rat and dog.
abstract: Anabolic steroids are frequently taken by athletes and bodybuilders together with recombinant human GH (rhGH), though there is some scientific evidence that the use of anabolic steroids reverses the rhGH-induced effects. Recently, we have shown that treatment with rhGH (0.2 IU/kg s.c., daily x 12 days) in the dog markedly reduced the canine GH (cGH) responses stimulated by EP51216, a GH secretagogue (GHS), evaluated after 3 and 5 daily rhGH injections, and that the inhibition was still present a few days after rhGH discontinuation. The aim of the present study was to evaluate in the dog the GH response to EP51216 (125 mug/kg i.v.) in a condition of enhanced androgenic function (i.e. acute injection or 15-day treatment with testosterone at the dose of 2 mg/kg i.m. on alternate days), and in the hypophysectomized rat the hypothalamic and hippocampal expression of ghrelin, the receptor of GHSs (GHS-R), GH-releasing hormone (GHRH) and somatostatin (SS) after specific hormonal replacement therapies (testosterone, 1 mg/kg/day s.c.; hydrocortisone, 500 mug/kg/day s.c.; rhGH, 400 mug/kg/day s.c.; 0.9% saline 0.1 ml/kg/day s.c.; x11 days). In the dog experiments, under baseline conditions, a single injection of EP51216 elicited an abrupt rise of plasma cGH. Twenty-four hours from the acute bolus injection of testosterone, C(max) and AUC(0-90) of the GHS-stimulated cGH response were significantly lower than baseline cGH response; 5 days later, there was still a significant decrease of either parameter versus the original values. Short-term treatment with testosterone markedly reduced the GHS-stimulated cGH responses evaluated during (5th bolus) and at the end (8th bolus) of testosterone treatment. Four and 8 days after testosterone withdrawal, the EP51216-stimulated cGH response was still significantly reduced when compared with that under baseline conditions. Plasma concentrations of insulin-like growth factor 1 (IGF-1) were stable until the 5th bolus of testosterone and decreased progressively in the remaining time of the testosterone treatment; 4 and 8 days from treatment withdrawal, IGF-1 levels were still suppressed. In rat studies, hypothalamic mRNA levels of GHS-R were significantly reduced by treatments with testosterone and hydrocortisone, whereas hippocampal expressions of ghrelin, GHRH and SS were reduced by rhGH replacement therapy. In conclusion, these studies show that a single administration of testosterone can abrogate the cGH response ensuing acute stimulation by a GHS; the inhibitory effect of testosterone on the cGH response to GHS is present during and even 8 days after termination of a short-lived treatment with testosterone; these events occur via a
authors.affiliation: Department of Medical Pharmacology, University of Milan, Milan, Italy.
authors.forename: Antonello E
authors.initials: AE
authors.lastname: Rigamonti
authors.forename: Silvano G
authors.initials: SG
authors.lastname: Cella
authors.forename: Claudio
authors.initials: C
authors.lastname: Giordani
authors.forename: Sara M
authors.initials: SM
authors.lastname: Bonomo
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Giunta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sartorio
authors.forename: Eugenio
authors.initials: E
authors.lastname: Muller
mesh_terms: D045930:Anabolic Agents / Q000008:administration & dosage; D000818:Animals; D004285:Dogs; D054439:Ghrelin; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D019382:Human Growth Hormone / Q000008:administration & dosage; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D036361:Peptide Hormones / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism; D011994:Recombinant Proteins; D013004:Somatostatin / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage / Q000502:physiology*
chemical_list: D045930:Anabolic Agents; D054439:Ghrelin; D009842:Oligopeptides; D036361:Peptide Hormones; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; C420120:gamma-aminobutyryl-2-methyltryptophyl-2-methyltryptophyl-2-methyltryptophyl-lysinamide; D019382:Human Growth Hormone; D013739:Testosterone; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone