title: Activation of the somatotropic axis by testosterone in adult men: evidence for a role of hypothalamic growth hormone-releasing hormone.
abstract: Testosterone (T) is known to affect the growth hormone (GH) axis. However, the mechanisms underlying the activation of GH secretion by T still remain to be clarified. Available data in animals and humans have shown that withdrawal of somatostatin (SRIH) infusion induces a GH-releasing hormone (GHRH)-mediated rebound release of GH, and there is accumulating evidence that SRIH infusion withdrawal may be a useful test to probe the GHRH function in vivo. With the aim of investigating whether the stimulatory effect of androgens on GH release in man could be accounted for by activation of the hypothalamic GHRH tone, we evaluated the plasma GH response to SRIH withdrawal in 10 patients aged 29.6 +/- 2.4 years (mean +/- SEM), diagnosed with hypergonadotropic hypogonadism, before and after a 6-month replacement therapy with T enanthate (250 mg every 3 weeks, i.m.), and in 10 healthy men, aged 26.7 +/- 2.8 years. To verify whether the modulation of GH secretion by T could also be mediated through changes in SRIH tone and/or pituitary releasable pool, we examined GH secretory responses to combined GHRH and L-arginine (ARG) in the same individuals. Basal plasma concentrations of GH (0.48 +/- 0.11 microg/l) and IGF-I (23.79 +/- 1.83 nmol/l) were significantly lower in untreated hypogonadal patients than in healthy men, and significantly increased after T replacement therapy (GH 1.13 +/- 0.28 microg/l; IGF-I 28.71 +/- 1.46 nmol/l). The mean Delta GH peak after SRIH withdrawal recorded in untreated hypogonadal men (2.65 +/- 0.86 microg/l) was significantly (p < 0.05) lower than that observed in healthy men (6.53 +/- 1.33 microg/l) and significantly increased after T replacement therapy (5.52 +/- 1.25 microg/l). The GH responses to GHRH combined with ARG (a functional SRIH antagonist) were not significantly different between healthy men and untreated hypogonadal patients, and were not significantly affected by T treatment. Plasma T and estradiol (E(2)) levels significantly correlated with Delta GH peak after SRIH withdrawal in healthy men and in T-treated hypogonadal patients, whereas in untreated patients they did not. No significant correlation was found between GH areas under the curve after GHRH + ARG test and T and E(2) plasma levels in either healthy men or in hypogonadal patients (both before and after T replacement). These findings are consistent with the view that in humans the stimulatory action of T on the GH axis appears to be mediated at the hypothalamic level primarily by promoting GHRH function.
authors.affiliation: Department of Biomedical Sciences and Advanced Therapies, Section of Endocrinology, University of Ferrara, Ferrara, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Bondanelli
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Ambrosio
authors.forename: Angelo
authors.initials: A
authors.lastname: Margutti
authors.forename: Paola
authors.initials: P
authors.lastname: Franceschetti
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Zatelli
authors.forename: Ettore C
authors.initials: EC
authors.lastname: degli Uberti
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001120:Arginine / Q000008:administration & dosage / Q000378:metabolism; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D013006:Growth Hormone / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000187:drug effects / Q000378:metabolism*; D006537:Heptanoates / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D015592:Immunoradiometric Assay; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D013004:Somatostatin / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage* / Q000378:metabolism*
chemical_list: D006537:Heptanoates; D013739:Testosterone; D004958:Estradiol; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine