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.
The increase in pituitary GH secretion that occurs during mid-late puberty in boys follows an increase in circulating testosterone (T) concentration; the direct mechanism by which this occurs is unknown. We hypothesized that T increases GH secretion during puberty by augmenting hypothalamic output of GHRH. Using constant infusions of a GHRH antagonist, we tested this hypothesis in six early pubertal boys with constitutional delay of growth and adolescence who had a mean chronological age of 14.0 +/- 0.3 yr and mean bone age of 11.4 +/- 0.2 yr. Blood samples were obtained from subjects every 15 min for 24 h during the overnight infusion of normal saline (2000-0600 h) and again during the overnight infusion of GHRH antagonist (0.33 microg/kg/h) the following night. Subjects then received transdermal T (5-mg patch) for 12 h nightly and were studied again after 4 wk of treatment. Serum samples were assayed for GH and total ghrelin; the percent suppression of GH during GHRH antagonist infusion was calculated. Morning serum T rose from 0.44 +/- 0.09 to 4.43 +/- 0.74 microg/liter (P = 0.005). T treatment was associated with a 92.6% increase in mean nocturnal GH secretion area under the curve (830 +/- 177 to 1599 +/- 340 microg/24 h.liter). Infusion of GHRH-antagonist suppressed mean nocturnal GH area under the curve by 29.1% before T treatment (830 +/- 177 to 621 +/- 168 microg/24 h.liter), and by 29.4% after T treatment (1599 +/- 340 to 1182 +/- 249 microg/24 h.liter; P = 0.99). Somatotroph sensitivity to GHRH was tested with 0.1- and 1.0-microg/kg doses of GHRH-44 iv; GH response did not change with regard to T treatment. The mean 24-h concentration of total ghrelin was unchanged with regard to T treatment. In summary, nightly transdermal T administration in six boys with constitutional delay of growth and adolescence increased GH output almost 2-fold, whereas the degree of GH suppressibility by GHRH antagonist remained unchanged. We conclude that the T-associated augmentation of GH secretion during early puberty in boys is unlikely to involve an absolute increase in hypothalamic GHRH output.
Racine
Michael S
MS
Division of Endocrinology and Metabolism, 3920 Taubman Center, Box 0354, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Symons
Kathy V
KV
Foster
Carol M
CM
Barkan
Ariel L
AL
D000293:Adolescent; D002940:Circadian Rhythm; D054439:Ghrelin; D006130:Growth Disorders / Q000188:drug therapy* / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D036361:Peptide Hormones / Q000097:blood; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011628:Puberty, Delayed / Q000188:drug therapy* / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000627:therapeutic use*
D054439:Ghrelin; D036361:Peptide Hormones; D019382:Human Growth Hormone; D013739:Testosterone; D013007:Growth Hormone-Releasing Hormone