Divergent effects of short term glucocorticoid excess on the gonadotropic and somatotropic axes in normal men.
We investigated the effects of short term glucocorticoid excess on the gonadotropic and somatotropic axes in healthy men. Subjects (n = 5) underwent blood sampling at 10-min intervals for 6 h before and on days 2, 5, and 8 of glucocorticoid treatment, and for 24 h (n = 6) to examine pulsatile LH and GH release before and during dexamethasone administration (1.5 mg orally twice daily for 1 week). In the time-course study, we found significant decreases on day 8 in serum concentrations of estradiol (from 144 +/- 18 to 99 +/- 18 pmol/L), free testosterone (from 105 +/- 10 to 87 +/- 10 pmol/L), and dehydroepiandrosterone sulfate (from 6.0 +/- 1.6 to 1.7 +/- 0.3 mumol/L; P less than 0.05). Mean serum LH concentrations did not change (baseline, 5.3 +/- 1.2 IU/L; glucocorticoid, 4.2 +/- 0.61 IU/L). The mean plasma somatomedin-C concentration rose from 0.74 +/- 0.08 to 2.0 +/- 0.35 U/mL (P less than 0.05), and the mean serum GH concentration increased from 1.2 +/- 0.90 micrograms/L (basal) to 4.2 +/- 1.5 micrograms/L (day 8 of dexamethasone; P less than 0.01). Deconvolution analysis of 24-h serum GH and LH concentration profiles revealed that the half-life of endogenous GH and the duration and amplitude (maximal rate of secretion) of computer-resolved GH secretory bursts were not influenced significantly by dexamethasone. The mass of GH secreted per burst rose 1.6-fold. Glucocorticoid treatment also increased detectable GH secretory burst frequency from 12 +/- 1.6 to 18 +/- 1.6 episodes/24 h, decreased the GH interburst interval from 127 +/- 23 to 79 +/- 5 min, and increased the daily GH secretion rate from 41 +/- 11 to 101 +/- 11 micrograms/L.day. These effects on the somatotropic axis were specific, since the half-life of LH; LH secretory burst frequency, amplitude, mass, and duration; and the total daily LH production rate (and LH secretion in response to exogenous GnRH) were not altered by dexamethasone administration. We conclude that short term moderate glucocorticoid excess augments pulsatile GH secretion without influencing the episodic release of LH in normal men.
Veldhuis
J D
JD
Department of Internal Medicine, National Science Foundation Science Center in Biological Timing, University of Virginia Health Sciences Center, Charlottesville 22908.
Lizarralde
G
G
Iranmanesh
A
A
D000328:Adult; D003907:Dexamethasone / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D009994:Osmolar Concentration; D011673:Pulsatile Flow; D012016:Reference Values; D013997:Time Factors
D003907:Dexamethasone; D007986:Luteinizing Hormone; D013006:Growth Hormone