Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone (GH)-releasing hormone-stimulated GH secretion in healthy men: impact of gonadal steroid and GH secretory changes on metabolic outcomes.

J Clin Endocrinol Metab. 1997 Nov;82(11):3710-9.

Short-term modulation of the androgen milieu alters pulsatile, but not exercise-
or growth hormone (GH)-releasing hormone-stimulated GH secretion in healthy men:
impact of gonadal steroid and GH secretory changes on metabolic outcomes.

Fryburg DA, Weltman A, Jahn LA, Weltman JY, Samojlik E, Hintz RL, Veldhuis JD.

Department of Internal Medicine, General Clinical Research Center,
Charlottesville, Virginia, USA. david_a_fryburg@groton.pfizer.com

Gonadal steroids are known to alter GH secretion as well as tissue metabolism.
The present study was designed to examine the effects of short term (2- to
3-week) alterations in gonadal steroids on basal pulsatile (nonstimulated) and
exercise- and GH-releasing hormone-stimulated GH secretion, urinary nitrogen
excretion, and basal and exercise-stimulated oxygen consumption. Two protocols
were conducted, which reflect a total of 18 separate studies. In the first
paradigm, 5 healthy young men were each studied in a double blind, randomized
manner during 3 different gonadal hormone manipulations, in which serum
testosterone was varied from hypogonadal (induced by leuprolide) to eugonadal
(saline injections) to high levels (testosterone enanthate, 3 mg/kg.week, i.m.).
There was a washout period of 8 weeks between treatments. In the second protocol,
3 of the original subjects were studied after 2 weeks of treatment with
stanozolol (0.1 mg/kg.day). Two to 3 weeks after the desired changes in serum
testosterone, each subject was admitted to the General Clinical Research Center
for study. The hypogonadal state (serum testosterone, 33 ng/dL) increased urinary
nitrogen loss (by 34%; P < 0.005) and decreased basal metabolic rate (by 12%; P <
0.02) compared with the eugonadal state (testosterone, 796 ng/dL). High dose
testosterone (1609 ng/dL) further decreased urinary nitrogen loss over the
eugonadal state (by 16%; P < 0.05). Stanozolol yielded the lowest urinary
nitrogen excretion of all (P < 0.03). Like urinary nitrogen, the basal metabolic
rate showed the greatest change between the hypogonadal and eugonadal states
(12%; P < 0.02), with a lesser change during high dose testosterone treatment
(4%). Analogously, end-exercise oxygen consumption rose by 11% between the
hypogonadal and eugonadal states (P < 0.05). Between the hypogonadal and
eugonadal states, no significant changes in pulsatile (nonstimulated),
exercise-stimulated, or GRF-stimulated GH secretion or serum insulin-like growth
factor I concentrations were observed. Raising testosterone to supraphysiological
levels increased pulsatile GH secretion by 62% over that with leuprolide and by
22% over that with saline (P < 0.05). High dose testosterone treatment also
increased serum insulin-like growth factor I concentrations by 21% and 34% over
those during the eugonadal and hypogonadal states, respectively (P < 0.01).
Testosterone did not affect either exercise- or GRF-stimulated GH secretion. In
protocol 2, stanozolol did not affect any parameter of GH secretion. To examine
the interaction between GH secretion and testosterone on urinary nitrogen
excretion and basal metabolic rate, a one-way analysis of covariance was
undertaken. Statistical examination of GH production as the covariate and
testosterone (by tertile) as the interactive factor demonstrated significant
relationships between serum testosterone levels and either urinary nitrogen (P <
0.02) or basal metabolic rate (P < 0.01), but not GH secretion (P = NS). In
summary, these results demonstrate that short term modulation of the androgen
milieu affects metabolic outcome without necessitating changes in GH secretion.
These results have significance for both normal physiology and for the treatment
of hypogonadal GH-deficient patients.