Exogenous growth hormone inhibits growth hormone-releasing factor-induced growth hormone secretion in normal men.

Abstract

Previous studies from this laboratory and by others in rats, monkeys, and humans support the concept that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism. With the availability of human growth hormone-releasing factor (GRF), the possible existence of such a mechanism was reexplored by examining the effect of exogenous GH on the GH response induced by GRF-44-NH2 in six normal men (mean age, 32.4 yr). In all subjects the plasma GH response evoked by GRF-44-NH2 (1 ag/kg i.v. bolus) was studied before and after 5 d of placebo (1 ml normal saline i.m. every 12 h), and then before and 12 h after 5 d of biosynthetic methionyl human GH (5 U i.m. every 12 h). The GH response to GRF (maximal increment over time 0 value) was significantly inhibited after GH treatment (0-13 vs. 23-11.2 ng/ml before treatment, P = 0.05), but was not significantly affected by placebo. This impaired pituitary response to GRF persisted for at least 24 h following exogenous GH treatment in two subjects who underwent further study. Serum somatomedin-C concentrations were significantly increased after 5 d of GH treatment (2.66-5.00 vs. 0.92-1.91 U/ml before treatment, P = <0.01). The impaired pituitary response to GRF may be mediated indirectly through somatomedin, somatostatin, by a direct effect of GH on the pituitary somatotropes, or by all of these mechanisms. These data suggest that after GH treatment, the blunted GH response to synthetic GRF is not solely a consequence of the inhibition of hypothalamic GRF secretion.

Growth Hormone Response to a Bolus Injection of 1-44 Growth-Hormone-Releasing Hormone in Very Short Children with Intrauterine Onset of Growth Failure

“…This is in contrast with the data obtained in normal adult males, whose GH release after a bolus injection of GHRH was inhibited at the end of 5 days of GH administration [ 15] or suppressed after 4 h of venous infusion of GH [ 16], It contrasts also with the results obtained by Hanew et al [17] in 7 children considered as 'short normal', submit ted to 1-44 GHRH bolus injection of 100 pg before and 2 days after being given a single dose of 4 IU of GH, with significantly lower GH responses at the second test. Thus, the sensitivity of the feedback mechanisms which regulate the pituitary content of GH and/or its release by GHRH could be different in IUGR children from what they are in normal adults or in other short children.…”

Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion.

“…This pattern of GH secretion is different from that observed with gonadotropin secretion in subjects given gonadotropin-releasing hormone (GnRH) infusions. Infusion of GnRH results in biphasic release of LH and follicle-stimulating hormone with failure to return to base-line levels until apparent depletion or desensitization has occurred Pulsatile Growth Hormone Secretion during 24 produced by the infusion. We believe this is unlikely based upon our previous infusion studies in which we were able to demonstrate GH stimulation at a dose of 1.0 ng/kg per min (4).…”

“…These findings are consistent with the hypothesis that changes in hypothalamic and/or pituitary somatostatin concentrations are responsible for preservation of intermittent pulsatile GH secretion during hGRF-40 infusion. The elegant in vivo studies of Tannenbaum and Ling (16) (24). Thus, it is quite possible that GH feedback contributes to the reduced response of the supramaximal intravenous bolus injection, but this is likely mediated through somatostatin.…”

Nature of Altered Growth Hormone Secretion in Hyperthyroidism*

“…Thus, although decreased plasma insulin and/or IGF-I concentrations were postulated to trigger the increase in pulsatile GH release that occurs in poorly controlled type I diabetes mellitus and during prolonged fasting in normal men (18,19), the present findings in hyperthyroidism cannot be interpreted in this manner. However, we cannot exclude the considerations that hyperthyroidism alters IGF-I binding to one or more of its plasma transport proteins and/ or reduces hypothalamo-pituitary sensitivity to the negative feedback actions of IGF-I or insulin on GH secretion (31,32). Another possible mechanism, such as an expanded distribution volume for GH in thyrotoxic men, would require a 3-to 4-fold increase in the GH distribution space to account for the calculated rise in GH secretion rate.…”