The effect of administration of human growth hormone on the plasma growth hormone, cortisol, glucose, and free fatty acid response to insulin: evidence for growth hormone autoregulation in man

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.

Section: In Vivomentioning

confidence: 61%

Section: Introductionmentioning

confidence: 87%

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

Rosenthal¹,

Hulse²,

Kaplan³

et al. 1986

“…The absence of such centers in alnencephaly would, of course, preclude such a control system. Autoregulation of growth hormone secretion by growth hormone itself, another postulated mechanism for growth hormone control (33,34), would also be interfered with if the sensor is in the hypothalamus. (25).…”

Section: Resultsmentioning

confidence: 99%

Endocrine Studies in Anencephaly

Hayek¹,

Driscoll²,

Warshaw³

1973

A B S T R A C T Endocrine function has been investigated in four anencephalic neonates to determine the influence of absence of cortical and hypothalamic tissue and of hypoplasia of the pituitary. Intravenous glucose administration resulted in higher peak values for blood sugar and more rapid glucose disposal rates than reported in normals. Intravenous insulin tolerance tests on two of the infants failed to evoke elevations in plasma growth hormone, and the infants showed a remarkable resistance to the hypoglycemic effect of insulin. Administration of lysine-vasopressin caused an active growth hormone release. Similarly, there was a large increase in serum thyrotropin after administration of synthetic thyrotropinreleasing hormone. Basal levels of both thyrotropin and growth hormone were low as compared with values reported for normal newborns. Prolactin values obtained on three of the infants were in the normal range. The results strongly suggest that anterior pituitary function mediated by the hypothalamus and its releasing factors is deficient in anencephaly. However, the anterior pituitary can release growth hormone and thyrotropin when stimulated directly and, in the case of thyrotropin release, may function autonomously. The normal prolactin values presumably reflect the absence of the hypothalamic prolactin inhibitory factor.

“…Refractoriness of GH secretion to repeated stimulation by L-dopa (22) or sequential exercise and arginine infusion (23) has been previously demonstrated. Furthermore, exogenous GH administration inhibits spontaneous pulsatile endogenous GH secretion in the rat (24) and inhibits nyctohemeral (25) and insulin- (26), arginine-, or exercise-induced (23) GH secretion in man by unknown but possibly somatostatin-mediated mechanisms. GH stimulates somatostatin release from the rat hypothalamus in vitro within 20 min at a concentration of 20 ng/ ml (8).…”

Section: Discussionmentioning

confidence: 99%

Plasma growth hormone responses to constant infusions of human pancreatic growth hormone releasing factor. Intermittent secretion or response attenuation.

Webb¹,

Vance²,

Thorner³

et al. 1984

As bstract. Administration of human pancreatic tumor growth hormone (GH) releasing factor ) as a single injection to normal human subjects stimulates the secretion of GH in a dose-responsive manner. In the present studies, hpGRF(1-40) was infused in a graded stepwise manner over a 6-h period in order to determine whether the GH secretory response would be sustained. Normal adult males received four consecutive 90-min infusions of hpGRF(1-40) at doses of 1, 3.3, 10, and 33 ng/kg per min, preceded and followed by a 90-min saline infusion; and the plasma GH responses were compared with those during a separate control infusion.Plasma GH levels were significantly elevated by each hpGRF(1-40) infusion; and dose responsiveness was evident for the lowest three doses. Mean integrated GH secretory rates for the four doses were 1.95, 3.29, 4.29, and 3.65