Growth Hormone Responses to Continuous Infusions of Growth Hormone-Releasing Hormone*

Abstract

The pattern of GH secretion during a continuous 4-h iv infusion of 1 microgram/kg.h GH-releasing hormone (1-44)-NH2 (GHRH-44) or saline was examined in 15 adult men. There was prompt release of GH beginning within 20 min of starting the GHRH-44 infusions, reaching peak GH levels of 43 +/- 11 (+/- SE) ng/ml within 60-90 min. This is similar to the peak GH level reached in men after a single 1 microgram/kg GHRH iv bolus dose (34 +/- 8 ng/ml). GH levels then fell progressively, but did not return to baseline during the GHRH infusions. After GHRH infusions, the response (delta) to a 1 microgram/kg GHRH bolus dose was markedly attenuated (delta GH, 2.7 +/- 0.9 ng/ml) compared to the response (delta GH, 23 +/- 3 ng/ml) after saline infusion. Dispersed rat pituicytes perifused with medium containing 10 nM GHRH-44 responded with an initial rapid rise in GH secretion, followed by a progressive decline, and after 150 min of continuous GHRH exposure, the response to pulses of an equal or higher (100 nM) GHRH concentration was blunted. These results indicate that the peak response to GHRH infusions is similar to that of maximally effective bolus doses; during infusions, the GH response is not sustained; and immediately after GHRH infusions, the response to previously effective bolus doses is reduced. These phenomena could reflect either receptor-mediated desensitization, the depletion of rapidly releasable GH stores, or both. A counterregulatory rise in hypothalamic somatostatin secretion is not necessary to produce these effects, since the same phenomenon occurs in vitro and in vivo.

lntra‐ and Inter‐Individual Variability in Growth Hormone Responses to Growth Hormone‐Releasing Hormone*

“…Although our results do not indicate the mechanism for this variability, they are consistent with the belief that fluctuations in hypothalamic SRIF secretion may variably modulate GH responses to GHRH stimulation (1 1). A similar phenomenon is observed in GH levels measured during the continuous infusion of GHRH: secretion of G H is increased overall, but continues to be pulsatile during the infusions, indicating ongoing variability in another modulator, which is most likely SRIF (9). Recently, Mazza and colleagues have noted that the GH response to GHRH is both increased and made less variable by co-administration of the drug pyridostigmine, which potentiates cholinergic tone, which in turn is believed to decrease SRIF secretion (13).…”

“…The range of GH responses in normal subjects varies from very brisk to barely detectable, a far greater variability than that observed with administration of any other hypothalamic releasing factor. This high inter-individual variation in responses appears to be independent of the dose injected, and has also been reported after iv infusion of GHRH (9). Some of this variability may be attributable to differences in factors such as body weight (lo), but much occurs between individuals who do not appear to differ in any clinically important features (1, 7, 8).…”

Time- and dose-dependent responses of brain histamine to intracerebroventricular and intraperitoneal administrations of growth hormone-releasing factor (GRF1-44).

“…This is partially in agreement with the fact that although GRF stimulates the release of HA in the HhS, the repeated administration of the neuropeptide does not alter the total amount of H-1 receptors (Table 3). Desensitization to GRF associated with down-regulation of GRF-binding sites ) cannot be ruled out, because chronic exposure of the pituitary to maximum concentrations of GRF causes partial loss of responsiveness in vivo (Gelato et al 1985 ;Wehrenberg et al 1986) and in vitro (Bilezikjian and Vale 1984). However, in our studies neither single nor repeated doses of GRF affected [3H] -mepyramine binding in different regions of the HhS where i.p.…”

Growth Hormone Response to a Growth Hormone-Releasing Hormone Stimulation Test in a Population-Based Study following Cranial Irradiation of Childhood Brain Tumors

“…However, not only the administered dose but also variations in receptor sensitivity of the somatotrophs to GHRH probably have influenced the degree of pituitary stimulation. We have used a recommended standard dose of GHRH [27, 28, 29], but in other papers twice or even higher doses of GHRH were administered [4, 30]. Since we in the present study only used 1 µg/kg GHRH, the significant increase in peak GH response to GHRH stimulation compared to the response to ITT/arginine emphasized that many of the patients might have a hypothalamic rather than a pituitary damage.…”