Alpha 2-adrenergic control of growth hormone (GH) secretion in conscious male rabbits: involvement of endogenous GH-releasing factor and somatostatin.
In an attempt to clarify the regulatory role in GH secretion of central alpha-adrenergic and dopaminergic mechanisms, the effects of iv administration of alpha 1- and alpha 2-adrenergic antagonists and dopaminergic antagonists were investigated in undisturbed conscious male rabbits. During a 6-h observation period (1030-1630 h), control animals demonstrated spontaneous pulsatile GH secretion with mean (+/- SEM) 6-h GH levels of 6.49 +/- 0.54 ng/ml (n = 16). Intravenous injection of yohimbine (YOM; an alpha 2-antagonist), chlorpromazine (CPZ), and haloperidol (HAL; dopamine and alpha-adrenergic antagonists) completely suppressed this pulsatile GH secretion (mean 6-h GH levels, 2.98 +/- 0.24, 3.48 +/- 0.24, and 2.91 +/- 0.29 ng/ml, respectively; P less than 0.001), whereas prazosin (an alpha 1-antagonist), pimozide (a selective dopamine antagonist), sulpiride, and YM-09151-2 (YM; D2-specific antagonists) failed to affect the GH secretory pattern (mean 6-h GH levels, 6.61 +/- 0.73, 6.71 +/- 0.56, 5.44 +/- 0.44, and 6.87 +/- 1.44 ng/ml, respectively). While an iv injection of 2 micrograms synthetic human GH-releasing factor-(1-44)-NH2 (hGRF) induced GH rises in prazosin-, HAL-, pimozide-, sulpiride-, and YM-treated rabbits as well as control rabbits, YOM and CPZ completely abolished these GH responses to hGRF injection. An iv injection of 10 ml antisomatostatin gamma-globulin caused a prompt and transient GH rise, followed by a sustained elevation of GH trough levels in normal control rabbits. YOM treatment completely abolished this highly oscillated GH release. However, suppression by YOM or CPZ of hGRF-induced GH rises was significantly reversed by iv administration of 10 ml antisomatostatin gamma-globulin. Therefore, the inhibitory effect of YOM and CPZ on both episodic GH release and hGRF-induced GH rises is due to the enhanced release of somatostatin, with a simultaneous suppression of endogenous GRF. On the other hand, HAL, possessing a weaker alpha-blocking action than CPZ, blunted pulsatile GH secretion, but only modestly suppressed hGRF-induced GH rises. These results suggest the following. 1) Central alpha 2-adrenergic mechanisms play a more important role in the regulation of GH secretion than alpha 1-adrenergic mechanisms in the rabbit as well as in other species. 2) The alpha 2-adrenergic blockade causes suppression of the release of hypothalamic GRF and enhanced release of endogenous somatostatin, thereby suppressing GH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Minamitani
N
N
Department of Medicine, Kobe University School of Medicine, Japan.
Chihara
K
K
Kaji
H
H
Kodama
H
H
Kita
T
T
Fujita
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology / Q000031:analogs & derivatives; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010507:Periodicity; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013004:Somatostatin / Q000276:immunology; D015016:Yohimbine / Q000494:pharmacology; D005719:gamma-Globulins / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D018492:Dopamine Antagonists; D010446:Peptide Fragments; D011942:Receptors, Adrenergic, alpha; D005719:gamma-Globulins; C040786:somatotropin releasing hormone (1-44)amide; D015016:Yohimbine; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D006220:Haloperidol; D002746:Chlorpromazine; D004298:Dopamine