Attenuation of Clonidine-lnduced Growth Hormone Release following Chronic Glucocorticoid and 5-Hydroxytryptamine Uptake-Inhibiting Antidepressant Treatments

Abstract

Administration of various doses of clonidine increased plasma growth hormone levels in male Wistar rats. Chronic hydrocortisone treatment produced significant decreases in ACTH levels as well as a significant attenuation of clonidine-induced increases in growth hormone levels. Similarly, chronic treatment with 5-HT uptake-inhibiting antidepressants such as fluoxetine, clomipramine and imipramine also significantly attenuated clonidine-induced increases in growth hormone levels. On the other hand, chronic treatment with clorgyline (monoamine oxidase type A-inhibiting antidepressant) and 5-HT agonists, such as m-chlorophenylpiperazine, 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane and 8-hydroxy-2-(di-n-propylamino)tetralin, did not have any significant effect on clonidine-induced increases in growth hormone levels. These findings suggest the development of functional subsensitivity of either α₂-adrenergic heteroreceptors or 5-HT_1C receptors mediating clonidine-induced growth hormone secretion following chronic treatment with glucocorticoids and 5-HT uptake inhibitors.

Norepinephrine Regulation of Growth Hormone Release from Goldfish Pituitary Cells. I. Involvement of α2 Adrenoreceptor and Interactions With Dopamine and Salmon Gonadotropin‐Releasing Hormone

“…In mammals, especially in the rat, norepinephrine stimulates GH release through α 2 adrenoreceptors in the hypothalamus by inducing GHRH release from the arcuate nucleus (ARC; ( 27)) and inhibiting somatostatin secretion from the periventricular nucleus ( 28, 29). In the same animal model, α 2 adrenergic stimulation of GHRH release requires an intact serotoninergic system in the ARC ( 30) and α 2 adrenoreceptors have been identified in the nerve terminals of serotonin neurones ( 31). These findings raise the possibility that GHRH release induced by β 2 adrenergic stimulation is indirect and mediated through serotonin interneurones.…”

Modified Clonidine Testing for Growth Hormone Stimulation Reveals α2-Adrenoreceptor Sub Sensitivity in Children with Idiopathic Growth Hormone Deficiency

“…In contrast to constitutional growth delay, idiopathic isolated growth hormone deficiency and small for gestational age seem to display attributes of a “stress” disease independent from actual psychosocial stress due to short stature, which is equal in these groups. A functional α 2 -adrenoreceptor sub sensitivity mediating clonidine induced growth hormone secretion has been described in Wistar rats after chronic hydrocortisone treatment simulating stress [ 28 ]. A link between diurnal cortisol rhythms and child growth was shown in a longitudinal study exploring the life history consequences of hypothalamic pituitary axis in children of a foraging society in the Bolivian Amazon [ 29 ].…”