Role of Glucocorticoids in Fasting-induced Changes in Hypothalamic and Pituitary Components of the Growth Hormone (GH)-axis

Abstract

To directly test if elevated glucocorticoids are required for fasting-induced regulation of growth hormone (GH)-releasing hormone (GHRH), GHRH receptors (GHRH-R) and ghrelin receptors (GHS-R) expression, male rats were bilaterally adrenalectomized or sham operated. After 7 days, animals were fed ad libitum or fasted for 48 h. Bilateral adrenalectomy increased hypothalamic GHRH to 146% and decreased neuropeptide Y (NPY) mRNA to 54% of SHAM controls. Pituitary GHRH-R and GHS-R mRNA levels were decreased by adrenalectomy to 30% and 80% of sham-operated controls. In shamoperated rats, fasting suppressed hypothalamic GHRH (49%) and stimulated NPY (166%) mRNA levels, while fasting increased pituitary GHRH-R (391% ) and GHS-R (218% ) mRNA levels. However, in adrenalectomized rats, fasting failed to alter pituitary GHRH-R mRNA levels, while the fasting-induced suppression of GHRH and elevation of NPY and GHS-R mRNA levels remained intact. In fasted adrenalectomized rats, corticosterone replacement increased GHRH-R mRNA levels and intensified the fasting-induced decrease in GHRH, but did not alter NPY or GHS-R response. These data suggest that elevated glucocorticoids mediate the effects of fasting on hypothalamic GHRH and pituitary GHRH-R expression, while glucocorticoids are likely not the major determinant in fasting-induced increases in hypothalamic NPY and pituitary GHS-R expression.

Arrdc2 and Arrdc3 elicit divergent changes in gene expression in skeletal muscle following anabolic and catabolic stimuli

“…On the contrary, it is possible that changes in Arrdc2 expression simply represent alterations in glucocorticoid receptor activation rather than having a direct role in growth regulation. For instance, changes in glucocorticoid levels/receptor activation underlie, or have been proposed to occur with, each of the conditions analyzed herein (i.e., nutrient consumption, mechanical overload, aerobic exercise, testosterone depletion) (20,27,37,46,58). Thus, the change in Arrdc2 expression may simply provide a readout of changes in glucocorticoid receptor activation without actually contributing to growth regulation.…”

Fasting in mood disorders: neurobiology and effectiveness. A review of the literature

“…Prolonged fasting (>8 d) is a strong physiological stimulus equivalent to a biological stress, that activates the hypothalamic-pituitary-adrenal axis (HPA, said "stress axis") (Brecchia et al, 2006;Fekete et al, 2006;Kim et al, 2008;Park et al, 2004;Shahab et al, 1997;Steiner et al, 2003). The biological mechanisms of this activation are unclear and could include the reduced availability of cerebral glucose, reduced insulin and leptin levels, or the sensation of hunger (Brecchia et al, 2006;Fekete et al, 2006;Kim et al, 2008;Park et al, 2004;Shahab et al, 1997;Steiner et al, 2003).…”

“…The biological mechanisms of this activation are unclear and could include the reduced availability of cerebral glucose, reduced insulin and leptin levels, or the sensation of hunger (Brecchia et al, 2006;Fekete et al, 2006;Kim et al, 2008;Park et al, 2004;Shahab et al, 1997;Steiner et al, 2003). Change in leptin levels has been identified as a strong signal of biological adaptation of the organism to starvation, and has been associated with mood disorders (Tichomirowa et al, 2005).…”

Direct Corticosteroid Modulation of GABAergic Neurons in the Anterior Hypothalamic Area of GAD65-eGFP Mice

“…Mice were housed under conditions consisting of constant temperature and humidity and a 12 h light/dark cycle, with free access to food and water. For the electrophysiological experiment, the mice were bilaterally adrenalectomized, by dorsal approach, and 0.9% saline was provided after surgery [18]. Intact mice were used for single cell RT-PCR and immunohistochemistry to evaluate corticosteroid receptor expression.…”