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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 sham-operated 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.
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Fig. 1.
Comparison of the body weight (A) and plasma corticosterone levels (B) of sham-operated (Sham) and adren-alectomized (ADX) animals and effect of adrenalectomy on hypothalamic (C) and pituitary (D) gene expression. Body weight was displayed % of change between immediately before operation and immediately before sacrifice. Serum corticosterone was measured by ELISA. Hypothalamic and pituitary gene expressions were measured by real-time RT-PCR. Data are mean±S.E.M., n=5 animals/group. ∗p<0.05.
Fig. 2.
Effect of fasting on body weight (A, B), serum glucose (C), circulating growth hormone (GH) (D), insulinlike growth factor (IGF)-1 (E) and corticosterone (F) in sham-operated (Sham) and adrenalectomized (ADX) rats. Serum glucose levels were measured by GlucoDr Blood Glucose Meter. Serum GH concentrations were measured by GH RIA. Serum IGF-1 and corticosterone levels were measured by ELISA. Values are expressed as mean±SEM., n=5 animals/group. ∗, indicates values differ from respective fed controls; ∗, p< 0.05.
Fig. 3.
Effect of fasting on hypothalamic neuropeptide Y (NPY), growth hormone-releasing hormone (GHRH), and somatostatin (SRIH) mRNA levels in sham-operated (A) or adrenalectomized (B) animals. Animals were fasted for 24 h, 48 h, 72 h or supplied food ad libitum (fed). Both groups were allowed free access to water or 0.9% NaCl solution (adrenalectomized group). Hyperthalamic mRNA levels were measured by real-time RT-PCR and adjusted with β-actin. The graph is expressed as a percentage of fed controls. Data are mean±S.E.M., n=5 animals/group. ∗, indicates values differ from respective fed controls; ∗, p< 0.05.
Fig. 4.
Effect of fasting on pituitary growth hormone (GH)-releasing hormone receptor (GHRH-R) (A), GH secretagogue receptor (GHS-R) (B), and GH (C) mRNA levels in adrenalectomized or shamoperated animals. Animals were fasted for 24 h, 48 h, 72 h or supplied food ad libitum (fed). Both groups were allowed free access to water or 0.9% NaCl solution (adrenalectomized group). GHRH-R, GHS-R, and GH mRNA levels were measured by real-time RT-PCR and adjusted with β-actin. The graph is expressed as a percentage of fed controls. Data are mean±S.E.M., n=5 animals/group. ∗, indicates values differ from respective fed controls; ∗, p<0.05.
Fig. 5.
Effect of corticosterone (C) on pituitary (A) and hypothalamic (B) gene expression in adrenalectomized animals. Animals were fasted for 48 h or supplied food ad libitum (fed). Subsets of fed or 48 h fasted rats were provided with 40μg/ml of corticosterone containing water from immediately after operation to immediately before sacrifice. Hypothalamic and pituitary mRNAs were measured by real-time RT-PCR. Data are mean±S.E.M., n=5 animals/group. ∗, indicates values differ from respective fed controls; ∗, p<0.05, #, p< 0.05.
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