Journal of Korean Endocrine Society 2002;17(4):473-485.
Published online August 1, 2002.
Changes in Hypothalamic-pituitary-growth Hormone (GH) Axis by Fasting: Study on the Differences between Male and Female Rats.
Sookjin Sohn, Mina Lee, Seungjoon Park
1Department of Pharmacology, School of Medicine, Kyunghee University, Seoul, Korea.
2Graduate School of East and West Medical Science, Kyunghee University, Seoul, Korea.
3Endocrine Research Institute, Kyunghee University, Seoul, Korea.
Abstract
BACKGROUND
Fasting has a profound impact on GH synthesis, and is released in all mammalian species that have been studied. The male rat has long been used as a model to determine the mechanism on how fasting mediates these changes. However, many aspects of GH synthesis, release and function are known to be gender-dependent. This study was conducted in order to determine if changes in the GH-axis, in response to fasting, differs between the sexes. METHODS: Male and female rats (8~9 weeks; n=5/group) were fasted for 72h, or supplied food ad libitum. The mean circulating serum GH and IGF-I concentrations were measured by radioimmunoassay. The levels of hypothalamic GH-releasing hormone (GHRH), somatostatin (SRIF), neuropeptide Y (NPY) and pituitary GH mRNA were measured using an RNase protection assay. The levels of pituitary GHRH receptor (GHRH-R), GH secretagogue (GHS) receptor (GHS-R) and SRIF receptor (sst1-5) mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Fasting resulted in a comparable weight loss in both the males and the females, (18.0+/-0.9%) and (17.0 0.8%), respectively. In the fasted males, there was a characteristic decrease in the serum GH (98 60 vs. 7 4 ng/mL) and IGF-I (367 35 vs 152 12 ng/mL), associated with a decrease in the hypothalamic GHRH, and an increase in the NPY mRNA, levels of 52 6% and 138 6%, respectively, compared to those of the fed controls (p<0.05). In spite of the reduction in the GHRH, fasting did not alter the levels of the pituitary GH mRNA, and in fact increased the expression of the pituitary receptors, GHRH-R and GHS-R, to 185 15 and 169 25%, respectively, to those of the fed controls. In contrast to the positive impact of fasting on the GH-stimulatory receptors, fasting led to a dramatic decrease in the expressions of the somatostatin receptor subtypes, sst2 (29+/-5% of Fed) and sst4 (60+/-7% of Fed). Fasting had comparable effects on the GH-axis of the female rats, with two notable exceptions; first, fasting did not suppress the mean circulating GH levels (16 3 vs. 38 28 ng/mL) and second, did not alter the sst2 and sst4 expressions. CONCLUSION: These results corroborate the other reports regarding the effects of fasting on the expressions of hypothalamic neuropeptides, pituitary GHRH-R and sst2, in male rats. This is the first report demonstrating that fasting stimulates the expression of pituitary GHS-R in both sexes. This is of great interest given the fact that ghrelin, the putative GHS-R ligand, is also elevated by fasting. We propose that the upregulation of both ghrelin and GHS-R may play important roles in increasing the sensitivity of the pituitary to GHRH, in that these GH-stimulatory systems work synergistically. These changes may compensate for the fasting-induced suppression of hypothalamic GHRH input. We might speculate that such compensatory mechanisms are dominant in the female rat, in that circulating GH levels are not suppressed by fasting.
Key Words: Fasting, Growth hormone, Hypothalamus, Pituitary
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