Changes in Hypothalamic-pituitary-growth Hormone (GH) Axis by Fasting: Study on the Differences between Male and Female Rats / 대한내분비학회지

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.