Modulations Of The GH-IGH-I Axis In Rats By Hypoxia And Other Stresses

Somatic growth is genetically a programmed sequence of events, which requires the maintenance of homeostasis proceeding. Hypoxia, one of the environmental factors in plateau, is due to a lowered oxygen pressure, which leads to oxygen deficiency of the whole organism, and even in tissues and cells, consequently disturbs physiological activities and does harm to health. It is noteworthy that suppressed body growth seems to be associated with hypoxia in both human beings and animals. It has been reported that continual hypoxia acutely and chronically induced suppression in the body growth and development of rats, which may in part be correlated with an inhibition of the GH release and/or biosynthesis. In this study, we focus on the effects of hypoxia on the hypothalamo-pituitary-somatotropic (HPS) axis, which is related to the growth and development.It is believed that the growth hormone (GH) plays an important role in body's growth. GH is regulated by two hypothalamic neuropeptides: inhibitory somatostatin (SS) and stimulatory GH-releasing hormone (GHRH). Insulin-like growth factor-I (IGF-I) is a polypeptide hormone synthesized and secreted mainly by the liver. GH increases hepatic production of IGF-I and also acts on other tissues to stimulate autocrine/paracrine release of IGF-I. IGF-I also operates a feedback regulation on GH secretion. GHRH/SS, GH, and IGF-I constitute the HPS axis.The GH and IGF-I mRNA were assayed by RT-PCR. The immunostaining SS, GH, and IGF-I were tested via immunohistochemistry (IHC) and Western blot. Using stimulated hypobaric chambers, we observed the functions and changes of HPS axis when male adult rats were exposed to different altitudes of hypoxia for different time courses. The relationship between HPS axis and the body weight gain (BWG) wereABSTRACTinvestigated. Furthermore, the regulatory mechanisms of HPS axis by central neuropeptides during hypoxia stress were examined.The results are as followed:1. Effects of acute hypoxia on GH-IGF-I axis in ratsUnder hypoxia of 2km (16.0% O2, 79.97 kPa), 5km (10.8%O2, 54.02 kPa), and 7km (8.3 % O2, 41.83 kPa) for 0.5 h, the immunostaining GH in pituitary and IGF-I in liver both increased, and positively correlated with the severity of hypoxia.Acute hypoxia (5 km) enhanced immunostaining GH in pituitary for 2 h. Then, no significant difference was observed in the following 4 h and 8 h. Acute hypoxia (5 km) enhanced immunostaining IGF-I in liver for 4h and 8 h.2. Intermittent hypoxia (IH) inhibits GH-IGF-I axis in ratsIH of 2 km (IH2) did not significantly influence the BWG. IH of 5 km (IH5) noticeably resulted in a decrease of BWG. The BWG was lowered by 31.2% (P<0.01) for 2d, and 43.3% (PO.001) for 4d. Then BWG returned to control level until 15d.IH2 for 5, 10 and 15d enhanced the immunostaining GH in pituitary, and the top by 52.0% (P<0.01) occurred on day 10. When rats were exposed to IH5 for Id, GH mRNA in pituitary was not changed. The GH mRNA in the pituitary was remarkably suppressed for 2d (p<0.001) and 5d (p<0.05) under IH5. IH5 for 2, 5 and lOd increased the immunostaining GH, and the top by 71.7% (P<0.001) occurred on day 5, then it returned to control level.IH2 caused a progressed reduction and return of the immunostaining SS in ME of hypothalamus. The marked decrease (the lowest point) by 46.3% (P<0.05)?occurred on day 5. IH5 also had the similar effects, but the significant decreases of 27.7% (PO.05) and 40.0% (PO.01) took place on day 2 and day 5, respectively.IH2 for 5 and lOd enhanced the hepatic immunostaining IGF-1, then it returned to control level. IH5 for 2, 5 and lOd increased the immunostaining IGF-I, and the top occurred on day 5 (P<0.001), then the hepatic IGF-I returned to control level.3. Chronic continual hypoxia (CH) seriously inhibits GH-IGF-I axis in ratsCH of 2 km (CH2) through l-5d suppressed the BWG, and then it recovered to control level. From 14d to 25d, the BWG decreased again. CH of 5 km (CHS) noticeably resulted in a serious suppression of BWG (PO.001), which lasted...