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Leptin and orexin
Obesity research has shown that there are several important factors in the human body, which control our metabolic levels. Leptin, the most notable recent discovery, is a hormone secreted from fat cells, which acts on the brain to reduce food intake and increase peripheral energy expenditure. Orexin, in the other hand, has been shown as a novel hypothalamic peptide stimulating appetite and feed intake. There is increasing evidence to support a tight link between leptin levels and various pituitary functions, including the regulation of metabolic levels of the body. As leptin, orexin and GH regulate body weight and fat/muscle ratio; we have investigated the relationship between these three hormones from fat, brain and pituitary gland. It was found that long-term in vitro leptin treatment reduced GHRH stimulated GH release from ovine somatotropes. The mechanism for such a reduction in GH release is due to a decrease in synthesis of GH, and GHRH receptor by leptin treatment. The treatment of cells with leptin however increased the synthesis of GHS receptor in somatotropes, which suggests a possible clinic use of synthetic GHS in the treatment of GH deficiency in obesity. We are now extending our research in this area to signalling systems and the molecular mechanism of the action of leptin. We also found that orexin acted on somatotropes leading to an increase in Ca2+ influx via voltage-gated Ca2+ channels. Although orexin itself did not change GH secretion from cultured somatotropes, it significantly enhanced the stimulating effect of GHRH on GH release. This is an interesting observation and the physiological and pathophysiological implications warrant further investigation.
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