The release of growth hormone (GH) in mammals occurs in a pulsatile manner, which is critical for its physiological functions: essential during early puberty and growth, and crucial in maintaining metabolic balance during adulthood. Hypothalamic GH releasing hormone (GHRH) and somatostatin maintain the pulsatile release of GH. Metabolic regulatory hormones, ghrelin, leptin and insulin, also regulate GH pulsatile release from pituitary somatotrophs.
In mouse, GH pulsatile patterns from early-puberty (5 weeks) to post-puberty age (10 weeks) become more regular and less frequent without total GH difference. In early-adulthood (12-16 weeks), GH pulsatile and total secretions are reduced with increase in age. To characterize the impact of dietary induced weight gain (DIWG) and increased adiposity on the post-pubertal decline of GH in mice, pulsatile GH secretion at 12 and 16 weeks of age in normal and 4-8 weeks of high fat feeding (HFF) was analyzed showing reduced GH secretion. In addition to GH, circulating levels of leptin, insulin, glucose, free fatty acids, and liver triglycerides at 16 weeks were also assessed. HFF resulted in an increase in adiposity and leptin levels, liver triglycerides, glucose intolerance and hyper-insulineamia. Pulsatile GH profile in HFF 12 weeks of age was similar to that in normal feeding 16 weeks. It is also evidenced that reduction in GH pulsatile release occurred even before weight gain or HFF but correlated closely with body adipose tissues.
Observations suggest that GH pulsatile regulation is established in early puberty time and amplitudes of pulse are reduced along age after puberty; this post-puberty decline in GH is facilitated by DIWG with increased adiposity in mice. Further, reduced GH secretion occurs before DIWG indicating causative role to obesity. Given the established role of GH on post-pubertal somatic development, we anticipate that reduced GH secretion with dietary induced weight gain and increased adiposity will have long-term ramifications on adult health and ageing process.
Supported by NHMRC and The University of Queensland.