Ghrelin and Growth Hormone Secretagogue Receptor Expression in Mice during Aging

Abstract

In well-nourished humans, GH and IGF-I decline during aging, and the responsiveness of the GH axis to exogenous ghrelin is attenuated with age. Intriguingly, the GH/IGF-I axis is rejuvenated by chronic treatment with the ghrelin mimetic MK-0677, resulting in improvements in body composition, suggesting that frail elderly subjects might benefit from treatment with ghrelin and ghrelin mimetics. Mouse models are widely used to study the effects of ghrelin, but the impact of age on the ghrelin pathway is unclear. In this study, total and active ghrelin peptides were measured in plasma, and ghrelin mRNA was quantitated in brain tissue from different aged C57BL/6J mice. Surprisingly, plasma levels of ghrelin peptide slightly increased with age; ghrelin mRNA levels were similar in brains from mice aged 2, 6, 12, and 28 months but higher in mice aged 18 and 24 months. The tissue distribution of Ghsr1a mRNA (ghrelin receptor) was also characterized, and pituitary and brain exhibited the highest levels of expression. In the pituitary gland, the highest concentration of Ghsr1a mRNA was observed at age 1-2 months, it was lower at 6 months, and remained unchanged for up to 30 months of age. This result is consistent with the finding that GH release in response to exogenous ghrelin was not significantly different in mice aged 7-30 months. In the brain, Ghsr1a mRNA levels remained stable during aging. Hence, in C57BL/6J male mice, aging is not associated with changes in circulating ghrelin levels or changes in ghrelin receptor expression in the pituitary gland and brain.