Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR-/-mice

Abstract

Global disruption of the GH receptor in mice (GHR-/-) produces a large and reproducible extension in lifespan. Since lack of GH action in muscle resulting in improved glucose homeostasis is potentially a mechanism by which GHR-/- mice are long-lived, and since no information on muscle-specific GHR disruption in females is available, we generated and characterized a line of muscle-specific GHR disrupted (MuGHRKO) mice. As expected, male MuGHRKO mice had improved fasting blood glucose, insulin, c-peptide, and glucose tolerance. In contrast, female MuGHRKO mice exhibited normal glucose, insulin, and glucose tolerance. Body weight was mildly but significantly altered in opposite directions in males (decreased) and females (increased) compared to controls. Grip strength and treadmill endurance were unchanged with advanced age in both sexes, suggesting that the direct action of GH on muscle has minimal effect on age-related musculoskeletal frailty. Longevity was unchanged in both sexes at Ohio University and significantly increased for males at University of Michigan. These data suggest that removal of GHR in muscle of male MuGHRKO mice replicates some of the health benefits seen in global GHR-/- mice including improvements to glucose homeostasis and smaller body weight in males, which may explain the trends observed in lifespan.