Mice with an RGS-insensitive Gαi2 protein show growth hormone axis dysfunction

Mice carrying an RGS-insensitive Gait mutation display growth retardation early after birth. Although the growth hormone (GH)-axis is a key endocrine modulator of postnatal growth, its functional state in these mice has not been characterized. The present study was undertaken to address this issue. Results revealed that pituitary mRNA levels for GH, prolactin (PRL), somatostatin (SST), GH-releasing-hormone receptor (GHRH-R) and GH secretagogue receptor (GHS-R) were decreased in mutants compared to controls. These changes were reflected by a significant decrease in plasma levels of GH, IGF-1 and IGF-binding protein-3 (IGFBP-3). Mutants were also less responsive to GHRH and ghrelin (GhL) on GH stimulation of release from pituitary primary cell cultures. In contrast, they were more sensitive to the inhibitory effect of SST. These data provide the first evidence for an alteration of the functional state of the GH-axis in Gai2G184S mice that likely contributes to their growth retardation.

Automated summary

Mice with an RGS-insensitive Gait mutation exhibit alterations in the functional state of the GH-axis, resulting in growth retardation. These changes include decreased pituitary mRNA levels for various hormones and reduced responsiveness to GH-stimulating agents.