Endocrine Abstracts

Mice with targeted deletion of GH receptor (GHRKO mice) are GH resistant, small, hypoinsulinemic, very sensitive to insulin and remarkably long-lived. We have previously reported that these animals failed to respond to calorie restriction (CR) by additional increase in insulin sensitivity or extension of longevity. Because GHRKO mice are characterized by increased adiposity and adiposity is normally associated with insulin resistance rather than sensitivity, we hypothesized th...

Complex interactions between aging and the endocrine system include an important role of hormones in mediating effects of genotype on longevity. In Caenorhabditis elegans and Drosophila melanogaster, striking extension of life span can be produced by targeted disruption (knock out, KO) of genes that control signaling pathways homologous to insulin/insulin-like growth factor signaling in mammals. In the mouse, Mus musculus, longevity is greatly increased by spontaneous and expe...

Introduction: Long-lived mice with targeted disruption of the GHRH gene (GHRH knockout; GHRHKO) constitute a unique animal model of altered somatotrophic signaling and are characterized by reduced body mass and size, low plasma IGF1 and enhanced insulin sensitivity. These features are also observed in long-lived GH receptor knockout (GHRKO) mice, characterized by increased visceral obesity that usually promotes insulin resistance. GHRKO mice have also increased subcutaneous fa...

GH receptor knockout (GHRKO) mice were produced by a targeted disruption of the GH receptor (Ghr) gene. These long-lived mice, which are GH resistant, are characterized by a greatly reduced plasma levels of IGF1 and insulin and have enhanced insulin sensitivity (these effects resemble the characteristics of animals subjected to caloric restriction (CR), which is well known experimental model to delay aging and increase lifespan).Apoptosis, or programmed ...

Chronically elevated GH levels in GH-transgenic mice derive in accelerated growth and increased body weight. These animals present increased circulating IGF-I and hepatic IGF-I mRNA levels, as well as liver enlargement due to hypertrophy and hyperplasia, which frequently progress to hepatomas as the animals age.We have previously described that the GH-induced JAK2/STAT5 signalling pathway is desensitized in the liver of transgenic mice overexpressing GH....

JAK2/STAT5 is the principal growth hormone (GH) signaling pathway related to body growth. It is positively regulated by glucocorticoid receptor (GR) and hepatocyte nuclear factor 1 (HNF-1) and downregulated by activation of tyrosine-phosphatases SHP-1,-2 and PTP-1B, and by GH-induction of suppressors of cytokine signaling (CIS/SOCS) that block GHR or JAK2, and promote internalization/degradation of signaling complexes. This pathway is desensitized in liver of adult transgenic ...

GH and IGF1 play an important role in cardiac development and function. Conditions leading to abnormal GH levels are associated with cardiovascular disease. Although acromegaly is associated with hypertension, insulin resistance, diabetes type 2 and dislipemia, several studies ascribe the heart alterations displayed by these patients to the direct action of chronically elevated GH and IGF1 levels.Given that insulin acts as a growth factor to the heart an...