The major function of the ubiquitin-conjugating system is the targeting of cytosolic and nuclear proteins for degradation by the proteasome. Recently, ubiquitin conjugation has been implicated in the downregulation of signalling receptors such as the mammalian growth hormone receptor (GHR) and the alpha-factor receptor in yeast. By examining truncated receptors, the internalization-deficient re...

GH receptor (GHR) has been reported to express in both normal rat and human adrenals. However, no study examined GHR expression in diseased human adrenal cortex. We quantitated, with RT-PCR, GHR messenger RNA (mRNA) in both normal and diseased human adrenal cortex with the following results: GHR mRNA levels in four histologically normal, not steroid-stimulated, control adrenal cortices was 1.5-...

Growth hormone receptor (Ghr) signaling is important in a wide variety of cellular processes including aging; however, the role of Ghr signaling in hematopoietic stem cell (HSC) biology remains unexplored. Within the hematopoietic system, Ghr is expressed in a highly HSC-specific manner and is significantly upregulated during aging. Exposure of young and old HSCs to recombinant growth hormone e...

We have previously shown that growth hormone (GH) overexpression in the brain increased food intake, accompanied with increased hypothalamic agouti-related protein (AgRP) expression. Ghrelin, which stimulates both appetite and GH secretion, was injected intracerebroventricularly to GHR-/- and littermate control (+/+) mice to determine whether ghrelin's acute effects on appetite are dependent on...

Prostate cancer is the most common of any nonskin cancer in the human body. Some recent clinical and epidemiologic studies suggest that the growth hormone/insulin-like growth factor-I (GH/IGF-I) axis may influence prostate carcinogenesis. The purpose of this dissertation study was to establish the first animal models to directly test the hypothesis that a normal, functional GH/IGF-I axis is req...

BACKGROUND A genomic deletion of exon 3 (d3-GHR) of the growth hormone (GH) receptor (GHR) has been linked to the effectiveness of GH therapy in children with GH deficiency. Carriers of the d3-GHR genotype had higher GH-induced growth rates than children homozygous for the full-length (fl)-GHR. The aim of this study was to test whether the relationship between GH and insulin-like growth factor-...

Prolactin, glucocorticoids, and insulin are commonly used to induce milk protein synthesis in bovine mammary cell cultures. In addition, administration of GH increases milk yield in dairy cows, likely via the mammalian target of rapamycin (mTOR) pathway and IGF-I synthesis. As such, the hypothesis of this study was that mRNA abundance of hormone receptors, mammalian target of mTOR pathway-relat...

The growth hormone receptor (GHR) intracellular domain contains all of the information required for signal transduction as well as for endocytosis. Previously, we showed that the proteasome mediates the clathrin-mediated endocytosis of the GHR. Here, we present evidence that the proteasomal inhibitor MG132 prolongs the GH-induced activity of both GHR and JAK2, presumably through stabilization o...

BACKGROUND Mutations localized in the Growth Hormone Receptor (GHR) gene are often associated with the pathogenesis of Laron Syndrome, an autosomal recessive hereditary disorder characterized by severe growth retardation. Biochemically, patients present normal to high circulating GH levels, in presence of very low or undetectable IGF-I levels, which do not rise after rhGH treatment. CASE PRES...