Endocrine Abstracts

Reports dating back to the 1950s have implicated human Growth Hormone (GH) in the initiation and invasive progression of several types of human cancers. A major hurdle in treating cancer is resistance to therapy. Recently, through a series of mechanistic studies using in vitro models and in silico analyses of human cancer patient databases, we have identified a covert role of GH in promoting cancer drug resistance via direct upregulation of: (i) the expression of ATP-...

The effects of conditional mouse growth hormone receptor gene disruption or ‘knock-out’ on metabolic parameters and longevity will be presented. Tissues investigated include muscle, adipose, heart, and liver. Also, data on adult onset growth hormone gene disruption will be presented....

GH receptor-binding protein gene disrupted mice GHR(−/−) are dwarf, obese, insulin sensitive, and long-lived whereas GH transgenic mice are giant, glucose intolerant, lean, and short lived. When challenged with a high-fat (HF) diet, all mice became hyperinsulinemic with similar percent weight gains and increases in percent body fat and size of the epididymal, retroperitoneal, and subcutaneous fat depots. For GH mice, the increase in adipose tissue was relatively sm...

In this talk I will describe several genes that have been implicated in the action of GH as it relates to aging. Much of the data is derived from two dwarf and one giant strain of mice produced in our laboratory that possess very different life spans. One of the dwarf lines contains a disruption of the GH receptor and binding protein gene (GHR/BP) (PNAS, 94:13215–13220, 1997). Homozygous GHR/BP ‘knockout’ mice (GHR/BP−/−) show severe postnatal growth...

In this lecture, fundamental concepts in the area of molecular biology will be presented. These include biology’s and biotechnology’s central dogma; the ‘human genome project’; the discordance between human gene number and corresponding protein number; and gene cloning techniques. Also presented will be procedures used to determine gene number and location (Southern blotting) and levels of gene expression at the RNA (Northern blotting, reverse transcription...

GH influences multiple metabolic pathways. Excess GH (acromegaly) causes a distinct form of cardiomyopathy, which may progress to fulminant heart failure. AMPK is an energy conservation enzyme that modulates multiple areas of the cell stress response, inhibiting anabolism and promoting catabolism. AMPK is activated by phosphorylation at Thr172 and measurement of Thr172 phosphorylation is thought to correlate with enzyme activity. We investigated the influence of GH on cardiac ...

GH is an important anabolic hormone involved in the regulation of longitudinal bone growth. However, acromegaly patients have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that overexpression of GH has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyse the effects of high serum GH levels on bone architecture and mechanical strength. Five month-old hemizygous male bGH...

Patients with growth hormone deficiency (GHD) have many clinical features in common with Cushing’s syndrome (glucocorticoid excess) - notably visceral obesity, insulin resistance, osteoporosis and increased vascular mortality. Within key metabolic tissues, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to the active glucocorticoid, cortisol, and thus amplifies local glucocorticoid action. We hypothesise that 11β-HSD1 expression is neg...

Growth hormone (GH) responsive cells are extensively distributed in central nervous system, including in neurons of the arcuate (ARH) and ventromedial nucleus (VMH) of hypothalamus, areas that control food intake, energy expenditure and blood glucose. During metabolic stresses, such as food restriction and hypoglycemia, GH secretion is stimulated and may be important to maintain survival. In the present study, we first verified that an acute GH injection stimulates food intake...

Growth hormone receptor (GHR) defective Laron Syndrome (LS) has been treated with daily subcutaneous recombinant insulin-like-growth factor 1 (IGF1) injections lasting many years. We have reported the results of treatment of 4-5 week old Laron dwarf mice (GHR-/-) with a single injection of an adeno-associated virus vector with a murine GHR (AAV-GHR) and a liver specific promoter at a dose of 4 × 1010 vector genome per mouse (Sia et al, Gene Therapy 202...