Searchable abstracts of presentations at key conferences in endocrinology

ea0090s8.3 | GH links to cancer | ECE2023

Lessons from experimental animal models

Kopchick John

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-...

ea0049s3.2 | From the pituitary to the periphery | ECE2017

GHR: are there benefits of endocrine defects?

Kopchick John

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....

ea0035s24.2 | Nutrient regulation of metabolism and endocrine systems | ECE2014

Metabolic consequences of a high-fat diet on mouse models of GH action

Kopchick John

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...

ea0025pl3 | Society for Endocrinology Transatlantic Medal Lecture | SFEBES2011

GH, GH receptor antagonists, GH receptor ‘knock-outs’: a story of fat old mice

Kopchick John

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...

ea0020me14 | (1) | ECE2009

Molecular biology for clinicians

Kopchick John

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...

ea0099pcc2.5 | Growth Hormone Research Society (GRS) Congress (Day1) | ECE2024

Growth hormone, mini-mice, football, dirty shorts, and a new drug

Kopchick John J

The growth hormone receptor antagonist was discovered via expression of mutated GH genes in transgenic mice. Although we were attempting to generate potent GH analogs, our mouse studies indicated that the compound was ‘inhibiting’ GH action. We subsequently showed that it was a GH receptor antagonist, the first of its type. Many hurdles needed to be ‘jumped’ in the development of this compound into a drug including protection of intellectual property; fundi...

ea0025p164 | Diabetes, metabolism and cardiovascular | SFEBES2011

Chronic GH excess is associated with adenosine monophosphate-activated protein kinase (AMPK) threonine-172 phosphorylation changes that do not lead to changes in AMPK activity

Thomas Julia , List Edward , Kopchick John , Grossman Ashley , Korbonits Marta

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 ...

ea0031p8 | Bone | SFEBES2013

Excessive GH expression in bGH transgenic mice adversely alters bone architecture and quality

Lim Su-Vern , Marenzana Massimo , List Edward , Kopchick John , Korbonits Marta , Chenu Chantal

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...

ea0028p308 | Steroids | SFEBES2012

Negative regulation of 11β-HSD1 by GH in key metabolic tissues may contribute to metabolic disease in GH deficient patients

Morgan Stuart , Berryman Darlene , List Edward , Lavery Gareth , Kopchick John , Stewart Paul

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...

ea0056oc13.5 | The curious case of growth hormone | ECE2018

Growth hormone acts in AgRP neurons to control energy expenditure during food restriction and promotes counter-regulatory responses to hypoglycemia via the ventromedial hypothalamus

Furigo Isadora C , Teixeira Pryscila DS , Souza Gabriel O , List Eduard , Kopchick John , Donato Jose

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...