Somatrem

Somatrem - as well as endogenous growth hormone - binds to dimeric growth hormone (GH) receptors located within the cell membranes of target tissue cells resulting in intracellular signal transduction and a host of pharmacodynamic effects. Some of these pharmacodynamic effects are primarily mediated by insulin like growth factor (IGF-1) produced in the liver and also locally (ie. skeletal growth, protein synthesis), while others are primarily a consequence of the direct effects of somatropin (ie. lipolysis).

Skeletal growth is accomplished at the epiphyseal plates at the ends of growing bone. Growth and metabolism of epiphyseal plate cells are directly stimulated by GH and its mediator IGF-I. Serum levels of IGF-I are low in children and adolescents who are growth hormone deficient, but increase during somatrem treatment. New bone is consequently formed at the epiphyses for paediatric patients in response to GH and IGF-I from somatrem treatment. This results in linear growth until these growth plates fuse at the end of puberty.

Somatrem treatment also causes an increase in both the number and the size of skeletal muscle cells. Additionally, such therapy also influences the size of internal organs, including kidneys, and increases red cell mass.

Linear skeletal bone growth is facilitated in part by GH-stimulated protein synthesis. This is demonstrated by nitrogen retention as reflected by a decline in urinary nitrogen excretion and blood urea nitrogen (BUN) during somatrem therapy. GH also acts as a modulator of carbohydrate metabolism which may improve a fasting hypoglycaemia feeling that some patients with inadequate GH secretion sometimes experience. Additionally, somatrem administration may decrease insulin sensitivity, resulting in increased serum fasting and postprandial insulin levels - usually more commonly in overweight or obese individuals, adults or children. Moreover, mean fasting and postprandial glucose and hemoglobin A1C levels remained in the normal range.

Furthermore, in growth hormone deficient patients, the use of somatrem resulted in lipid mobilization, reduction in body fat stores, increased plasma fatty acids, and decreased plasma cholesterol levels. Serum levels of inorganic phosphorus may increase slightly in patients with inadequate secretion of endogenous GH, chronic kidney disease, or Turner syndrome during somatrem therapy due to metabolic activity associated with bone growth as well as increased tubular reabsorption of phosphate by the kidney. Serum calcium is not significantly altered in somatrem patients. Sodium retention and increases in serum alkaline phosphatase can occur to patients taking somatrem. As well, GH can stimulate the synthesis of chondroitin sulphate and collagen as well as the urinary excretion of hydroxyproline.