HGH Effects
Actions that have been demonstrated for synthetic HGH and/or pituitary-derived
hGH include:
Skeletal Growth: GH stimulates skeletal growth in pediatric patients
with growth failure due to a lack of adequate secretion of endogenous GH
or secondary to chronic renal insufficiency and in patients with Turner syndrome.
Skeletal growth is accomplished at the epiphyseal plates at the ends of a
growing bone.
Growth and metabolism of epiphyseal plate cells are directly stimulated by
GH and one of its mediators, IGF-I. Serum levels of IGF-I are low in children
and adolescents who are GH deficient, but increase during treatment with
GH. In pediatric patients, new bone is formed at the epiphyses in response
to GH and IGF-I. This results in linear growth until these growth plates
fuse at the end of puberty.
Cell Growth: Treatment with hGH results in an increase in both the
number and the size of skeletal muscle cells.
Organ Growth: GH influences the size of internal organs, including
kidneys, and increases red cell mass. Treatment of hypophysectomized or genetic
dwarf rats with GH results in organ growth that is proportional to the overall
body growth. In normal rats subjected to nephrectomy-induced uremia, GH promoted
skeletal and body growth.
Protein Metabolism: Linear growth is facilitated in part by GH-stimulated
protein synthesis. This is reflected by nitrogen retention as demonstrated
by a decline in urinary nitrogen excretion and blood urea nitrogen during
GH therapy.
Carbohydrate Metabolism: GH is a modulator of carbohydrate metabolism.
For example, patients with inadequate secretion of GH sometimes experience
fasting hypoglycemia that is improved by treatment with GH. GH therapy may
decrease insulin sensitivity. Untreated patients with chronic renal insufficiency
and Turner syndrome have an increased incidence of glucose intolerance.
Administration of hGH to adults or children resulted in increases in serum
fasting and postprandial insulin levels, more commonly in overweight or obese
individuals. In addition, mean fasting and postprandial glucose and hemoglobin
A1clevels remained in the normal range.
Lipid Metabolism: In GH-deficient patients, administration of GH resulted
in lipid mobilization, reduction in body fat stores, increased plasma fatty
acids, and decreased plasma cholesterol levels
Mineral Metabolism: The retention of total body potassium in response
to GH administration apparently results from cellular growth. Serum levels
of inorganic phosphorus may increase slightly in patients with inadequate
secretion of endogenous GH, chronic renal insufficiency, or patients with
Turner syndrome during GH 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 these patients. Sodium
retention also occurs. Adults with childhood-onset GH deficiency show low
bone mineral density (BMD). GH therapy results in increases in serum alkaline
phosphatase.
Connective Tissue Metabolism: GH stimulates the synthesis of chondroitin
sulfate and collagen as well as the urinary excretion of hydroxyproline.
Pharmacokinetics Subcutaneous AbsorptionThe absolute bioavailability of
recombinant human growth hormone (rhGH) after subcutaneous administration
in healthy adult males has been determined to be 81±20%. The mean terminal
t1/2after subcutaneous administration is significantly longer than that seen
after intravenous administration (2.1±0.43 hr vs. 19.5±3.1 min)
indicating that the subcutaneous absorption of the compound is slow and
rate-limiting. DistributionAnimal studies with rhGH showed that GH localizes
to highly perfused organs, particularly the liver and kidney. The volume
of distribution at steady state for rhGH in healthy adult males is about
50 mL/kg body weight, approximating the serum volume. MetabolismBoth the
liver and kidney have been shown to be important metabolizing organs for
GH. Animal studies suggest that the kidney is the dominant organ of clearance.
GH is filtered at the glomerulus and reabsorbed in the proximal tubules.
It is then cleaved within renal cells into its constituent amino acids, which
return to the systemic circulation. |