The antagonism of glucocorticoid inhibition of wound healing in rats by growth hormone-releasing factor.
Daily therapeutic injections of cortisone to rats will cause weight loss and impaired wound healing. Weight loss is attributed to the catabolic effect of steroid, whereas impaired healing is associated with reductions in fibroplasia and connective tissue deposition. As the major structural protein component of connective tissue is collagen, its absence is responsible for the retarded gain in wound breaking strength. Cortisone also blocks wound closure by inhibiting wound contraction. An anabolic agent such as growth hormone may antagonize the effect of cortisone on the wound healing process. Endogenous GH can be released from the pituitary by exogenous injections of growth hormone-releasing factor (GRF). Two synthetic GRF peptides, a natural 44-amino acid peptide of the human GRF sequence, GRF-44, and an N-terminally substituted analog 29 residues, GRF-29A, were studied. Each was given twice daily with a single daily injection of cortisone for a 7-day period. Concurrent administration of GRF-44 or GRF-29A and cortisone to rats had no effect on restored body weight loss or inhibited wound contraction. While GRF-44 restored collagen deposition and caused restored wound breaking strength, GRF-29A was ineffective in restoring either. GRF-44, a synthetic peptide that stimulates pituitary release of growth hormone, antagonized some of the inhibiting effect of steroid on wound repair by promoting fibroplasia and collagen deposition.
Kelley
S F
SF
Shriners Burns Institute, Massachusetts General Hospital, Boston 02114.
Felix
A M
AM
Ehrlich
H P
HP
D000818:Animals; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014945:Wound Healing / Q000187:drug effects*
D005938:Glucocorticoids; D010446:Peptide Fragments; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone