With the near availability of relatively unlimited quantities of the growth promoting related hormones, hGH, somatomedin (SM), and GHRH peptides, as well as synthetic GH releasing peptides, it is reasonable to predict that a broad widespread physiologic, pharmacologic and diagnostic application of these agents will be pursued. To accomplish this objective, the following studies will be performed: determine the acute and chronic in vitro and in vivo effects of 3 GH releasing agents GH-RP-1 (a small synthetic GH releasing peptide), a kappa receptor opiate, 2549, (5,9-dimethyl-2 feet hydroxy-2-(2 methoxy propyl)-6,7 benzomorphan hydrobromide), and the GH-RH peptides (GH-RH-44 or GH-RH-40) which preliminary evidence indicates release growth hormone each by a different mechanism. Growth promoting studies will be performed primarily in rodents (rat) and these studies will be approached and designed on the hypothesis that unique in vivo differences may exist in the regulation of GH at the pituitary level and other anatomical sites of GH action in the immature and mature animal. Since GH markedly enhances milk production in cows and is a potent lactogen in primates, experiments will be performed to prove that milk production can be increased in lactating rats with these new types of GH releasing agents. The novel approach of enhancing body growth of infant rats by treating both the mother and pups with GH releasing agents will be attempted. Acute and select chronic studies will be performed in avians, ungulates, amphibians and subhuman primates to learn more about the species-dependent effects. It is predicted that in future studies with GH releasing peptides as well as human GH itself a broad variety of possible beneficial clinical effects will be investigated such as to increase body growth in children with tertiary hypothalamic GH-RH deficiency, accelerate body growth in children who have been treated previously with exogenous glucocorticoids or in hypothyroid children on thyroid hormone therapy and possibly in children with genetically determined short stature. Other clinical problems that may be helped with increased release of GH are: catabolic states, accelerated weight loss and/or decreased muscle loss in obese subjects while dieting, decreased skin thickness, select chronic anemias, decreased immunity and in the acceleration healing of nonunion fractures. Inhibition of GH secretion/with these agents may decrease the morbid complications of diabetes mellitus and improve the therapeutic results of patients with acromegalia, far advanced breast or prostate cancer.
