Growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) are the two hypothalamic peptides which together control growth hormone (GH) synthesis and release. This project aims: a) To explore the efficacy of GHRH and its analogues in treating GH deficiency and GH excess (acromegaly): b) to study the neuroendocrine regulation of GH secretion; and c) to define alterations of GH regulation in different physiologic states, and to determine their cause. Therapy of GH deficiency: We have established that GH deficiency is usually due to a deficiency of hypothalamic GHRH. While this disease is usually treated with GH, we have found that GHRH is also highly effective in normalizing growth velocity in these patients. Since it can be effective even with a single daily dose, GHRH may also be as practical as GH for treatment. We are now testing whether drugs which lower SRIF, which blocks GH secretion, can enhance the therapeutic effect of GHRH. Evaluation and therapy of acromegaly: We are testing a new approach to the treatment of acromegaly, a form of pituitary tumor with overproduction of GH leading to severe illness, which is not well treated by current means. GHRH is linked to an organoboron conjugate which emits radiation under exposure to neutrons. We are testing whether this compound will localize in tumor cells, and allow them to be killed selectively.
