HIV GP120 INHIBITS THE SOMATOTROPIC AXIS - A POSSIBLE GH-RELEASING HORMONE-RECEPTOR MECHANISM FOR THE PATHOGENESIS OF AIDS WASTING

AIDS is often associated with growth retardation in children and wasti ng in adults, The dissociated envelope protein of the HIV (HIV-1), gp1 20, can be found in significant concentrations in the parenchyma and c erebrospinal fluid of brains in infected individuals, even in the earl iest stages of HIV-1 disease. On the basis of this and the fact that w e observed pentapeptide sequence homology between GH-releasing hormone (GHRH) and the V2 receptor-binding region of gp120, we initiated expe riments to determine whether gp120 could affect GH secretion and growt h in vivo and/or interact with anterior pituitary GHRH receptors in vi tro. Although acute IV administration of gp120 in conscious rats had n o effect on plasma GH levels, acute administration of gp120 (400 ng) i nto the brain significantly suppressed pulsatile GH release over a 6-h period compared with saline-injected controls, Furthermore, the putat ive gp120 antagonist, Peptide T (DAPTA), prevented the suppression of GH by gp120, In support of these in vivo findings, gp120 also signific antly (P < 0.05) suppressed GHRH-stimulated GH release in static cultu res of dispersed pituitary cells and from cells undergoing perifusion with the peptides, DAPTA prevented the GH suppression by gp120 in both of the pituitary cell paradigms, Furthermore, chronic administration of gp120 into the third ventricle significantly reduced body weight in juvenile rats, compared with saline-injected controls, Thus, gp120 ap pears to act both at the hypothalamus and pituitary to suppress GH rel ease, and its action at these two locations is associated with a signi ficant loss in body weight in chronically treated young animals, These findings may suggest a specific mechanism for the pathogenesis of was ting in HIV-1 patients that involves blockade of endogenous GHRH recep tors by gp120.