HIV gp120 inhibits the somatotropic axis: A possible GH-releasing hormone receptor mechanism for the pathogenesis of AIDS wasting

Abstract

AIDS is often associated with growth retardation in children and wasting in adults. The dissociated envelope protein of the HIV (HIV-1), gp120, can be found in significant concentrations in the parenchyma and cerebrospinal f luid of brains in infected individuals, even in the earliest stages of HIV-1 disease. On the basis of this and the fact that we observed pentapeptide sequence homology between GH-releasing hormone (GHRH) and the V2 receptorbinding region of gp120, we initiated experiments to determine whether gp120 could affect GH secretion and growth in vivo and͞or interact with anterior pituitary GHRH receptors in vitro. Although acute IV administration of gp120 in conscious rats had no effect on plasma GH levels, acute administration of gp120 (400 ng) into the brain significantly suppressed pulsatile GH release over a 6-h period compared with salineinjected controls. Furthermore, the putative gp120 antagonist, Peptide T (DAPTA), prevented the suppression of GH by gp120. In support of these in vivo findings, gp120 also significantly (P < 0.05) suppressed GHRH-stimulated GH release in static cultures 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 appears to act both at the hypothalamus and pituitary to suppress GH release, and its action at these two locations is associated with a significant loss in body weight in chronically treated young animals. These findings may suggest a specific mechanism for the pathogenesis of wasting in HIV-1 patients that involves blockade of endogenous GHRH receptors by gp120.

Influencia de la infección por VIH/sida sobre algunos indicadores bioquímicos del estado nutricional

“…Otros investigadores demostraron que, en respuesta a la administración exógena de la hormona del crecimiento (GH) recombinante, su acción sobre la síntesis de la albúmina disminuye con la severidad de la enfermedad (12). Por otra parte, en los individuos infectados por el VIH existe una deficiencia de la GH, puesto que la gp 120 del virus provoca un bloqueo endógeno del receptor del factor liberador de dicha hormona (13). De tal manera que la disminución en los niveles de la GH, conjunta-mente con su disminuida acción anabólica sobre la albúmina, puede influir determinantemente en la reducción de dicha proteína sérica en individuos infectados por el VIH.…”

Mathematical Model of the Effect of Affinity Hemodialysis on the T-Cell Depletion Leading to AIDS

“…AIDS is often associated with growth retardation in children and wasting in adults, the physiological mechanisms of which are presently unknown [15]. The course of illness in children differs from that in the adult and strongly tends toward developmental retardation and failure of somatic growth.…”

“…The effect is correlated with gp120 effects on growth hormone release. gp120 acts at both the hypothalamus and pituitary to suppress GH release when injected at doses of 400 ng into the brain of the rat [15].…”

“…The envelope protein gp120 appears to play a role in AIDS dementia. Dissociated gp120 can be found in significant concentrations in the parenchyma and cerebrospinal fluid of brains in infected individuals, even in the earliest stages of HIV-1 disease [15]. gp120 has been found to cause death of neurons at low concentrations by indirect mechanisms [25,26] and to result in direct damage to neuronal cells [16][17][18].…”

“…These homologies have significant clinical correlates in HIV and AIDS. gp120 appears to play a role in AIDS dementia and can be found in significant concentrations in the cerebrospinal fluid even in the earliest stages of disease [15]. Dissociated gp120 is known to kill neurons at concentrations of F10 ng/ml [16][17][18].…”