Sexual dimorphism in the hypothalamo-pituitary-adrenal (HPA) axis and TNF alpha responses to phospholipase A(2)-related neurotoxin (from crotalus durissus terrificus) challenge

Neuroendocrine-immune interactions are vital for the individual's survival in certain physiopathological conditions such as sepsis and tissular injury . It is known that several snake venoms (SV) are potent neurotoxic compound s and that their main component is a specific phospholipase type 2 (PLA(2)) . It has been recently described that the venom from crotalus durissus terr ificus (SV) possesses a cytotoxic effect in different in vitro and in vivo animal models. In the present study we investigated whether SV is able to s timulate both TNF alpha and neuroendocrine functions in a sexual dimorphic fashion. For this purpose the modulatory role of endogenous sex steroids du ring neurotoxemia was evaluated. Our results indicate that SV (25 mu g/anim al) stimulates the hypothalamo-pituitary-adrenal axis and TNF alpha secreti on when administered (ip) to adult male mice, such responses were character ized by a time-related enhance in plasma glucose, ACTH, corticosterone and TNF alpha levels. SV-stimulated glycemia, corticosteronemia and adrenal glu cocorticoid were sexually dimorphic. Twenty-day gonadectomized mice showed a similar sexual dimorphism to that found in intact animals, however, they additionally showed a sexual dimorphic pattern in cytokine release in plasm a 30 min post-SV. Estradiol (E-2) treatment, in gonadectomized mice, abolis hed some characteristics of the sexual dimorphism, such as hyperglycemia, h ypercorticosteronemia and hypercytokinemia. Finally, in vitro experiments i ndicate that: a) gonadectomy increased spontaneous and SV-stimulated cytoki ne output by incubated peripheral mononuclear cells (PMNC), regardless of t he sex; and b) despite E-2 treatment, in gonadectomized, did not modify the pattern of basal and SV-elicited TNF alpha secretion induced by orchidecto my, fully reversed the enhance in basal and SV-stimulated cytokine release found after ovariectomy alone. Our results further indicate that neurotoxem ia, due to SV challenge, induces several symptoms common to those of inflam matory stress; they also strongly support that both gender and endogenous s ex steroids are responsible for neuroendocrine-immunological sexual dimorph ism. (C) 2000, Editrice Kurtis.