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Sexual dimorphism in the hypothalamo-pituitary-adrenal (HPA) axis and TNFalpha responses to phospholipase A2-related neurotoxin (from crotalus durissus terrifcus) challenge.
Chisari, A N; Gaillard, R C; Giovambattista, A; Piermaría, J; Spinedi, E.
Afiliação
  • Chisari AN; Neuroendocrine Unit, IMBICE, La Plata National University, Argentina.
J Endocrinol Invest ; 23(7): 440-8, 2000.
Article em En | MEDLINE | ID: mdl-11005268
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 compounds and that their main component is a specific phospholipase type 2 (PLA2). It has been recently described that the venom from crotalus durissus terrificus (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 stimulate both TNFalpha and neuroendocrine functions in a sexual dimorphic fashion. For this purpose the modulatory role of endogenous sex steroids during neurotoxemia was evaluated. Our results indicate that SV (25 microg/animal) stimulates the hypothalamo-pituitary-adrenal axis and TNFalpha secretion when administered (ip) to adult male mice, such responses were characterized by a time-related enhance in plasma glucose, ACTH, corticosterone and TNFalpha levels. SV-stimulated glycemia, corticosteronemia and adrenal glucocorticoid 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 plasma 30 min post-SV. Estradiol (E2) treatment, in gonadectomized mice, abolished some characteristics of the sexual dimorphism, such as hyperglycemia, hypercorticosteronemia and hypercytokinemia. Finally, in vitro experiments indicate that: a) gonadectomy increased spontaneous and SV-stimulated cytokine output by incubated peripheral mononuclear cells (PMNC), regardless of the sex; and b) despite E2 treatment, in gonadectomized, did not modify the pattern of basal and SV-elicited TNFalpha secretion induced by orchidectomy, fully reversed the enhance in basal and SV-stimulated cytokine release found after ovariectomy alone. Our results further indicate that neurotoxemia, due to SV challenge, induces several symptoms common to those of inflammatory stress; they also strongly support that both gender and endogenous sex steroids are responsible for neuroendocrine-immunological sexual dimorphism.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipases A / Caracteres Sexuais / Fator de Necrose Tumoral alfa / Glândulas Suprarrenais / Venenos de Crotalídeos / Sistema Hipotálamo-Hipofisário Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Endocrinol Invest Ano de publicação: 2000 Tipo de documento: Article País de afiliação: Argentina País de publicação: Itália
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipases A / Caracteres Sexuais / Fator de Necrose Tumoral alfa / Glândulas Suprarrenais / Venenos de Crotalídeos / Sistema Hipotálamo-Hipofisário Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Endocrinol Invest Ano de publicação: 2000 Tipo de documento: Article País de afiliação: Argentina País de publicação: Itália