INVESTIGADORES
GIOVAMBATTISTA Andres
artículos
Título:
Sexual dimorphism in the hypothalamo-pituitary-adrenal (HPA) axis and TNFalpha responses to phospholipase A2-related neurotoxin (from crotalus durissus terrifcus) challenge.
Autor/es:
CHISARI, A; GAILLARD, R; GIOVAMBATTISTA A; VOIROL MJ; PIERMARÍA, JUDITH; SPINEDI, E
Revista:
J Endocrinol Invest
Editorial:
New York
Referencias:
Año: 2000 p. 440 - 448
ISSN:
0391-4097
Resumen:
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