RESUMO
In adult rats, bacterial endotoxin (lipopolysaccharide or LPS) is known to diminish the activity of the reproductive axis, mainly by inhibiting luteinizing hormone-releasing hormone (LHRH) secretion; until now, this effect has not been studied in immature rats. The aim of the present study was to evaluate the effect of LPS 1) on LHRH output (and associated changes in the release of inhibitory amino acid neurotransmitters such as gamma-aminobutyric acid (GABA) and taurine) by superfused hypothalamic fragments, and 2) on gonadotropin secretion by incubated hemipituitaries, obtained from young adult (60-day-old) and peripubertal (30-day-old) intact male rats. In adult animals, LPS induced a significant inhibition (50% of basal values) of LHRH release, accompanied by an increase in GABA and taurine output. In juvenile rats the inhibition of LHRH secretion by LPS attained 90% of basal values (p<0.0001 versus adult rats), and the concurrent increase in GABA release was significantly greater (p<0.0001 versus adult rats). LPS did not affect in vitro gonadotropin secretion in adult animals. Conversely, the release of these hormones was significantly (p<0.001 and <0.02 for LH and FSH, respectively) reduced in 30-day-old rats. Our results demonstrate the existence of age-related differences in the effect of LPS on LHRH and gonadotropin secretion. These differences might well be attributed to an increased activity of the hypothalamic GABAergic system. Furthermore, the participation of other factors known to play a role in immune-neuroendocrine relationships (e.g., corticotropin-releasing hormone, testosterone) is discussed.
Assuntos
Envelhecimento/fisiologia , Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Lipopolissacarídeos/farmacologia , Hormônio Luteinizante/metabolismo , Hipófise/metabolismo , Taurina/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Hipotálamo/efeitos dos fármacos , Hipotálamo/crescimento & desenvolvimento , Masculino , Neurotransmissores/metabolismo , Técnicas de Cultura de Órgãos , Especificidade de Órgãos , Hipófise/efeitos dos fármacos , Hipófise/crescimento & desenvolvimento , Cloreto de Potássio/farmacologia , Ratos , Ratos Wistar , Salmonella typhiRESUMO
Immune system activation is often accompanied by alterations in the reproductive axis. Interleukin-1 (IL-1), a polypeptide cytokine, has been postulated as a chemical messenger between the immune and the neuroendocrine systems. Using superfused hypothalamic fragments explanted from intact male rats, we evaluated the effects of IL-1 (0. 5 and 5 nM) on basal and N-methyl-D-aspartate (NMDA)-stimulated release of gonadotropin-releasing hormone (GnRH), and the associated modifications in the output of inhibitory amino acid neurotransmitters involved in the control of GnRH secretion. IL-1 did not modify basal GnRH release, but markedly restrained the stimulatory effect of NMDA on GnRH secretion. gamma-Aminobutyric acid, glycine and taurine concentrations significantly increased in the superfusion medium only after pretreatment with the higher dose of IL-1 (p < 0.05). Our results indicate that this cytokine inhibits NMDA- stimulated GnRH release, affecting the activity and/or the release of hypothalamic excitatory and inhibitory amino acid neurotransmitters participating in the regulation of GnRH secretion.
Assuntos
Agonistas de Aminoácidos Excitatórios/farmacologia , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo Médio/metabolismo , Interleucina-1/farmacologia , N-Metilaspartato/farmacologia , Área Pré-Óptica/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Glicina/metabolismo , Hipotálamo Médio/imunologia , Masculino , Inibição Neural/efeitos dos fármacos , Inibição Neural/imunologia , Neuroimunomodulação/efeitos dos fármacos , Neuroimunomodulação/imunologia , Área Pré-Óptica/imunologia , Ratos , Ratos Wistar , Taurina/metabolismoRESUMO
Interleukin-1 (IL-1), a polypeptide cytokine, has been postulated as a chemical messenger between the immune and the neuroendocrine system. IL-1 receptors and immunopositive neurons have been visualized in the human and rat hypothalamus, suggesting that IL-1 can act as a neurotransmitter within the brain. In the hypothalamus IL-1 and the amino acid neurotransmitters are known to modulate several functions, such as fever, anorexia and the gonadal and adrenal axis. Since the hypothalamic actions of IL-1 on the amino acid neurotransmitter output are unknown, the aim of the present paper was to evaluate the effects of IL-1 on the hypothalamic release of both, the inhibitory taurine, glycine and GABA and the excitatory glutamate, amino acid neurotransmitters. Intact adult male rats were employed. The preoptic/mediobasal hypothalamic area was dissected and superfused with Earle's balanced salt solution. Superfusate fractions were collected after a 60-min stabilization period. Following 60 min of basal release, IL-1 was added to the superfusion medium over 30 min. GABA, taurine and glycine release were significantly (p < 0.05) increased in the superfusion medium, while glutamate was not modified compared with the control group. These observations show that IL-1 increased GABA, taurine and glycine release. These effects indicate that this cytokine can affect the hypothalamic inhibitory amino acid output, which may help us to understand the mechanism by which IL-1 exerts its effects.