RESUMO
Arginine vasopressin (AVP) is produced in the paraventricular (PVN) and supraoptic nuclei (SON). Peripheral AVP, which is secreted from the posterior pituitary, is produced in the magnocellular division of the PVN (mPVN) and SON. In addition, AVP is produced in the parvocellular division of the PVN (pPVN), where corticotrophin-releasing factor (CRF) is synthesized. These peptides synergistically modulate the hypothalamic-pituitary-adrenal (HPA) axis. Previous studies have revealed that the HPA axis was activated by hypovolemia. However, the detailed dynamics of AVP in the pPVN under hypovolemic state has not been elucidated. Here, we evaluated the effects of hypovolemia and hyperosmolality on the hypothalamus, using AVP-enhanced green fluorescent protein (eGFP) transgenic rats. Polyethylene glycol (PEG) or 3% hypertonic saline (HTN) was intraperitoneally administered to develop hypovolemia or hyperosmolality. AVP-eGFP intensity was robustly upregulated at 3 and 6 h after intraperitoneal administration of PEG or HTN in the mPVN. While in the pPVN, eGFP intensity was significantly increased at 6 h after intraperitoneal administration of PEG with significant induction of Fos-immunoreactive (-ir) neurons. Consistently, eGFP mRNA, AVP hnRNA, and CRF mRNA in the pPVN and plasma AVP and corticosterone were significantly increased at 6 h after intraperitoneal administration of PEG. The results suggest that AVP and CRF syntheses in the pPVN were activated by hypovolemia, resulting in the activation of the HPA axis.
Assuntos
Arginina Vasopressina/genética , Proteínas de Fluorescência Verde/genética , Sistema Hipotálamo-Hipofisário/metabolismo , Hipovolemia/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Animais , Corticosterona/sangue , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Modelos Animais de Doenças , Genes Reporter , Proteínas de Fluorescência Verde/biossíntese , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hipovolemia/genética , Hipovolemia/fisiopatologia , Injeções Intraperitoneais , Masculino , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Polietilenoglicóis/administração & dosagem , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Transgênicos , Ratos Wistar , Solução Salina Hipertônica/administração & dosagem , Núcleo Supraóptico/metabolismo , Núcleo Supraóptico/fisiopatologia , Fatores de Tempo , Regulação para CimaRESUMO
The mechanism of onset of hypoglycemia in patients with carnitine deficiency has yet to be determined. Using mice with systemic carnitine deficiency (JVS mice), we examined this mechanism, focusing on the weaning period (days 14-28 postpartum). For normal mice, the survival rate was 100%, and no hypoglycemia was observed at all. Gastric lactose began to decrease on day 17, and cellulose increased sharply in amount thereafter. For JVS mice, the survival rate was 77% on day 14 and 28% on day 28. From day 21 on, hypoglycemia was noted. Gastric lactose had disappeared almost completely by day 17, and cellulose was almost undetectable from days 14 to 28. Expression of orexin mRNA in the hypothalamus did not differ between JVS and normal mice on day 14, but was suppressed in JVS mice on days 21 and 28. When JVS mice were fed a carnitine-rich diet, suppression of expression of orexin mRNA in hypothalamus was eliminated, and on day 28 lactose and cellulose were detected in the stomach without hypoglycemia. In conclusion, the suppression of the expression of orexin in the hypothalamus during the weaning period may be involved in the marked anorexia in JVS mice, which eventually leads to death from hypoglycemia.
Assuntos
Glicemia/metabolismo , Carnitina/sangue , Carnitina/deficiência , Hipoglicemia/sangue , Hipotálamo/metabolismo , Neuropeptídeos/biossíntese , Ácido 3-Hidroxibutírico/sangue , Animais , Comportamento Animal/fisiologia , Carnitina/administração & dosagem , Celulose/administração & dosagem , Escuridão , Feminino , Hipoglicemia/genética , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lactose/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Neuropeptídeo Y/biossíntese , Neuropeptídeo Y/genética , Neuropeptídeos/antagonistas & inibidores , Neuropeptídeos/genética , Hibridização de Ácido Nucleico , Orexinas , Gravidez , Pró-Opiomelanocortina/biossíntese , Pró-Opiomelanocortina/genética , Organismos Livres de Patógenos EspecíficosRESUMO
Ghrelin is a potent, centrally acting orexigenic hormone. Recently, we showed that centrally administered ghrelin is a potent antidipsogenic hormone in 24-h water deprived rats. In this study, we examined the effect of intracerebroventricular (icv) injection of ghrelin on angiotensin II (AII)-induced water intake in rats. We also examined the effects of icv injection of ghrelin on drinking induced by intraperitoneal injection of an isotonic polyethylene glycol (PEG) solution that causes isotonic hypovolemia. Water intake induced by the icv injection of AII or ip injection of PEG was significantly reduced after icv injection of ghrelin, although food intake was stimulated by the hormone. The drinking induced by AII was also inhibited by the icv administration of 4alpha-phorbol 12, 13-didecanoate, an agonist of the osmosensitive TRPV4 channel. This study showed that ghrelin is a potent antidipsogenic peptide by antagonizing general dipsogenic mechanisms including those activated by AII and hypovolemia in rats.