Centrally Administered Murine-Leptin Stimulates the Hypothalamus-Pituitary- Adrenal Axis through Arginine-Vasopressin

Autor: Shigeki Yamamoto, Keiko Kai, Takashi Fujihira, Sumiya Eto, Emiko Morita, Isao Morimoto
Rok vydání: 2000
Předmět:
Leptin
Male
Hypothalamo-Hypophyseal System
endocrine system
medicine.medical_specialty
Vasopressin
Pro-Opiomelanocortin
medicine.drug_class
Endocrinology
Diabetes and Metabolism

Pituitary-Adrenal System
Adrenocorticotropic hormone
Cellular and Molecular Neuroscience
Corticotropin-releasing hormone
chemistry.chemical_compound
Endocrinology
Adrenocorticotropic Hormone
Proopiomelanocortin
Corticosterone
Internal medicine
medicine
Animals
RNA
Messenger

Rats
Wistar

Injections
Intraventricular

biology
Endocrine and Autonomic Systems
Chemistry
digestive
oral
and skin physiology

Blotting
Northern

Receptor antagonist
Stimulation
Chemical

Rats
Arginine Vasopressin
nervous system
Hypothalamus
biology.protein
DNA Probes
Antidiuretic Hormone Receptor Antagonists
hormones
hormone substitutes
and hormone antagonists
Zdroj: Neuroendocrinology. 71:366-374
ISSN: 1423-0194
0028-3835
Popis: Starvation induces a decrease in circulating leptin levels and activation of the hypothalamus-pituitary-adrenal (HPA) axis. Leptin inhibits the HPA axis in unfed rodents or genetically leptin-deficient ob/ob mice, whereas it stimulates corticotropin-releasing hormone (CRH) gene expression in the paraventricular nucleus (PVN). However, the interactions between leptin, CRH and the HPA axis are poorly understood and are likely to be complex. We recently demonstrated that central leptin administration caused increases in plasma arginine-vasopressin (AVP) and AVP gene expression of the PVN in nonstressful rats. AVP stimulates the release of adrenocorticotropic hormone (ACTH), but it also potentiates the action of CRH on ACTH release. In this study, we investigated the effects of leptin on plasma ACTH and corticosterone levels, CRH mRNA of the PVN and proopiomelanocortin (POMC) mRNA of the pituitary in nonstrained rats. Intracerebroventricularly administered leptin caused increases in plasma ACTH and corticosterone levels in dose-dependent manners. In Northern blot analyses, the leptin injection induced significant increases in the expression of CRH mRNA in the PVN and POMC mRNA in the pituitary. The increased plasma ACTH and corticosterone levels by leptin were attenuated with intracerebroventricular pretreatment of a V1a receptor antagonist (OPC-21268) or a V1a/V1b receptor antagonist (dP[Tyr(Me)2]AVP), but not with that of a V2 receptor antagonist (OPC-31260). The leptin-induced CRH mRNA expression in the PVN and POMC mRNA expression in the pituitary were also reduced by the pretreatment with OPC-21268 and dP[Tyr(Me)2]AVP. These results suggest that intracerebroventricular leptin administration activates the HPA axis by AVP receptor activation through V1a receptors in the PVN which in turn activates CRH neurons to drive ACTH and corticosterone secretion in concert with AVP in nonstrained rats.
Databáze: OpenAIRE