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

Abstract

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 V_1a receptor antagonist (OPC-21268) or a V_1a/V_1b 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 V_1a receptors in the PVN which in turn activates CRH neurons to drive ACTH and corticosterone secretion in concert with AVP in nonstrained rats.

Leptin downregulates heat shock protein-70 (HSP-70) gene expression in chicken liver and hypothalamus

“…This result corroborates previous data in birds (Yahav et al 1997;Leandro et al 2004;Mahmoud et al 2004) and in mammals (Morimoto et al 2000;Huang et al 2001). Levels of HSP-70 mRNA do not differ between tissues within the same gender; however, they are higher in male compared with female chickens.…”

“…Leptin, the adipocyte-derived hormone and the key regulator of food intake and energy homeostasis (Zhang et al 1994), has been shown to modulate HPA axis activity (Morimoto et al 2000), SNS activity (Haynes et al 1997), and the release of proinflammatory cytokines (Lappas et al 2005), implying that it has the potential to modify the stress response. Emerging evidence suggests that leptin modulates key processes involved in oxidative stress in mammals (Bouloumie et al 1999).…”

Neural Substrates Underlying Interactions between Appetite Stress and Reward

“…In contrast to data showing an inhibitory effect of leptin on the stress response, lean humans generally show a reduced a HPA axis activation to various stressors compared to overweight individuals (who are likely to have higher plasma leptin levels than lean subjects). The mouse HPA axis is activated by leptin (increasing hypothalamic CRH and pituitary POMC mRNA and increasing circulating ACTH and corticosterone), though this effect is mediated by vasopressin acting via central V1a/b receptors [54] and thus may represent an alternative pathway that is perhaps more relevant to chronic stress. …”

Long-day photoperiod interacts with vasopressin and food restriction to modulate reproductive status, and vasopressin receptor expression of male Golden spiny mice

“…In rats intracerebroventricular administration of leptin significantly increased vasopressin mRNA expression in the supraoptic nucleus of the hypothalamus (Yamamoto et al, 1999). In another study central administration of leptin to rats, has been shown to activate Avpr1a in the paraventricular nucleus of the hypothalamus to regulate neuroendocrine axes such as the hypothalamus-pituitary-adrenal axis (Morimoto et al, 2000). Accordingly, the significant increase in Avpr1a mRNA expression in the present study, particularly in the hypothalamus of FR mice is likely to be induced by the repeated leptin injections throughout the acclimation period.…”