No abstract

To clarify the role of ghrelin in the regulatory mechanism of energy metabolism, we analyzed the effects of centrally and peripherally administered ghrelin on noradrenaline release in the brown adipose tissue (BAT) of rats using a microdialysis system. I.c.v. administration of ghrelin at a dose of 500 pmol suppressed noradrenaline release in BAT, and microinjection of ghrelin (50 pmol) into the paraventricular nucleus (PVN) or arcuate nucleus (ARC) of the hypothalamus also suppressed noradrenaline release in BAT. In addition, i.v. administered ghrelin (30 nmol) suppressed noradrenaline release in BAT, and this suppression was blocked by a vagotomy. Neither i.c.v. nor i.v. administration of des-acyl ghrelin, which does not bind to GH secretagogue receptor type 1a (GHS-R1a), affected noradrenaline release in BAT. These results indicate that ghrelin increases energy storage by suppressing the activity of the sympathetic nerve innervating BAT. It seems that the PVN and ARC, which express GHSR1a, are the sites of action of ghrelin in the brain and that the action of peripheral ghrelin on the sympathetic nerve activity innervating BAT is mediated by the vagal nerve, which also expresses GHS-R1a.

No abstract

We previously demonstrated that urocortin 2 (Ucn 2) is expressed in the proopiomelanocortin (POMC) cells of rat pituitary. However, the regulatory mechanism of pituitary synthesis and secretion of Ucn 2 remained to be clarified. We hypothesized that hypothalamic hormones and glucocorticoids may control the expression and secretion of pituitary Ucn 2, as Ucn 2 is expressed in POMCexpressing cells in the pituitary. Thus, in the present study, we tested this hypothesis using primary culture of rat pituitary cells.

Nemoto T, Iwasaki-Sekino A, Yamauchi N, Shibasaki T. Role of urocortin 2 secreted by the pituitary in the stress-induced suppression of luteinizing hormone secretion in rats. Am J Physiol Endocrinol Metab 299: E567-E575, 2010. First published July 27, 2010; doi:10.1152/ajpendo.00163.2010.-We have previously shown that urocortin 2 (Ucn 2), a member of the corticotropinreleasing factor (CRF) peptide family that binds to CRF type 2 receptor, is expressed in proopiomelanocortin (POMC) cells of rat pituitary and that its secretion and expression are increased by CRF in both the anterior and intermediate lobes and suppressed by glucocorticoids in the anterior lobe. We have also shown that Ucn 2 secreted by POMC cells acts on gonadotrophs expressing CRF type 2 receptors and inhibits the expression and secretion of gonadotropins. In the present study, we examined whether pituitary Ucn 2 is involved in stress-induced inhibition of gonadotropin secretion. A 90-min period of immobilization stress increased POMC mRNA expression without influencing Ucn 2 mRNA expression and suppressed luteinizing hormone (LH) ␤-subunit mRNA expression in the anterior lobe and plasma LH levels, while it increased both POMC and Ucn 2 mRNA expression in the intermediate lobe of the pituitary. Pretreatment with anti-CRF IgG blocked immobilization-induced increases in plasma ACTH and corticosterone and in POMC mRNA expression in both pituitary lobes and Ucn 2 mRNA expression in the intermediate pituitary. It also blocked immobilization-induced suppression of plasma LH and LH ␤-subunit mRNA expression. Pretreatment with anti-Ucn 2 IgG blocked immobilization-induced suppression of plasma LH and LH ␤-subunit expression without affecting immobilization-induced ACTH and corticosterone release and POMC or Ucn 2 mRNA expression. These results suggest that CRF suppresses the secretion and expression of LH probably through pituitary Ucn 2 in stress. luteinizing hormone; corticotropin-releasing factor; pituitary STRESS INHIBITS REPRODUCTIVE function (12,13,23). The hormones composing the hypothalamic-pituitary-adrenal (HPA) axis such as corticotropin-releasing factor (CRF), adrenocorticotropin (ACTH), ␤-endorphin, and corticosteroids reportedly play important roles in the suppressive influence of stress on reproductive function (41-43). CRF is a key stress mediator in the endocrine system, autonomic nervous system, emotion, and behavior (4,19,46). The various actions of CRF are mediated through two subtypes of CRF receptors (CRF-R), CRF-R1 and CRF-R2. CRF binds with a higher affinity to CRF-R1 than to CRF-R2 (4, 18). Urocortin 2 (Ucn 2) is a CRF peptide family and shows higher affinities to both CRF-R1 and CRF-R2 compared with CRF, in particular to CRF-R2 (40). Hypothalamic CRF inhibits gonadotropin-releasing hormone (GnRH) neuron activity either directly or indirectly through ␤-endorphin in the arcuate nucleus (42, 43). Intracerebroventricular infusion of CRF in the third ventricle inhibits the estrous cycle and ovulation and reduces immunoreactive GnRH s...