Nesfatin-1/NUCB2 may participate in the activation of the hypothalamic-pituitary-adrenal axis in rats.
Nesfatin-1 is an anorexigenic peptide originating from nucleobinding-2 (NUCB2) protein. Nesfatin-1/NUCB2-immunoreactive neurons are present in the hypothalamic paraventricular nucleus, the center of the stress-axis, and in the medullary A1 and A2 catecholamine cell groups. The A1 and A2 cell groups mediate viscerosensory stress information toward the hypothalamic paraventricular nucleus. They contain noradrenaline, but subsets of these neurons also express prolactin-releasing peptide acting synergistically with noradrenaline in the activation of the hypothalamic paraventricular nucleus during stress. We investigated the possible role of nesfatin-1/NUCB2 in the stress response. Intracerebro-ventricular administration of nesfatin-1 elevated both plasma adrenocorticotropin and corticosterone levels, while in vitro stimulation of the hypophysis was ineffective. Single, long-duration restraint stress activated (Fos positivity) many of the nesfatin-1/NUCB2-immunoreactive neurons in the parvocellular part of the hypothalamic paraventricular nucleus, evoked nesfatin-1/NUCB2 mRNA expression in the parvocellular part of the paraventricular nucleus and in the A1, but not in the A2 cell group. Nesfatin-1/NUCB2 was shown to co-localize in a high percentage of prolactin-releasing peptide producing neurons, in both medullary catecholamine cell groups further supporting its involvement in the stress response. Finally, bilateral adrenalectomy evoked an increasing nesfatin-1/NUCB2 mRNA expression, indicating that it is under the negative feedback of adrenal steroids. These data provide the first evidence for possible participation of nesfatin-1/NUCB2 in the stress-axis regulation, both at the level of the brainstem and in the hypothalamus.
Könczöl
Katalin
K
Neuromorphological and Neuroendocrine Research Laboratory, Semmelweis University, Hungarian Academy of Sciences, Budapest, Hungary.
Bodnár
Ibolya
I
Zelena
Dóra
D
Pintér
Ottó
O
Papp
Rege Sugárka
RS
Palkovits
Miklós
M
Nagy
György M
GM
Tóth
Zsuzsanna E
ZE
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D000080866:Nucleobindins; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D056690:Prolactin-Releasing Hormone / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D056690:Prolactin-Releasing Hormone; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D014446:Tyrosine 3-Monooxygenase; D003345:Corticosterone