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[PMID]: | 29436637 | [Au] Autor: | Celichowski P; Jopek K; Milecka P; Szyszka M; Tyczewska M; Malendowicz LK; Rucinski M |
[Ad] Address: | Department of Histology and Embryology, Poznan University of Medical Sciences, 60781 Poznan, Poland. | [Ti] Title: | Nicotinamide phosphoribosyltransferase and the hypothalamic-pituitary-adrenal axis of the rat. | [So] Source: | Mol Med Rep;17(4):6163-6173, 2018 Apr. | [Is] ISSN: | 1791-3004 | [Cp] Country of publication: | Greece | [La] Language: | eng | [Ab] Abstract: | Nicotinamide phosphoribosyltransferase (Nampt), also termed visfatin, catalyses the ratelimiting step in the nicotinamide adenine dinucleotide (NAD) salvage pathway. In addition to its intracellular function (iNampt), extracellular Nampt (eNampt) also affects numerous intracellular signalling pathways. The current study investigated the role of Nampt in the regulation of the hypothalamicpituitaryadrenal (HPA) axis in rats. At 1 h after intraperitoneal administration of eNampt (4 µg/100 g) in adult male rats, serum adrenocorticotropic hormone(ACTH) and aldosterone levels remained unchanged, while corticosterone levels were notably elevated compared with the control group, as determined by ELISA. The results of reverse transcriptionquantitative polymerase chain reaction (RTqPCR) demonstrated that, in the hypothalami of eNampttreated rats, the mRNA expression levels of Fos protooncogene, which is also termed cFos, were not significantly different compared with the control group; however, the mRNA expression levels of proopiomelanocortin (POMC) were markedly increased in the pituitary gland of eNampttreated rats compared with the control group. Furthermore, in hypothalamic explants, ELISA results demonstrated that the addition of the eNampt protein exhibited no effect on corticotropinreleasing hormone (CRH) release into the incubation medium and prevented potassium ioninduced CRH release. Additionally, the eNamptinduced increase in ACTH output by pituitary gland explants was not statistically significant, compared with the control group. However, RTqPCR indicated that exposure of pituitary gland explants to eNampt and CRH increased the levels of POMC mRNA expression; the effect of eNampt, but not CRH, was inhibited by FK866, which is a specific Nampt inhibitor. In primary rat adrenocortical cell cultures, eNampt exhibited no effect on basal aldosterone or corticosterone secretion, while increases in aldosterone and corticosterone levels in response to ACTH were retained. To assess the potential role of iNampt in the regulation of adrenal steroidogenesis, experiments involving a specific Nampt inhibitor, FK866, were performed. Exposure of cultured cells to FK866 notably lowered basal aldosterone and corticosterone output compared with the control group, and completely eliminated the response of cultured cells to ACTH. The results of the present study indicated that the injected eNampt may have increased the corticosterone serum levels by acting at the pituitary level. In addition, iNampt may exert a tonic stimulating effect on the secretion of aldosterone and corticosterone from rat adrenocortical cells, as normal iNampt levels were required to retain the response of cultured rat adrenocortical cells to ACTH. Thus, these data suggest an important physiological role of both iNampt and eNampt in the regulation of the HPA axis activity in the rat. | [Pt] Publication type: | JOURNAL ARTICLE | [Em] Entry month: | 1802 | [Cu] Class update date: |
180309 | [Lr] Last revision date: | 180309 | [St] Status: | In-Process |
[do] DOI: | 10.3892/mmr.2018.8569 |
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