Suppressive action of nesfatin-1 and nesfatin-1-like peptide on cortisol synthesis in adrenal cortex cells

Abstract

AbstractNucleobindin-derived peptides, nesfatin-1 [NESF-1] and nesfatin-1-like-peptide [NLP] have diverse roles in endocrine and metabolic regulation. While both peptides showed a stimulatory effect on the synthesis of POMC, the ACTH precursor in mouse corticotrophs, whether NESF-1 and NLP have any direct effect on glucocorticoid [GC] synthesis in the adrenal cortex remains unknown. The main aim of this study was to determine if NESF-1 and/or NLP act directly on adrenal cortex cells to regulate cortisol synthesisin vitro. Whether NLP injection affects stress-hormone gene expression in the adrenal gland and pituitaryin vivoin mice was also assessed. In addition, cortisol synthetic pathway inNucb1knockout [KO] mice was studied. Human adrenal cortical [H295R] cells showed immunoreactivity for both NUCB1/NLP and NUCB2/NESF-1 using immunohistochemistry. NLP and NESF-1 decreased the expression of steroidogenic enzymes, cortisol synthesis and release through the AC/PKA/CREB pathway in H295R cells. Similarly, intraperitoneal injection of NLP in mice decreased the expression of enzymes involved in GC synthesis in the adrenal gland while increasing the expression ofPomc,Pcsk1andCrhr1in the pituitary. Moreover, theMc2rmRNA level was enhanced in the adrenal gland samples of NLP injected mice. However, the global genetic disruption inNucb1did not affect most steroidogenic enzyme mRNAs, andPomc,Pcsk2andCrhr1mRNAs in mice adrenal gland and pituitary gland, respectively. Collectively, these data provide the first evidence that NLP and NESF-1 directly decreased cortisol synthesis and secretionin vitro.NUCB peptides still might play its stimulatory effect on GC synthesis and secretion through their positive effects on ACTH-MC2R pathway in the pituitary.