Nesfatin-1 stimulates the hypothalamus-pituitary-interrenal axis hormones in goldfish

Abstract

Stress in vertebrates is mediated by the hypothalamus-pituitary-adrenal [in mammals]/interrenal [ in fish] (HPA/I) axis, which produces the corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH) and corticosteroids, respectively. Nesfatin-1, a novel anorexigenic peptide encoded in the precursor nucleobindin-2 (NUCB2), is increasingly acknowledged as a peptide that influences the stress axis in mammals. The primary aim of this study was to characterize the putative effects of nesfatin-1 on the fish HPI axis, using goldfish (Carassius auratus) as an animal model. Our results demonstrated that nucb2/nesfatin-1 transcript abundance was detected in the HPI tissues of goldfish, with most abundant expression in the pituitary. NUCB2/nesfatin-1-like immunoreactivity was found in the goldfish hypothalamus, pituitary and interrenal cells of the head kidney. GPCR12, a putative receptor for nesfatin-1 was also detected in the pituitary and interrenal cells. NUCB2/nesfatin-1-like immunoreactivity was observed in ACTH-expressing pituitary corticotrophs. Acute netting and restraint stress upregulated nucb2/nesfatin-1 mRNA levels in the forebrain, hypothalamus and pituitary, as well as crf and crf-r1 expression in the forebrain and hypothalamus. Intraperitoneal and intracerebroventricular administration of nesfatin-1 increased cortisol release and hypothalamic crf mRNA levels, respectively. Finally, we found that nesfatin-1 significantly stimulated ACTH secretion from dispersed pituitary cells in vitro. Collectively, our data provide the first evidence showing that nesfatin-1 is a stress responsive peptide, which modulates the stress axis hormones in fish.

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

“…Previous studies from our lab also showed that NESF-1 is a stress-responsive peptide that stimulates stress-related hypothalamus-pituitary-interrenal [HPI; similar to mammalian HPA tissues] axis hormones in goldfish 2 . Moreover, NESF-1 was shown to directly stimulate the synthesis of ACTH precursor in mouse pituitary corticotrophs 1 .…”

“…Given that NUCBs are DNA binding proteins 1 , the staining found in the nucleus is reflective of that role. NUCB1/NLP-like immunoreactivity was reported in the central nervous system and peripheral tissues, including endocrine cells of the anterior pituitary of rats and mice 1 , 28 , mouse insulinoma MIN6 cell line and mouse pancreatic beta cells 17 as well as testis, ovary, and head kidney interrenal cells 2 and pituitary of goldfish 18 . The results reported here show that human adrenal cortex cells express NUCB peptides and possibly other bioactive peptides residing within it, which may act directly on these cells to regulate the steroidogenesis pathway and cortisol synthesis.…”

“…In recent years, nesfatin-1 [NESF-1; processed from nucleobindin-2/NUCB2] has received much attention due to its roles in metabolism, stress, and anxiety. NESF-1 and nesfatin-1-like-peptide (NLP) affect synthesis of stress hormones 1 , 2 . The release of glucocorticoids [GC] as end products in the stress/HPA axis modulates metabolism, potentially impacting energy availability through catabolic processes.…”

Tissue-Specific Modulation of Gluco- and Growth-Regulatory Factor Abundance by Nesfatin-1 and Nesfatin-1-like Peptide in Goldfish

“…Nesfatin-1 and Nlp are key players in the regulation of growth [3,15], feeding [1,2,7,16], reproduction [4,5,8], heart function [6,17], and hormone secretion [3][4][5][8][9][10]15,18] in fish and mammals. Overall, nesfatin-1 and Nlp are multifunctional peptides with tissue-specific, hormone-like actions in fish and mammals.…”

“…These results suggest a general suppressive effect for nesfatin-1 on Gh-Igf axis in goldfish. Meanwhile, nesfatin-1 stimulated both pituitary adrenocorticotrophic hormone (Acth) and cortisol in vivo in goldfish [9]. The suppressive role of nesfatin-1 on serum luteinizing hormone (Lh) and Lh beta and follicle-stimulating hormone (Fsh) beta mRNA was also reported in goldfish [5].…”