| First Author | Hatef A | Year | 2017 |
| Journal | Biol Reprod | Volume | 96 |
| Issue | 3 | Pages | 635-651 |
| PubMed ID | 28339602 | Mgi Jnum | J:243975 |
| Mgi Id | MGI:5912754 | Doi | 10.1095/biolreprod.116.146621 |
| Citation | Hatef A, et al. (2017) Gonadotropin-releasing hormone, kisspeptin, and gonadal steroids directly modulate nucleobindin-2/nesfatin-1 in murine hypothalamic gonadotropin-releasing hormone neurons and gonadotropes. Biol Reprod 96(3):635-651 |
| abstractText | Neuroendocrine regulation of metabolism and reproduction are tightly interlinked. Nesfatin-1 is an 82 amino acid metabolic peptide derived from nucleobindin-2 (NUCB2). NUCB2 mRNA and protein significantly increase in the hypothalamus of rats during puberty-to-adult transition. Administration of nesfatin-1 modulates circulating LH and testosterone in male rats. However, whether nesfatin-1 acts directly on neurons and gonadotropes remain unknown. In addition, whether reproductive hormones of the hypothalamo-pituitary gonadal axis modulate NUCB2/nesfatin-1 is unclear. To address these, we employed murine hypothalamic (GT1-7) and pituitary (LbetaT2) cells in vitro. Nucb2 expression, and NUCB2/nesfatin-1 immunoreactivity were observed in both GT1-7 and LbetaT2 cells, and in the hypothalamus of mice. Nesfatin-1 co-localized GnRH in GT1-7 cells, and in the hypothalamic perikarya of mice. Cells were treated with kisspeptin, GnRH, and estradiol and testosterone, as well as nesfatin-1 for 2, 6 or 24 hours. Synthetic nesfatin-1 increased Kiss1r and Gnrh expression in GT1-7 cells and Lhbeta in LbetaT2. Nesfatin-1 increased GnRH and LHbeta protein expression in GT1-7 and LbetaT2 at 6-hour post incubation respectively. Both NUCB2 mRNA and protein were increased in GT1-7 cells treated with kisspeptin. Testosterone increased NUCB2 mRNA and protein expression in GT1-7 and LbetaT2. 17beta-estradiol increased NUCB2 mRNA and protein expression in LbetaT2. Nesfatin-1 acts directly on hypothalamic neurons and gonadotropes to elicit a generally positive influence on the endocrine milieu regulating reproduction in mice. Reproductive hormones, in turn, modulate brain and pituitary NUCB2/nesfatin-1. In conclusion, we provide additional information to designate nesfatin-1 as a novel, additional factor that helps reproductive success. |
