Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Canada.
Reproduction. 2020 Sep;160(3):445-454. doi: 10.1530/REP-20-0068.
Nesfatin-1 is a naturally occurring orphan ligand in fish and mammals. Research in our lab resulted in the identification of an inhibitory role for nesfatin-1 on pituitary hormones (goldfish) and oocyte maturation (zebrafish). The present study is an extension of these original findings and aimed to determine whether nesfatin-1 has any additional effects on HPG genes in male and female goldfish. We found that a single i.p. injection of synthetic nesfatin-1 (50 ng/g body weight) downregulated the expression of salmon gonadotropin-releasing hormone (sgnrh), chicken gnrh-II (cgnrh-II), kisspeptin receptor (gpr54a) and brain aromatase (cyp19a1b) mRNAs in the hypothalamus of both male and female goldfish at 15 min post-administration. In the pituitary of both males and females, nesfatin-1 reduced luteinizing hormone beta (lhβ) and follicle stimulating hormone beta (fshβ) mRNA expression at 60 min and gpr54a mRNA at 15 min. Similarly, the gonadotropin receptors lhr and fshr were downregulated in the gonads. Meanwhile, gonadotropin inhibiting hormone (gnih), gnih receptor, kisspeptin 1 (kiss1) and gpr54a mRNA expression in the gonads were increased post-nesfatin-1 treatment. Nesfatin-1 negatively influences the star, cytochrome P450 family 11 subfamily A member 1, anti-mullerian hormone and aromatase mRNAs. In agreement with these results, nesfatin-1 reduced plasma estradiol and testosterone in female and male goldfish circulation at 60 min post-injection. The information generated through this research further solidified nesfatin-1 as an inhibitor of reproductive hormones in fish. Targeting nesfatin-1 and related peptides could yield beneficial effects in fish reproduction and aquaculture.
内脂素-1 是鱼类和哺乳动物中天然存在的孤儿配体。我们实验室的研究结果表明，内脂素-1 对垂体激素（金鱼）和卵母细胞成熟（斑马鱼）具有抑制作用。本研究是对这些原始发现的扩展，旨在确定内脂素-1 是否对雄性和雌性金鱼的 HPG 基因有任何其他影响。我们发现，单次腹腔注射合成内脂素-1（50ng/g 体重）可在给药后 15 分钟下调雄性和雌性金鱼下丘脑的促性腺激素释放激素（sgnrh）、鸡促性腺激素释放激素-II（cgnrh-II）、 kisspeptin 受体（gpr54a）和脑芳香酶（cyp19a1b）mRNA 的表达。在雄性和雌性金鱼的垂体中，内脂素-1 在 60 分钟时降低黄体生成素β（lhβ）和卵泡刺激素β（fshβ）mRNA 的表达，在 15 分钟时降低 gpr54a mRNA 的表达。同样，在性腺中，促性腺激素受体 lhr 和 fshr 也被下调。与此同时，在性腺中，促性腺激素抑制激素（gnih）、gnih 受体、 kisspeptin1（kiss1）和 gpr54a mRNA 的表达增加。内脂素-1 负调控星、细胞色素 P450 家族 11 亚家族 A 成员 1、抗缪勒管激素和芳香酶 mRNA。与这些结果一致，内脂素-1 在注射后 60 分钟降低了雌性和雄性金鱼循环中的雌二醇和睾酮。通过这项研究获得的信息进一步证实了内脂素-1 是鱼类生殖激素的抑制剂。靶向内脂素-1 和相关肽可能对鱼类繁殖和水产养殖产生有益影响。
