Nesfatin-1 suppresses fish reproductive axis and gonadal steroidogenesis

Abstract

<jats:p>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 intraperitoneal (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 minutes 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 minutes, and gpr54a mRNA at 15 minutes. 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 were in the gonads were increased post nesfatin-1 treatment. Nesfatin-1 negatively influences the steroidogenic acute regulatory protein, 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. The suppression of nesfatin-1 and related peptides could yield beneficial effects in fish reproduction and aquaculture.</jats:p>

The Role of the Gastric Hormones Ghrelin and Nesfatin-1 in Reproduction

“…In line with the observations above, 200 pmol nesfatin-1 icv injected in male rats elevated plasma testosterone [252], while icv injection with 10 µg nesfatin-1 decreased serum testosterone in prepubertal and adult rats [226]. Similarly, also ip injection of nesfatin-1-like peptide and synthetic nesfatin-1 reduced plasma testosterone in female and male goldfish [246,247]. In addition, plasma estradiol in female and male goldfish was also decreased due to ip injection of nesfatin-1-like peptide or synthetic nesfatin-1 [246,247].…”

“…In vivo, ip injection of nesfatin-1-like peptide reduced mRNA expression in the ovary of FSH receptor, gonadotropin-inhibiting hormone and its receptor and kisspeptin in goldfish [246]. Similarly, synthetic nesfatin-1 reduced ovarian mRNA expression of the LH and FSH receptors in goldfish after ip injection; however, in contrast to nesfatin-1-like peptide, synthetic nesfatin-1 increased ovarian mRNA expression of gonadotropin inhibiting hormone, its receptor as well as kisspeptin 1 and its receptor in goldfish [247]. In granulosa cells, nesfatin-1 in vitro increased progesterone secretion as well as cell proliferation via modification of nitric oxide production and non-enzyme scavenging activity [236].…”

“…Similarly, ip injected nesfatin-1-like peptide reduced mRNA expression in the pituitary of LHβ, FSHβ, kisspeptin and its receptor, while increasing mRNA expression of gonadotropin-inhibiting hormone and of its receptor in male and female goldfish [246]. Additionally, ip injection of synthetic nesfatin-1 reduced mRNA expression of pituitary LHβ and FSHβ within 60 min and kisspeptin receptor within 15 min in male and female goldfish [247]. The effects of nesfatin-1-induced suppression of LH expression, e.g., on estrous cycle, sexual maturation, fertility etc., should be investigated in the future.…”

“…Similarly, also ip injection of nesfatin-1-like peptide and synthetic nesfatin-1 reduced plasma testosterone in female and male goldfish [246,247]. In addition, plasma estradiol in female and male goldfish was also decreased due to ip injection of nesfatin-1-like peptide or synthetic nesfatin-1 [246,247]. In the present literature, two studies report an increased circulating level of nesfatin-1 peptide in patients suffering from PCOS compared to controls [245,253], with strong positive correlations between nesfatin-1 and BMI and HOMA-IR [245,253].…”

“…Furthermore, nesfatin-1-like peptide and synthetic nesfatin-1 affected gonadal expression activity, e.g., ip injection of nesfatin-1-like peptide into goldfish reduced mRNA expression in the testis of LH and FSH receptor, gonadotropin-inhibiting hormone and its receptor as well as kisspeptin [246]. Moreover, synthetic nesfatin-1 reduced LH and FHS receptor mRNA and increased gonadotropin-inhibiting hormone, gonadotropin-inhibiting hormone receptor, kisspeptin 1 and kisspeptin receptor gonadal mRNA in male goldfish [247].…”