Effect of relaxin-3 on Kiss-1, gonadotropin-releasing hormone, and gonadotropin subunit gene expression

Reprod Med Biol. 2019 Sep 5;18(4):397-404. doi: 10.1002/rmb2.12298. eCollection 2019 Oct.

Abstract

Purpose: Relaxin-3 is a hypothalamic neuropeptide that belongs to the insulin superfamily. We examined whether relaxin-3 could affect hypothalamic Kiss-1, gonadotropin-releasing hormone (GnRH), and pituitary gonadotropin subunit gene expression.

Methods: Mouse hypothalamic cell models, mHypoA-50 (originated from the hypothalamic anteroventral periventricular region), mHypoA-55 (originated from arcuate nucleus), and GT1-7, and the mouse pituitary gonadotroph LβT2 were used. Expression of Kiss-1, GnRH, and luteinizing hormone (LH)/follicle-stimulating hormone (FSH) β-subunits was determined after stimulation with relaxin-3.

Results: RXFP3, a principle relaxin-3 receptor, was expressed in these cell models. In mHypoA-50 cells, relaxin-3 did not exert a significant effect on Kiss-1 expression. In contrast, the Kiss-1 gene in mHypoA-55 was significantly increased by 1 nmol/L relaxin-3. These cells also express GnRH mRNA, and its expression was significantly stimulated by relaxin-3. In GT1-7 cells, relaxin-3 significantly upregulated Kiss-1 expression; however, GnRH mRNA expression in GT1-7 cells was not altered. In primary cultures of fetal rat neuronal cells, 100 nmol/L relaxin-3 significantly increased GnRH expression. In pituitary gonadotroph LβT2, both LHβ- and FSHβ-subunit were significantly increased by 1 nmol/L relaxin-3.

Conclusions: Our findings suggest that relaxin-3 exerts its effect by modulating the expression of Kiss-1, GnRH, and gonadotropin subunits, all of which are part of the hypothalamic-pituitary-gonadal axis.

Keywords: gonadotropin; gonadotropin‐releasing hormone; hypothalamic‐pituitary‐gonadal axis; kisspeptin; relaxin‐3.