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

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.

Differential Regulation of Gonadotropins as Revealed by Transcriptomes of Distinct LH and FSH Cells of Fish Pituitary

“…In fish, adropin and neuropeptide W/neuropeptide B (NPWB) were associated with GH regulation [ 93 ]; however, their regulation in the HPG axis is unknown. However, relaxin-3was previously found to increase LH secretion in the rat [ 94 ], and increased lhβ and fshβ transcription in immortalized mouse gonadotrophs (LβT2 cells) [ 95 ]. In fish, relaxin-3, together with its receptor ( rxfp3 ), are expressed in the gonad and are suspected to be involved with estradiol-dependent events in follicular development [ 96 ].…”

Novel Insight into the Role of the Kiss1/GPR54 System in Energy Metabolism in Major Metabolic Organs

“…In mHypoA-50 cells differentiated from the AVPV region, relaxin-3 cannot significantly affect Kiss1 expression. This work further illustrates that the insulin superfamily regulates energy homeostasis and reproductive balance by affecting Kiss1 ARC [59]. Thus, the hypothalamic Kiss1/GPR54 system may mediate the regulation of peripheral hormones on the pubertal sexual maturation, feeding, physical activity, and energy expenditure of the organism (discussed in later sections), but more research is needed.…”

Differential Level of RXFP3 Expression in Dopaminergic Neurons Within the Arcuate Nucleus, Dorsomedial Hypothalamus and Ventral Tegmental Area of RXFP3-Cre/tdTomato Mice

“…Further studies to investigate the potential expression and function of RXFP3 within other regions of the pituitary gland, are nonetheless warranted. For example, RXFP3 expression was recently detected in the LβT2 mouse pituitary gonadotroph cell line ( Kanasaki et al, 2019 ), and data from the Genotype-Tissue Expression (GTEx) project describes RXFP3 expression within human pituitary (and adrenal) samples 1 . The potential source of relaxin-3 that might access these receptors is unknown, however.…”