Exercise-induced muscle hormone “irisin” controls luteinizing hormone and follicle-stimulating hormone secretion by bovine gonadotrophs

Irisin is a hormone secreted by muscle in response to exercise. The irisin receptor (IrisinR) is a heterodimer of integrin alpha V (ITGAV) and integrin beta 5 (ITGB5) subunits. Since irisin may mediate some beneficial effects of exercise on animal reproduction, we tested the hypothesis that bovine gonadotrophs express IrisinR and irisin stimulates luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion by gonadotrophs. Reverse transcription polymerase chain reaction was used to detect the mRNA expression of both ITGAV and ITGB5 in the anterior pituitary glands (APs) of post pubertal heifers and mouse gonadotroph cell line “LβT2.” Western blotting was used to detect protein expression in bovine APs. Immunofluorescence microscopy, utilizing the same antibody, visualized IrisinR on the plasma membrane of majority of gonadotrophs. We prepared AP cells from healthy postpubertal heifers, cultured them for 3.5 d, and treated them with increasing concentrations (0, 0.01, 0.1, 1, or 10 nM) of irisin for 5 min before either no treatment or gonadotropin-releasing hormone (GnRH) stimulation. After 2 h, media were harvested for LH and FSH assays. Irisin (0.1–10 nM) stimulated basal LH and FSH secretion, and these stimulatory effects were inhibited by the extracellular signal-regulated kinase or SMAD pathway inhibitors. In the presence of GnRH, irisin at 0.01–1 nM stimulated LH and FSH secretion. A higher dose of irisin (10 nM), however, suppressed the GnRH-induced LH and FSH levels. In conclusion, bovine gonadotrophs expressed IrisinR, and irisin controlled LH and FSH secretion from bovine gonadotrophs.