Irisin decreases follicle development in cattle and inhibits theca cell steroidogenesis through focal adhesion kinase signaling.

IN BRIEF: Irisin is a muscle and adipose-derived hormone that is secreted in response to negative energy balance in cattle. We show here that irisin reduced follicle growth and theca cell function.

ABSTRACT: At the onset of lactation, dairy cattle are anestrous owing mainly to a state of negative energy balance. Adipose tissue is mobilized to meet the energy demands of milk production, and this alters the secretion of adipose-derived hormones, called adipokines. Irisin is a myokine/adipokine that may play a role in fertility; plasma concentrations increase in cattle postpartum, and irisin decreased progesterone and estradiol secretion from bovine granulosa cells in vitro. To our knowledge, the effects of irisin on bovine theca cell function in vitro and on follicle growth in vivo have not been reported. We hypothesized that irisin negatively affects theca cell function in vitro and causes follicle regression in vivo using well-established bovine models. Under physiological concentrations of insulin (0.2 ng/mL), irisin did not affect glucose uptake, but decreased testosterone secretion and stimulated PTK2 and MTOR phosphorylation. Inhibiting PTK2 activity abolished the ability of irisin to decrease testosterone secretion. Injection of irisin directly into a growing follicle in vivo caused follicle regression. We conclude that irisin decreases bovine theca cell steroidogenesis through PTK2 signaling, and combined effects on theca and granulosa cells cause follicle regression.