Papel da prolactina na regulação da expressão de kisspeptina e secreção do hormônio luteinizante em fêmeas

Abstract

Prolactin (PRL) exerts an inhibitory effect on the activity of the hypothalamic-pituitary-gonadal (HPG) axis. Kisspeptin (Kp) has a pivotal role in the regulation of fertility, due to its potent stimulatory action on the secretion of gonadotropin, luteinizing hormone (LH) and follicle stimulating hormone (FSH). In rodents, kisspeptin neurons are located mainly in anteroventral periventricular nucleus (AVPV) of the preoptic area (POA) and in arcuate nucleus (ARC) of the hypothalamus, and are known to express PRL receptors. This study aimed to evaluate the effect of PRL on the expression of kisspeptin and LH secretion in lactating and virgin ovariectomized (OVX) rats. Lactating rats perfused on the lactation day 8 displayed high plasma levels of PRL, and reduced expression of Kp in the ARC and concentration of plasma LH. Blockade of PRL release with bromocriptine resulted in increased expression of Kp in the ARC, which was reversed by co-administration of ovine PRL (oPRL). Bromocriptine caused a significant but only slight increase in LH levels. Thus, PRL decreases Kp expression in the ARC during lactation, but this effect is only partially responsible for the inhibition of LH secretion. OVX rats showed high expression of Kp in the ARC. Both subcutaneous and intracerebroventricular treatment with oPRL in OVX rats significantly decreased Kp expression in ARC and plasma LH levels. This effect of PRL was similar to the classical negative-feedback effect of estradiol, reinforcing the physiological relevance of this inhibitory mechanism. Additionally, the expression Kp-immunoreactive fibers in the AVPV was stimulated by estradiol but not altered by oPRL. Thus, PRL effectively suppresses the expression of Kp in ARC, which is associated with inhibition of LH secretion. Our findings suggest a new mechanism through which PRL is able to regulate the secretion of LH.