Hyperprolactinemia and ovarian function

RULLI, SUSANA B

Ciudad del cabo

Congreso; International Congress of Endocrinology; 2018

Female infertility is often associated with hormonal imbalance and involves alterations of the hypothalamic-pituitary-gonadal function by integrated mechanisms. Hyperprolactinemia is one of the most common endocrine disorders and affects reproductive function. The main regulatory pathway for the secretion of prolactin is the inhibitory action of dopamine by acting through the dopamine D2 receptor. This hypothalamic neurotransmitter suppresses the secretory activity of pituitary lactotropes, reduces the expression of the prolactin gene, and activates several interacting intracellular signaling pathways that inhibit the proliferation of lactotropes. The characterization of mouse models has been useful to understand the role of prolactin in reproduction. In this regard, transgenic female mice overexpressing the human chorionic gonadotropinβ-subunit (hCGβ+ mice) produce high levels of bioactive hCG, and induce the ovarian production of estradiol, testosterone and progesterone. As a consequence of this hormonal imbalance, the females are infertile and develop hyperprolactinemia associated with pituitary lactotrope adenomas in adulthood. A short treatment with the dopamine agonist cabergoline applied to young mice corrects hyperprolactinemia, hyperandrogenism, and hyperprogesteronemia, prevents pituitary overgrowth, normalizes gonadal function, and restores the fertility of hCGβ+ females, even in the presence of high levels of hCG. Interestingly, the phenotype of the transgenic offspring derived from the hCGβ+ females previously treated with cabergoline was also normalized. It is discussed here that hyperprolactinemia is the main cause of the reproductive defects of adult hCGβ+ females that can be prevented by a short-term treatment with cabergoline at the beginning of reproductive age. This treatment may impact on the development of the hypothalamic-pituitary-gonadal axis of the offspring by preventing the phenotypic alterations related to hCG hypersecretion. This potential protective effect of cabergoline against high hCG deserves more detailed consideration, which could be evidenced by the use of a transgenic mouse model with overexpression of hCG.