Prolactin locally mediates follicular atresia in hyperprolactinemic vizcachas (Rodentia, Chinchillidae).

Abstract

Infertility in hyperprolactinemic females is attributed to the dysregulation of GnRH release, subsequently affecting gonadotropin levels, and ultimately leading to anovulation. However, in addition to the hypothalamus, prolactin receptor (PRLR) is expressed in ovaries as well, suggesting potential local effects of PRL in cases of hyperprolactinemia. We have developed an experimental model of sulpiride (SPD)-induced hyperprolactinemia using a wild rodent, the plains vizcacha, and studied the implications of pharmacological PRL levels on folliculogenesis and steroid production. Ovaries of SPD females showed a striking number of atretic follicles along with a reduction in the collective number of viable follicles leading to a higher atretic/viable follicle ratio compared to that of control females (CTL) (P < 0.05). In terms of sensitivity to the hormonal environment, SPD ovaries substantially changed their potential responsiveness to pituitary PRL, as evidenced by the three-fold increase in PRLR expression alongside heightened expression of both gonadotropic receptors in comparison to CTL ovaries (P < 0.05). Circulating estradiol (E2) values doubled post-treatment in the SPD females, which also showed higher expressions of aromatase and 17β-hydroxysteroid dehydrogenase, along with both E2 receptors, ERα and ERβ than the CTL group (P < 0.05). Our findings strongly suggest that hyperprolactinemia-dependent dysregulation of ovarian function can be explained at least partially, by PRL direct actions facilitated by the heightened expression of PRLR in follicles and corpora lutea. Possibly these PRL actions synergize with those triggered by gonadotropic hormones ultimately leading to alteration of the steroidogenic pathway, folliculogenesis disruption and increased atresia.