The prolactinergic system in the brain of mice: sexual differences and changes during motherhood

Abstract Background Prolactin (PRL) is an adenohypophyseal hormone with a key role in maternal and sexual behaviour, among multiple functions. Here, we sought to provide a comprehensive description of the PRLergic system in the brain of mice, describing sex differences and plasticity of this system across reproductive stages in females. Methods We describe the neural prolactinergic system using a PRL antibody validated in Prl-KO mouse tissue. This description was carried out in females in different physiological stages (virgins, virgins with experience with pups and lactating) and males. Results We show PRL-immunoreactive (PRL-ir) somata in several hypothalamic nuclei, including the paraventricular and supraoptic, where we observe variable degrees of co-localization with arginine-vasopressin and oxytocin. PRL-ir fibres span the hypothalamus, amygdala, bed nucleus of the stria terminalis, septum, thalamic, midbrain, and pontine regions. Although the qualitative distribution of PRL-ir remains consistent across both sexes and different physiological states in females, differences arise in the density of PRL-ir cells. Regarding sex differences, PRL-ir neurons are more abundant in the medial preoptic area and paraventricular nucleus of the hypothalamus of females, and in the supraoptic nucleus of males. In addition, we found an increased number of PRL-ir somata in the medial preoptic area, supraoptic and suprachiasmatic nuclei of lactating females as compared to virgins. Interestingly, treatment with bromocriptine, which blocks the release of adenohypophyseal PRL, does not affect PRL-ir in the brain, and there is no significant correlation between brain and serum PRL levels in lactating females. Conclusion Taken together, our data support that brain PRLergic system is shaped by the sex and the reproductive status of the animals and, at least in part, is independent of hypophyseal PRL transported into the brain.