The maternal hormone in the male brain: sexually dimorphic distribution of prolactin signalling in the mouse brain

Abstract

Research of the central actions of prolactin is virtually restricted to females, but this hormone has also documented roles in male physiology and behaviour. Here, we provide the first description of the pattern of prolactin-derived signalling in the male mouse brain, employing the immunostaining of phosphorylated signal transducer and activator of transcription 5 (pSTAT5) after exogenous prolactin administration. Next, we explore possible sexually dimorphic differences by comparing pSTAT5 immunoreactivity in prolactin-supplemented males and females. We also assess the role of testosterone in the regulation of central prolactin signalling in males by comparing intact with castrated prolactin-supplemented males.Prolactin-supplemented males displayed a widespread pattern of pSTAT5 immunoreactivity, restricted to brain centres showing expression of the prolactin receptor. Immunoreactivity for pSTAT5 was present in several nuclei of the preoptic, anterior and tuberal hypothalamus, as well as in the septofimbrial nucleus or posterodorsal medial amygdala of the telencephalon. Conversely, non-supplemented control males were virtually devoid of pSTAT5-immunoreactivity, suggesting that central prolactin actions in males are limited to situations concurrent with substantial hypophyseal prolactin release (e.g. stress or mating). Furthermore, comparison of prolactin-supplemented males and females revealed a significant, female-biased sexual dimorphism, supporting the view that prolactin has a preeminent role in female physiology and behaviour. Finally, in males, castration significantly reduced pSTAT5 immunoreactivity in some structures, including the paraventricular and ventromedial hypothalamic nuclei and the septofimbrial region, thus indicating a region-specific regulatory role of testosterone over central prolactin signalling.

Acute effects of prolactin on hypothalamic prolactin receptor expressing neurones in the mouse

“…Expression of the Prlr and of pSTAT5 in the MPOA has been reported to be sexdependent [6,9]. Nonetheless, our investigations detected little difference in the proportion of prolactin-responsive cells in virgin males, females or lactating females.…”

“…Binding of prolactin to its receptor exerts co-ordinated effects on gene transcription dependent on phosphorylation of the STAT5 transcription factor. Utilising immunohistochemical labelling of phosphorylated STAT5 (pSTAT5) has therefore been an effective method of mapping prolactin-responsive cells [7][8][9][10]. In the central nervous system (CNS), prolactin-induced pSTAT5 is widely distributed in forebrain and brainstem areas [11].…”

Becoming a mother shifts the activity of the social and motivation brain networks in mice

“…There is strong evidence indicating that sexual steroids (late-pregnancy progesterone withdrawal and estradiol surge) plus placental lactogens (late pregnancy) and/or hypophysial prolactin (postpartum) (see Bridges, 2020 ) are needed to induce fully motivated maternal behaviors. Recent work has shown that during pregnancy and postpartum, lactogens are able to influence the SBN nodes ( Salais-López et al., 2017 , 2021 ) that also concentrate estradiol-sensitive cells ( Mitra et al., 2003 ; Simerly et al., 1990 ), whereas the nuclei composing the motivational brain circuitry do not express prolactin receptors ( Kokay et al., 2018 ; Salais-López et al., 2018 ) or few estrogen receptors ( Mitra et al., 2003 ; Simerly et al., 1990 ). Therefore, the influence of pregnancy hormones on motivation must be indirect, e.g.…”

Chronic high prolactin levels impact on gene expression at discrete hypothalamic nuclei involved in food intake

“…Prolactin‐responsive neurons are abundant in the hypothalamus with discrete distribution in specific brain nuclei related to food intake, energy expenditure, and metabolism, such as the arcuate nucleus (ARN), ventromedial nucleus (VMN), and dorsomedial nucleus (DMN), among others. Indeed, the hypothalamus is the cornerstone of food intake regulation and regionally organized nuclei constitute intricate pieces that help to build a coordinated response to metabolic needs, perceived neurally or hormonally.…”