Abstract
Testosterone is involved in male sexual, parental and aggressive behaviors through the androgen receptor (AR) and estrogen receptor (ER) α expressed in the brain. Although several studies have demonstrated that ERα and AR in the medial preoptic area (MPOA) are required for exhibiting sexual and aggressive behaviors of male mice, the molecular characteristics of ERα- and AR-expressing cells in the mouse MPOA are largely unknown. Here, we performed in situ hybridization for neurotransmitters and neuropeptides, combined with immunohistochemistry for ERα and AR to quantitate and characterize gonadal steroid receptor-expressing cells in the MPOA subregions of male mice. Prodynorphin, preproenkephalin (Penk), cocaine- and amphetamine-related transcript, neurotensin, galanin, tachykinin (Tac)1, Tac2 and thyrotropin releasing hormone (Trh) have distinct expression patterns in the MPOA subregions. Gad67-expressing cells were the most dominant neuronal subtype among the ERα- and AR-expressing cells throughout the MPOA. The percentage of ERα- and AR-immunoreactivities varied depending on the neuronal subtype. A substantial proportion of the neurotensin-, galanin-, Tac2- and Penk-expressing cells in the MPOA were positive for ERα and AR, whereas the vast majority of the Trh-expressing cells were negative. These results suggest that testosterone exerts differential effects depending on both the neuronal subtypes and MPOA subregions.
Highlights
Androgens such as testosterone play a central role in the regulation of the sexual, parental and aggressive behaviors of male animals through a direct action on androgen receptors (AR) and an indirect action on estrogen receptors (ERs), such as ERα and ERβ after being aromatized into estradiol in the brain[1,2,3,4]
The brain atlas identified several nuclei in the POA region, such as the medial preoptic nucleus (MPN), posterodorsal preoptic nucleus (PD) and ventrolateral preoptic nucleus (VLPO), the relatively large region outside of these nuclei sandwiched between the anterior commissure and the optic tract remains unnamed or is collectively referred to as the medial preoptic area (MPOA) (Allen brain atlas: http://www.brain-map.org/)[29]
In our study, we subdivided this broad MPOA into four regions: the dorsomedial part of the MPOA, central part of the MPOA, ventral part of the MPOA, and ventrolateral part of the MPOA
Summary
Androgens such as testosterone play a central role in the regulation of the sexual, parental and aggressive behaviors of male animals through a direct action on androgen receptors (AR) and an indirect action on estrogen receptors (ERs), such as ERα and ERβ after being aromatized into estradiol in the brain[1,2,3,4]. A recent report showed that the ablation of galanin-expressing neurons in the MPOA inhibited paternal behaviors, and the optogenetic activation of galanin-expressing neurons enhanced paternal behaviors towards pups[24], which suggests that neuronal subtypes characterized by the differential expressions of neuropeptides and neurotransmitters in the MPOA may have a distinct role in sexual and parental behaviors. We quantitated the expression of neurotransmitters and neuropeptides for ERα- or AR-expressing cells in each MPOA subregion of male mice, and the expression was delineated using MPOA subregion markers, such as calbindin, oxytocin neurotensin, preproenkephalin (Penk) and vesicular glutamate transporter[2] (Vglut2)[17, 18, 25, 26]
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