Abstract
Female sexual behavior is controlled by central estrogenic action in the ventromedial nucleus of the hypothalamus (VMN). This region plays a pivotal role in facilitating sex-related behavior in response to estrogen stimulation via neural activation by several neurotransmitters, including histamine, which participates in this mechanism through its strong neural potentiating action. However, the mechanism through which estrogen signaling is linked to the histamine system in the VMN is unclear. This study was undertaken to investigate the relationship between estrogen and histamine receptor subtype H1 (H1R), which is a potent subtype among histamine receptors in the brain. We show localization of H1R exclusively in the ventrolateral subregion of the female VMN (vl VMN), and not in the dorsomedial subregion. In the vl VMN, abundantly expressed H1R were mostly colocalized with estrogen receptor α. Intriguingly, H1R mRNA levels in the vl VMN were significantly elevated in ovariectomized female rats treated with estrogen benzoate. These data suggest that estrogen can amplify histamine signaling by enhancing H1R expression in the vl VMN. This enhancement of histamine signaling might be functionally important for allowing neural excitation in response to estrogen stimulation of the neural circuit and may serve as an accelerator of female sexual arousal.
Highlights
The ventromedial nucleus of the hypothalamus (VMN) is a brain region governing female reproductive functions and sexual behavior [1,2,3,4], and is anatomically divided into the ventrolateral and dorsomedial subregions
H1R localization in the ventrolateral VMN The mediobasal hypothalamic area is densely innervated by histaminergic nerve terminals that originate from the tuberomammillary nucleus (TM) nucleus
Confocal microscopic images at high magnification showed the subcellular localization of the two receptors, with the nuclear receptor ERa preferentially located within nuclei and excluded from nucleoli and the G protein-coupled receptor H1R exclusively located in the cell membrane
Summary
The ventromedial nucleus of the hypothalamus (VMN) is a brain region governing female reproductive functions and sexual behavior [1,2,3,4], and is anatomically divided into the ventrolateral (vl) and dorsomedial (dm) subregions. Central estrogen affects the estrogen-sensitive neural group in the VMN, and in the vl VMN and the neural circuit controlling female sexual behavior is ‘‘turned on’’. This primary estrogenic action is thought to be a genomic effect mediated by estrogen receptor (ER) [7], which is abundantly present in the vl VMN [1,8,9]. Histamine is a potent arousal-related neurotransmitter that typically excites neurons by causing depolarization, which increases firing latency [10,11,12]. Our finding of colocalization of ERa and H1R in the vl VMN led us to hypothesize that there could be a functional interaction between estrogen signaling and histamine receptors
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