Oestrogen's masculine side: mediation of mating in male mice

Abstract

This review focuses on the role of oestrogen in male sexual behaviour using oestrogen receptor alpha and beta knockout (ERalphaKO and ERbetaKO) mouse models. ERbetaKO mice are capable of mating and producing offspring, whereas ERalphaKO mice are unable to do either. When ERalphaKO males are treated with testosterone or dihydrotestosterone (DHT), < 50% display mounting behaviour, few intromit and none ejaculate. However, concurrent treatment with testosterone and a dopamine agonist instates masculine sexual behaviour in both male and female ERalphaKO mice. Dopamine content in the preoptic area and associated regions is not affected by oestrogen receptor alpha gene disruption. However, expression of neuronal nitric oxide synthase immunoreactivity is severely reduced in ERalphaKO males compared with wild-type males. These findings, together with studies conducted in aromatase knockout mice, are at odds with the dogma that oestrogen is required during development for expression of male sexual behaviour in adults. However, they do support a role for oestrogens, mediated by oestrogen receptor alpha, in regulation and production of neuronal nitric oxide synthase, which in turn may control dopamine agonist release. As has been shown in male rats, in mice dopamine agonist release is likely to be an essential component of the neural pathway that mediates male sexual behaviour.

Impaired Male Sexual Behavior in Activin Receptor Type II Knockout Mice1

“…Both aromatase and estrogen receptors are expressed in mPOA and mice lacking estrogen receptor a and aromatase demonstrate male reproductive behavioral defects [24,40,41,65,66]. Our data indicate that aromatase gene expression is not affected in mPOA of Acvr2 À/À mice and their serum estrogen levels are comparable with those in control male mice.…”

“…Other factors that are known to affect male sexual behavior include estrogen signaling and aromatase [40,42]. Both aromatase and estrogen receptors are expressed in mPOA and mice lacking estrogen receptor a and aromatase demonstrate male reproductive behavioral defects [24,40,41,65,66].…”

“…Defects in the activity of aromatase or NOS1 in the mPOA [40] or increases in estrogen levels, as observed in ERa-knockout mice, can cause disruption of male reproductive behavior [40,41]. Furthermore, male sexual behavioral defects have been reported in aromatase-knockout mice [24,42].…”

Control of masculinization of the brain and behavior

“…While these two circumscribed effects of sex steroids have served a useful heuristic function, not all sexually dimorphic behaviors differentiate under a sex specific organizational and activational role of gonadal hormones. For example, both male and female mice exhibit male pattern sexual behavior towards females, although females will display such behaviors at lower frequency [16–18]. The frequency of male pattern mating is directly regulated by adult levels of testosterone such that wildtype females supplemented with testosterone mount females as readily as males [19].…”

Testosterone in the central control of penile erection

“…Sur le plan comportemental, les invalidations ubiquitaires des gènes codant l'aromatase Cyp19, les récepteurs ERα et ERβ suggèrent fortement l'implication de la voie de l'aromatisation dans la masculinisation et la déféminisation céré-brales du comportement sexuel par la testostérone [22, [130][131][132][133][134][135][136][137][138][139][140][141][142]. Les résultats sont plus difficiles à interpréter quand il s'agit des modèles génétiques ciblant l'AR.…”