Loss of TRPC2 function in mice alters sex differences in brain regions regulating social behaviors.

The transient receptor potential cation channel 2 (TRPC2) conveys pheromonal information from the vomeronasal organ (VNO) to the brain. Both male and female mice lacking this gene show altered sex-typical behavior as adults. We asked whether TRPC2, highly expressed in the VNO, normally participates in the development of VNO-recipient brain regions controlling mounting and aggression, two behaviors affected by TRPC2 loss. We now report significant effects of TRPC2 loss in both the posterodorsal aspect of the medial amygdala (MePD) and ventromedial nucleus of the hypothalamus (VMH) of male and female mice. In the MePD, a sex difference in neuron number was eliminated by the TRPC2 knockout (KO), but the effect was complex, with fewer neurons in the right MePD of females, and fewer neurons in the left MePD of males. In contrast, MePD astrocytes were unaffected by the KO. In the ventrolateral (vl) aspect of the VMH, KO females were like wildtype (WT) females, but TRPC2 loss had a dramatic effect in males, with fewer neurons than WT males and a smaller VMHvl overall. We also discovered a glial sex difference in VMHvl of WTs, with females having more astrocytes than males. Interestingly, TRPC2 loss increased astrocyte number in males in this region. We conclude that TRPC2 normally participates in the sexual differentiation of the mouse MePD and VMHvl. These changes in two key VNO-recipient regions may underlie the effects of the TRPC2 KO on behavior.

Fulfilling desire: evidence for negative feedback between men's testosterone, sociosexual psychology, and sexual partner number.

Across human societies and many nonhuman animals, males have greater interest in uncommitted sex (more unrestricted sociosexuality) than do females. Testosterone shows positive associations with male-typical sociosexual behavior in nonhuman animals. Yet, it remains unclear whether the human sex difference in sociosexual psychology (attitudes and desires) is mediated by testosterone, whether any relationships between testosterone and sociosexuality differ between men and women, and what the nature of these possible relationships might be. In studies to resolve these questions, we examined relationships between salivary testosterone concentrations and sociosexual psychology and behavior in men and women. We measured testosterone in all men in our sample, but only in those women taking oral contraception (OC-using women) in order to reduce the influence of ovulatory cycle variation in ovarian hormone production. We found that OC-using women did not differ from normally-ovulating women in sociosexual psychology or behavior, but that circulating testosterone mediated the sex difference in human sociosexuality and predicted sociosexual psychology in men but not OC-using women. Moreover, when sociosexual psychology was controlled, men's sociosexual behavior (number of sexual partners) was negatively related to testosterone, suggesting that testosterone drives sociosexual psychology in men and is inhibited when those desires are fulfilled. This more complex relationship between androgens and male sexuality may reconcile some conflicting prior reports.