Specific Activation of Estrogen Receptor Alpha and Beta Enhances Male Sexual Behavior and Neuroplasticity in Male Japanese Quail

Two subtypes of estrogen receptors (ER), ERα and ERβ, have been identified in humans and numerous vertebrates, including the Japanese quail. We investigated in this species the specific role(s) of each receptor in the activation of male sexual behavior and the underlying estrogen-dependent neural plasticity. Castrated male Japanese quail received empty (CX) or testosterone-filled (T) implants or were daily injected with the ER general agonist diethylstilbestrol (DES), the ERα-specific agonist PPT, the ERβ-specific agonist DPN or the vehicle, propylene glycol. Three days after receiving the first treatment, subjects were alternatively tested for appetitive (rhythmic cloacal sphincter movements, RCSM) and consummatory aspects (copulatory behavior) of male sexual behavior. 24 hours after the last behavioral testing, brains were collected and analyzed for aromatase expression and vasotocinergic innervation in the medial preoptic nucleus. The expression of RCSM was activated by T and to a lesser extent by DES and PPT but not by the ERβagonist DPN. In parallel, T fully restored the complete sequence of copulation, DES was partially active and the specific activation of ERα or ERβ only resulted in a very low frequency of mount attempts in few subjects. T increased the volume of the medial preoptic nucleus as measured by the dense cluster of aromatase-immunoreactive cells and the density of the vasotocinergic innervation within this nucleus. DES had only a weak action on vasotocinergic fibers and the two specific ER agonists did not affect these neural responses. Simultaneous activation of both receptors or treatments with higher doses may be required to fully activate sexual behavior and the associated neurochemical events

Sex Differences in the Cerebellum and Frontal Cortex: Roles of Estrogen Receptor Alpha and Sex Chromosome Genes

Most neurobehavioral diseases are sexually dimorphic in their incidence, and sex differences in the brain may be key for understanding and treating these diseases. Calbindin (Calb) D28K is used as a biomarker for the well-studied sexually dimorphic nucleus, a hypothalamic structure that is larger in males than in females. In the current study weanling C56BL/6J mice were used to examine sex differences in the Calb protein and message focusing on regions outside of the hypothalamus. A robust sex difference was found in Calb in the frontal cortex (FC) and cerebellum (CB; specifically in Purkinje cells); mRNA and protein were higher in females than in males. Using 2 mouse lines, i.e. one with a complete deletion of estrogen receptor alpha (ERα) and the other with uncoupled gonads and sex chromosomes, we probed the mechanisms that underlie sexual dimorphisms. In the FC, deletion of ERα reduced Calb1 mRNA in females compared to males. In addition, females with XY sex chromosomes had levels of Calb1 equal to those of males. Thus, both ERα and the sex chromosome complement regulate Calb1 in the FC. In the CB, ERα knockout mice of both sexes had reduced Calb1 mRNA, yet sex differences were retained. However, the sex chromosome complement, regardless of gonadal sex, dictated Calb1 mRNA levels. Mice with XX chromosomes had significantly greater Calb1 than did XY mice. This is the first study demonstrating that sex chromosome genes are a driving force producing sex differences in the CB and FC, which are neuoranatomical regions involved in many normal functions and in neurobehavioral diseases