Estrogen and the aging brain of male rats

Abstract

Gonadal steroid hormones exert an influence on many aspects of neurobiology in men, including memory, learning and sexual dysfunction. Though testosterone is the main circulating gonadal steroid hormone in males, estradiol is also important, and together these hormones play complementary roles. While the specific roles of estrogen have been studied to some extent in young adults, little is known during aging, when sexual behavior can become impaired. I used a rodent model to examine estradiol’s role in sexual behavior and gene expression in 3 regions, selected for their importance in behavioral neuroendocrine functions and high concentrations of estrogen receptors: the medial preoptic area (mPOA), medial amygdala (MeA), and bed nucleus of the stria terminalis (BnST). My studies focused first on how age and sexual experience affects expression and activation of estrogen receptor α (ERα) and androgen receptor (AR) after sexual behavior in aging intact males. Quantification of neurons expressing hormone receptors in the mPOA revealed that neither ERα nor androgen receptor (AR) showed an age-related change in expression in the mPOA. While both ERα and AR were activated after copulation, the age-related changes were specific to ERα in the central mPOA. There were only mild deficits in sexual behavior. Serum estradiol was also elevated in both aged and copulating animals, but estradiol concentrations only correlated with sexual behavior in aged animals. In a second study, I determined how hormone deprivation (castration) and replacement with estradiol caused changes to gene expression in the mPOA, BnST and MeA. Each region had unique patterns of gene expression in response to aging and estradiol treatment. The mPOA only had changes in expression as a result of hormone administration, while the BnST had primarily age-related changes. The MeA had the greatest number of affected genes, mainly interactions between estradiol treatment and aging. These studies emphasize the importance of estradiol in aging males, and the need for continued study on its role in neuroendocrine and sexual function.