Major reproductive events such as menstruation, ovulation, implantation, and cervical ripening are characterized by an increased number of invading leukocytes in the tissues. Sex steroid hormones, particularly estrogens, play an important role in these dynamic changes in the female reproductive tract. Estrogens have also been implicated in the pathogenesis of many common pathological conditions associated with leukocyte infiltration and immunological dysfunction, such as auto-immune diseases and atherosclerosis. Although the two estrogen receptor (ER) subtypes, ERα and ERβ, have been found in different leukocyte populations in tissues and in peripheral blood, there is still very little known about functional activity and importance of ERs in blood cells. To elucidate the different roles for ERα and ERβ in peripheral blood leukocytes, we used microarray gene expression profiling of rat peripheral blood leukocytes subjected to in vivo treatment with estradiol (E₂), the selective ERα agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), and the selective ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN). We report the identification of genes that were commonly regulated by E₂, PPT, and DPN, and genes that were regulated either by the ERα or ERβ agonist. Further confirmatory analyses of the selected regulated genes 12-lipoxygenase, fibulin-1, furin, and calgranulin B are also presented. These results were then compared with those from the uterine tissue of the same animals. Our study demonstrates that peripheral blood leukocytes are responsive to estrogens. E₂ and selective ERα and ERβ agonists regulate a number of genes that may contribute to inflammation and remodeling of the extracellular matrix.

There are well known differences between males and females in hearing. In the present study, the role of estrogen receptor-β (ER-β; listed as ESR2 in the MGI Database) in hearing was investigated by comparing hearing and morphology of the inner ear in ER-β knock-out mice (ER-β^−/−) with that of wild-type (WT) littermates. Hearing was analyzed with auditory brainstem response audiometry at 3 and 12 months. The ER-β^−/− mice were deaf at 1 year of age, and the morphological analysis showed absence of hair cells and loss of the whole organ of Corti initiated in the basal turn of the cochlea. Furthermore, in ER-β^−/−, but not in WT mice, the spiral ganglion was lacking many of its neurons. Immunostaining showed the presence of both ER-α (listed as ESR1 in the MGI Database) and ER-β in the nuclei of some neurons in the inner ear in WT mice, but no ER-β was found in the ER-β^−/− mice as expected. ER-α staining was predominant in the nuclei of large neurons and ER-β in nuclei of small neurons and fibroblasts. These results reveal that both ERs are present in the inner ear at specific localizations suggesting subtype-specific functions. It is concluded that ER-β is important for the prevention of age-related hearing loss. These findings strengthen the hypothesis that estrogen has a direct effect on hearing functions.