Lena Sahlin, PhD
Effects of oestrogen treatment
A second type of estrogen receptor, named beta (ER-beta), was discovered in 1996. In order to elucidate if the regulation of the "classic" ER-alpha and ER-beta is different we have studied the expression of the two subtypes in the female reproductive tract during different hormonal conditions. In addition, we study the cross-talk between ERs and the other steroid hormone receptors.
The levels of ER-alpha and progesterone receptor are both decreased at term. These changes are concordant with a decrease in collagen concentration and an increase in collegen solubility, indicating increased collagen metabolism in the cervix. There is a significant increase of ER-beta expression at term pregnancy. The up-regulation of ER-beta in human cervix before parturition suggests a specific role of this receptor during cervical ripening.
The leukocytes within the human cervical tissue were shown, by immunohistochemistry, to express ER-beta. Several leukocyte subsets were shown to express ER-beta and metalloproteinases -2 and -9 (MMP-2 and -9). Thus, estrogens may have a direct effect on leukocytes mediated via activation of ER-beta resulting in recruitment and activation of leukocyte subsets and an increase in production of key factors (such as cytokines and metalloproteinases) important for cervical remodeling. Human periferal leukocytes express both ER-alpha and ER-beta protein. In monocytes there are mRNAs for both ER-alpha and ER-beta while polymorphonuclear leukocytes express only modified mRNAs. Another approach to study genes regulated by specific ER ligands is the microarray technology. We have treated with selective ER agonists and are now studying the changed gene expression in leukocytes, related to which ER that was activated. The results are verified by real-time PCR and Western blot.
Selected publications
Impaired leukocyte influx in cervix of postterm women not responding to prostaglandin priming.
Reprod Biol Endocrin (2008) 6:36.
Studies on estrogen receptor (ER) {alpha} and {beta} responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists.
Journal of Endocrinology (2007) 194(1):101-19.
