Sex Hormone Receptors and Regulation of Gene Expression; Tissue Specificity of Traditional and Alternative Hormone Replacement Therapies; Molecular, Cellular, and Radiologic Evaluations of Adipose Characteristics
Sex hormones (estrogens, progestogens, and androgens) exert their effects on target tissues through specific hormone receptors. Alterations in the levels of these hormones through aging, menopause, or pharmacologic interventions have diverse effects on different target tissues, sometimes promoting health in one tissue and disease in another. Our previous work demonstrated that reproductive and non-reproductive tissues from non-human primates express both the classical ER (ERalpha) and a newly discovered estrogen receptor (ERbeta). Coronary arteries from females as well as males were found to express relatively high levels of ERbeta mRNA compared to ERalpha, suggesting this receptor could play a role in the protective effects of estrogens against atherosclerosis. ERbeta/ERalpha mRNA ratios were found to be highest in hippocampus and hypothalamus, intermediate in ovary, artery and uterus, and low in mammary and hepatic tissues. Since these receptors have unique properties, their absolute and relative expression may be important factors in tissue-specific responses to estrogen(s) and other hormones. Some phytoestrogens, for example, have a higher affinity for ERbeta.
A primary research interest relates to the effects of hormones and hormone-like compounds on gene expression on traditional and non-traditional target tissues and the role of the estrogen receptors, ERalpha and ERbeta. For example, arterial expression of ERalpha is inversely related to atherosclerosis, and may influence susceptibility to the disease. These studies employ functional genomics to explore hormone effects on global gene expression.
We are also investigating the relationships between imaging, molecular, and cellular phenotypes of adipose and other tissues in human and non-human primates.
We are exploring relationships between vascular disease and bone metabolism, with an emerging focus on the role of Vitamin D in human studies.