 The objectives of the study are to determine if topically-applied 17-beta estradiol E2, alone or in combination with clobetasol, will produce histological and molecular effects distinguishable from vehicle in human skin. Specifically, the study will focus on regulation of collagen, elastin, and hyaluronic acid production and degradation in human skin, by steroid hormone receptors that are activated by estrogen or clobetasol. The sites to be treated will be buttock, hip, forearm, or facial skin. Subjects will receive between one to twelve vehicle matching solution without any active ingredients, estrogen, andor clobetasol topical applications. Skin biopsies of treated areas will be obtained at baseline and at subsequent timepoints. The study will last up to two weeks. Endpoints will include protein and mRNA levels of collagen, elastin, hyaluronic acid, and other components of skin connective tissue. In addition, we will perform cDNA microanalysis to determine estrogenclobetasol target genes in human skin. The results from our studies will provide new knowledge regarding the molecular basis of skin aging. This new knowledge will enable development of new ways to improve the function of aged skin. 