Topical estrogens: their effects on connective tissue synthesis in hairless mouse skin.

Skin is an important target organ for estrogens. The major reported effects of estrogens are as regulators of connective tissue molecules, namely collagen and hyaluronic acid. We investigated the regulation of connective tissue synthesis by topical estrogens in a hairless mouse model of photodamaged skin, which has been previously shown to respond to topical retinoids. The naturally occurring estrogen, 17beta-estradiol (17beta-E) and a close stereoisomer, 17alpha-estradiol (17alpha-E), were found to be as effective as all- trans-retinoic acid in stimulating the development of new connective repair zones in photodamaged skin. Furthermore, 17beta-E and 17alpha-E caused a skin thickening response in normal hairless mouse skin after three daily treatments. Skin thickening is due to water accumulation as a result of estrogen-induced hyaluronan synthesis. Our results show that topical estrogens are important regulators of connective tissue synthesis in photodamaged skin as well as normal skin. These findings are consistent with reports from human studies in which estrogen has been found to stimulate collagen production. We also demonstrated that 17alpha-E, previously thought to be a weak or inactive estrogen, is less potent than 17beta-E, but nonetheless topically effective in stimulating connective tissue synthesis.