17 beta-Estradiol and ICI-182780 regulate the hair follicle cycle in mice through an estrogen receptor-alpha pathway

Estradiol (E-2) applied topically twice weekly to mouse skin at doses as lo w as 1 nmol inhibited hair growth by blocking the transition of the hair fo llicle from the resting phase (telogen) to the growth phase (anagen). In co ntrast, application of less than or equal to 10 nmol of other steroids prod uced limited inhibition. Topical treatment with the estrogen receptor (ER) antagonist ICI-182780 reversed the effects of E-2, and when applied alone, ICI-182780 caused a telogen-to-anagen transition. Both Eg and ICI-182780 we re highly effective at their site of application but not at distant sites, indicating the direct rather than secondary systemic nature of their effect s. Western analysis detected a 65-kDa ER-alpha immunoreactive dermal protei n, and Northern analysis revealed the presence of a 6.7-kb ER-alpha mRNA. A ribonuclease protection assay confirmed the presence of ER-alpha transcrip ts but failed to detect ER-beta transcripts. These findings implicate a ski n-specific ER-alpha pathway in the regulation of the hair follicle cycle.