17beta-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 low as 1 nmol inhibited hair growth by blocking the transition of the hair follicle from the resting phase (telogen) to the growth phase (anagen). In contrast, application of </=10 nmol of other steroids produced 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 E(2) and ICI-182780 were highly effective at their site of application but not at distant sites, indicating the direct rather than secondary systemic nature of their effects. Western analysis detected a 65-kDa ER-alpha immunoreactive dermal protein, and Northern analysis revealed the presence of a 6.7-kb ER-alpha mRNA. A ribonuclease protection assay confirmed the presence of ER-alpha transcripts but failed to detect ER-beta transcripts. These findings implicate a skin-specific ER-alpha pathway in the regulation of the hair follicle cycle.
Chanda
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S
Molecular and Cellular Toxicology, Department of Toxicology, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27695, USA.
Robinette
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CL
Couse
J F
JF
Smart
R C
RC
D000287:Administration, Topical; D000818:Animals; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D005260:Female; D000077267:Fulvestrant; D006197:Hair / Q000254:growth & development*; D018859:Hair Follicle / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol