The modulation of aromatase and estrogen receptor alpha in cultured human dermal papilla cells by dexamethasone: A novel mechanism for selective action of estrogen via estrogen receptor beta?

Abstract

Steroid hormones have important modulatory effects on the hair follicle, but the mechanisms by which they regulate human hair growth are still poorly understood. It is now clear that there are two distinct estrogen receptors (estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ)) that bind 17β-estradiol. Since the follicular dermal papilla is known to control hair growth, and steroid hormones regulate receptor and aromatase expression in other tissues, we tested the hypothesis that steroid hormones would similarly modulate estrogen receptor and/or aromatase expression in cultured dermal papilla cells derived from human hair follicles. Primary cultures of non-balding occipital and frontal scalp and beard dermal papilla cells (n=10) were established. Immunocytochemical studies showed the expression of ERα in both the cytoplasm and nucleus, whereas ERβ was confined to the nuclei. The cells derived from occipital scalp were also incubated for 24 hours with 10 nM of either 17β-estradiol, estrone, testosterone, 5α-dihydrotestosterone, 5α-androstane-3α, 17β-diol, 5α-androstane-3β, 17β-diol, or 100 nM tamoxifen or dexamethasone in phenol red-free, serum-free medium to measure the steady-state levels of ERα, ERβ, and aromatase mRNA by semiquantitative reverse transcriptase-PCR. Although androgens and estrogens did not alter ERα mRNA levels, treatment with dexamethasone significantly reduced ERα levels to 38% of the untreated control. By contrast, ERβ mRNA levels were unaffected by any steroid treatment. Furthermore, dexamethasone significantly stimulated the expression of aromatase mRNA approximately 9-fold. Aromatase activity, assayed by the tritiated water method, was stimulated in both frontal scalp and beard dermal papilla cell cultures by dexamethasone. These observations provide evidence for a glucocorticoid-dependent mechanism whereby the selective action of estradiol via ERβ may be promoted. Additionally, upregulation of aromatase combined with downregulation of ERα provides a basis for selective action of estradiol produced locally by autocrine or paracrine mechanisms. © 2006 The Society for Investigative Dermatology.