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The Modulation of Aromatase and Estrogen Receptor Alpha in Cultured Human Dermal Papilla Cells by Dexamethasone: A Novel Mechanism for Selective Action.

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Presentation on theme: "The Modulation of Aromatase and Estrogen Receptor Alpha in Cultured Human Dermal Papilla Cells by Dexamethasone: A Novel Mechanism for Selective Action."— Presentation transcript:

1 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?  M. Julie Thornton, Louisa D. Nelson, Anthony H. Taylor, M. Pattie Birch, Ian Laing, Andrew G. Messenger  Journal of Investigative Dermatology  Volume 126, Issue 9, Pages (September 2006) DOI: /sj.jid Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Human dermal papilla cells express mRNA for ERα, ERβ, and aromatase in culture. Ethidium bromide-stained RT-PCR gels showing the expression of ERα, ERβ, aromatase, and GAPDH mRNA from cultured dermal papilla cells derived from five different patients: Numbers 1–5 denote the five different dermal papilla cell cultures, lane 6 (+) is a human myometrium sample that acted as a positive control for ERα and GAPDH or a human ovary sample that acted as a positive control for ERβ and aromatase. The final lane is a RT control for the assay. Size markers for the 100bp DNA marker (L) are shown to the left of the figure. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 ERα mRNA expression in cultured human dermal papilla cells is reduced by dexamethasone, but not by androgens and estrogens. (a) Ethidium bromide-stained RT-PCR gels showing changes in the levels of ERα mRNA levels in untreated cultured human dermal papilla cell lines (Ctrl, lane a) or when treated for 24hours with either, 10nm estrone (E1, lane b), 10nm 17β-estradiol (E2, lane c), 100nm tamoxifen (Tam, lane d) a combination of 100nm tamoxifen, and 10nm E2 (Tam/E2, lane e), 10nm testosterone (T, lane f), 10nm 5α-DHT (lane g), 10nm 5α-androstane-3α, 17β-diol (Diol 1, lane h), 10nm 5α-androstane-3β, 17β-diol (Diol 2, lane i), or 100nm dexamethasone (Dex, lane j). Numbers to the right indicate the individual cell lines. (b) Graphical depiction of grouped data from (a) after correction for individual GAPDH levels (data not shown). Messenger RNA levels are presented as the mean±SEM and analyzed against the untreated controls. (*P<0.05; Student's t-test with Welch's correction; n=5). Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 Androgens, estrogens, and glucocorticoids have no effect on the expression of ERβ mRNA in cultured human dermal papilla cells. (a) Ethidium bromide-stained RT-PCR gels showing changes in the levels of ERβ mRNA levels in untreated cultured human dermal papilla cell lines (Ctrl, lane a) or when treated for 24hours with either, 10nm estrone (E1, lane b), 10nm 17β-estradiol (E2, lane c), 100nm tamoxifen (Tam, lane d) a combination of 100nm tamoxifen and 10nm E2 (Tam/E2, lane e), 10nm testosterone (T, lane f), 10nm 5α-DHT (lane g), 10nm 5α-androstane-3α, 17β-diol (Diol 1, lane h), 10nm 5α-androstane-3β, 17β-diol (Diol 2, lane i), or 100nm dexamethasone (Dex, lane j). Numbers to the right indicate the individual cell lines. (b) Graphical depiction of grouped data from (a) after correction for individual GAPDH levels. Messenger RNA levels are presented as the mean±SEM and analyzed against the untreated controls. (Data are not significantly different; Student's t-test with Welch's correction; n=5). Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 Dexamethasone upregulates the expression of aromatase mRNA in cultured human dermal papilla cells, but androgens and estrogens have no effect. (a) Ethidium bromide-stained RT-PCR gels showing changes in the levels of aromatase mRNA levels in untreated cultured human dermal papilla cell lines (Ctrl, lane a) or when treated for 24hours with either, 10nm estrone (E1, lane b), 10nm 17β-estradiol (E2, lane c), 100nm tamoxifen (Tam, lane d) a combination of 100nm tamoxifen and 10nm E2 (Tam/E2, lane e), 10nm testosterone (T, lane f), 10nm 5α-DHT (lane g), 10nm 5α-androstane-3α, 17β-diol (Diol 1, lane h), 10nm 5α-androstane-3β, 17β-diol (Diol 2, lane i), or 100nm dexamethasone (Dex, lane j). Numbers to the right indicate the individual cell lines. (b) Graphical depiction of grouped data from (a) after correction for individual GAPDH levels (data not shown). Messenger RNA levels are presented as the mean±SEM and analyzed against the untreated controls. (*P<0.05; Student's t-test with Welch's correction; n=5). Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

6 Figure 5 Human dermal papilla cells express ERα and ERβ protein in culture. Immunohistochemical localization of ERα and ERβ in cultured dermal papilla cells derived from human non-balding scalp hair follicles. Bound antibody was visualized with diaminobenzadine. (a) Negative control, where the primary antibody was omitted. (b) Expression of ERα seen distributed throughout the cytoplasm. (c) Expression of ERβ, which was confined specifically to the nucleus. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

7 Figure 6 The active androgens are testosterone and 5α-DHT. Both bind to the androgen receptor with a high affinity and the active estrogen is 17β-estradiol, which binds to both estrogen receptors with similar affinity. However, humans also secrete large amounts of the precursor steroids dihydroepiandrosterone sulfate and androstenedione from the adrenal cortex, which can be converted to the more potent androgens and estrogens by the appropriate enzymes. DHT may be further metabolized by 3β-hydroxysteroid dehydrogenase to 5α-androstane-3β, 17β-diol, which can interact with both ERα and ERβ, or by 3α-hydroxysteroid dehydrogenase to its isomer 5α-androstane-3α, 17β-diol which has weak androgenic effects. A number of different 17β-hydroxysteroid dehydrogenases regulate different oxidative and reductive pathways. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions


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