Summary
Recent studies have revealed that sex hormones manifest a variety of biological and
immunological effects in the skin. Pregnancy, menstruation and the menopause modulate
the natural course of psoriasis, indicating a female hormone-induced regulation of
skin inflammation. Estrogen in vitro down-regulates the production of the neutrophil,
type 1 T cell and macrophage-attracting chemokines, CXCL8, CXCL10, CCL5, by keratinocytes,
and suppressesIL-12 production and antigen-presenting capacity while enhancing anti-inflammatory
IL-10 production by dendritic cells. These data indicate that estrogen may attenuate
inflammation in psoriatic lesions. Estrogen, alone or together with progesterone,
prevents or reverses skin atrophy, dryness and wrinkles associated with chronological
or photo-aging. Estrogen and progesterone stimulate proliferation of keratinocytes
while estrogen suppresses apoptosis and thus prevents epidermal atrophy. Estrogen
also enhances collagen synthesis, and estrogen and progesterone suppress collagenolysis
by reducing matrix metalloproteinase activity in fibroblasts, thereby maintaining
skin thickness. Estrogen maintains skin moisture by increasing acid mucopolysaccharide
or hyaluronic acid levels in the dermis. Progesterone increases sebum secretion. Estrogen
accelerates cutaneous wound healing stimulating NGF production in macrophages, GM-CSF
production in keratinocytes and bFGF and TGF-β1 production in fibroblasts, leading
to the enhancement of wound re-innervation, re-epithelialization and granulation tissue
formation. In contrast, androgens prolong inflammation, reduce deposition of extracellular
matrix in wounds, and reduce the rate of wound healing. Estrogen enhances VEGF production
in macrophages, an effect that is antagonized by androgens and which may be related
to the development of granuloma pyogenicum during pregnancy. These regulatory effects
of sex steroids may be manipulated as therapeutic or prophylactic measures in psoriasis,
aging, chronic wounds or granuloma pyogenicum.
Abbreviations:
AR (androgen receptor), CBP (CREB-binding protein), E2 (17β-estradiol), ER (estrogen receptor), MIF (macrophage migration inhibitory factor), MMP (matrix metalloproteinase), TIMP (tissue inhibitor of metalloproteinase)Keywords
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Biography
Naoko Kanda received MD and PhD in Faculty of Medicine, Tokyo University, Tokyo, Japan in 1987 and 1994, respectively. She is currently working as an associate professor in Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan, since 2002. She was a postdoctoral research fellow in Department of Surgery, UCLA, School of Medicine, USA in 1991 and 1992, a research associate in John Wayne Cancer Institute, USA in 1992 and 1993, and was an assistant professor in Department of Dermatology, University of Tokyo, Japan from 1993 to 1999, and was a Lecturer in Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan from 1999 to 2002. Her research interests include cutaneous immunology, allergy, melanoma, cytokine, and chemokine.
Article info
Publication history
Accepted:
October 29,
2004
Received in revised form:
October 26,
2004
Received:
September 3,
2004
Identification
Copyright
© 2004 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
