Physiological and functional changes in the stratum corneum restored by oestrogen in an ovariectomized mice model of climacterium

Abstract

Significant decreases in hormonal levels at menopause induce physiological and functional discomfort in the skin. Representative changes at menopause are based on so-called dry skin. However, there is no evidence to explain the mechanism, even though hydration of the stratum corneum (SC) in women at menopause is comparable with that at premenopause but is enhanced by hormone replacement therapy. This study objective was to evaluate structural and functional changes in the SC in ovariectomized mice model of menopause. Hydration of the SC, recovery of the permeability barrier function, integrity and cohesion of the SC, and irritant dermatitis were analysed in mice that underwent ovariectomy with or without replacement of 17ß-estradiol. In ovariectomized mice, hydration of the SC was reduced, recovery of permeability barrier function after acute disruption was impaired, and integrity of the SC was weakened and was associated with increased cohesion and increased levels of irritant dermatitis. Oestrogen replacement treatment restored all changes. Immunohistochemistry revealed reduced levels of expression of desmoglein-1 and differentiation markers of epidermis in ovariectomized mice compared with control mice and mice with oestrogen replacement treatment. These changes might be directly associated with weakened integrity and impaired permeability barrier function of the SC in ovariectomized mice. This study results reveal that so-called dry skin at menopause is caused by not only lower hydration of the SC but also complicated structural and functional changes in the SC and skin.

Aging-associated alterations in epidermal function and their clinical significance

“…Similarly, oral supplements of flaxseed and borage oil increased stratum corneum hydration, while decreasing transepidermal water loss rates in humans [129]. In addition, estrogen replacement can improve multiple epidermal functions, including permeability barrier homeostasis, stratum corneum hydration and stratum corneum integrity, in both mice and humans [130,131]. Besides oral administration, topical applications of some natural ingredients can also improve epidermal functions in chronologicallyaged skin.…”

The Roles of Sex Hormones in the Course of Atopic Dermatitis

“…The ovariectomy of female C57/BL6 mice reduced skin hydration, delayed skin permeability recovery after tape stripping, and reduced epidermal thickness; these were restored by the administration of E2 [80]. Ovariectomy also reduced the expression of desmoglein-1, involucrin, and loricrin, key constituents of corneodesmosome and cornified envelope (CE) in SC; these were restored by E2 treatment [80]. Ovariectomy of female nude mice (ICR-Foxn1nu) also reduced the expression of filaggrin and integrin β in the skin [81].…”

Possible involvement of type 2 cytokines in alloknesis in mouse models of menopause and dry skin

“…Dysfunction of the permeability barrier was observed at four weeks and enhanced at six weeks after ovariectomy in the Hos:HR‐1 mice without hair 3 . The barrier function of B6 mice, which are widely used to study alloknesis, after shaving hair was more vulnerable and sensitive than that of the Hos:HR‐1 mice after ovariectomy 3 . Hence, we used B6 mice four weeks after ovariectomy in this study.…”

“…Ovaries were removed through a midline skin incision, followed by flank incisions of the peritoneum, and the skin was closed with metallic clips. HRT was performed immediately after ovariectomy by the implantation of a subcutaneous, slow‐releasing E2 tablet (Innovative Research of American, Sarasota, FL) primed to release a total amount of 0.025 mg of E2 for 60 d, to maintain the serum concentration of E2 at physiologically maximal levels 3 . The experiments were approved and performed according to the guidelines of the Animal Care and Use Committee of Dokkyo University School of Medicine.…”

“…We recently reported dysfunction of the stratum corneum and enhanced irritant dermatitis in ovariectomized (OVX) mice—a model of menopause—and found that these effects were alleviated by hormone replacement treatment (HRT) with 17ß‐estradiol (E2). 3 Decreased hydration of the stratum corneum, delay in permeability barrier recovery after acute barrier disruption and weakened integrity of the stratum corneum were found in the OVX mice. This stratum corneum dysfunction could be attributed to lower levels of epidermal differentiation molecules, including loricrin and involucrin, and lower expression of desmoglein‐1, a corneodesmosome molecule.…”