Oestrogen receptor beta is the predominant oestrogen receptor in human scalp skin

Oestrogens play a major role in non-classic target tissues in both sexes, yet there have been few studies on estrogens and skin. Recently a second oestrogen receptor (ERbeta) has been discovered. Therefore, we have compared the expression of oestrogen receptor alpha (ERalpha), beta (ERbeta), the androgen receptor (AR) and a cell proliferation marker in male and female non-balding scalp skin. ERbeta was the major steroid receptor expressed in human skin. It was highly expressed in epidermis, blood vessels and dermal fibroblasts, in contrast to ERalpha and AR. In the hair follicle, ERbeta expression was localized to nuclei of outer root sheath, epithelial matrix and dermal papilla cells, in contrast to ERalpha, and the AR, which was only expressed in dermal papilla cells. Serial sections also showed strong nuclear expression of ERbeta in the cells of the bulge, while neither ERalpha nor AR was expressed. In the sebaceous gland, ERbeta was expressed in both basal and partially differentiated sebocytes. ERalpha exhibited a similar pattern of expression, while the AR was expressed in the basal and very early differentiated sebocytes. There was no obvious difference in the expression of either oestrogen receptor in male or female skin. The wide distribution of ERbeta in human skin suggests that oestrogens may play an important role in the maintenance of skin and in the regulation of the pilosebaceous unit, and provides further evidence for oestrogen action in non-classic target tissues. The differential expression of ERalpha, ERbeta and AR in human skin suggests that the mechanisms by which steroid hormones mediate their effects may be more complex than previously thought.     

Oestrogen and progesterone receptors in melanoma and nevi: an immunohistochemical study

Background

The effect of hormonal stimulation and fertility treatments, on the development of malignant melanoma (MM) remains to be determined.

Objectives

The aim of this study was to investigate the presence of oestrogen receptor alpha (ERα) and progesterone receptor (PR) inMM and nevi after hormonal stimulation.

Materials & Methods

Immunohistochemical analyses were performed utilizing antibodies specifically directed against ERα and PR in MM and atypical nevi specimens from patients: (1) diagnosed during pregnancy, (2) diagnosed in the six months following delivery, or (3) who had undergone repetitive cycles of hormonal stimulation for in vitro fertilization (IVF) in the year that preceded MM diagnosis. Controls were atypical nevi and MM specimens of female patients of the same age group who had received no hormonal therapies and reported no pregnancies in the five years before diagnosis.

Results

Twenty-eight female patients at childbearing age were selected for this study. Strong cytoplasmic positivity of ERα and PRwas detected in atypical melanocytes of two MM specimens of patients who had undergone repetitive cycles of hormonal stimulation during IVF procedures. All other specimens showed no expression ofERαor PR.

Conclusion

Since our results represent preliminary findings, conclusions regarding a possible correlation between IVF therapy and melanoma occurrence cannot be ascertained. Larger laboratory studies should be performed to investigate reproductive hormone receptor expression in MM in women following IVF, pregnancy, prolonged contraceptive use, or hormone replacement therapy.

     

How hormones may modulate human skin pigmentation in melasma: An in vitro perspective

Melasma is a common acquired hyperpigmentary disorder occurring primarily in photo‐exposed areas and mainly affecting women of childbearing age. To decipher the role of sex hormones in melasma, this viewpoint reviews the effects of sex hormones on cutaneous cells cultured in monolayers, in coculture, in 3D models and explants in the presence or the absence of UV. The data show that sex steroid hormones, especially oestrogen, can modulate in vitro pigmentation by stimulating melanocytes and keratinocyte pro‐pigmentary factors, but not via fibroblast or mast cell activation. In vitro data suggest that oestrogen acts on endothelial cell count, which may in turn increase endothelin‐1 concentrations. However, data on explants revealed that sex steroid even at doses observed during pregnancy cannot induce melanogenesis alone nor melanosome transfer but that it acts in synergy with UVB. In conclusion, we hypothesize that in predisposed persons, sex steroid hormones initiate hyperpigmentation in melasma by amplifying the effects of UV on melanogenesis via direct effects on melanocytes or indirect effects via keratinocytes and on the transfer of melanosomes. They also help to sustain hyperpigmentation by increasing the number of blood vessels and, in turn, the level of endothelin‐1.     

Tranexamic acid: an important adjuvant in the treatment of melasma

This article reviews an old drug tranexamic acid to its new use in the treatment of melasma. Its mechanism of preventing the activation of melanocyte from UV light, hormone and injured kerationcyte through the inhibition of the plasminogen activator system will be explored. The detail usage for such indication and its safety profile will also be thoroughly evaluated.     

Oestrogen receptor-beta expression in melanocytic lesions

Melanomas rarely occur before puberty, have a higher death rate for males, and tend to be more invasive during pregnancy. Prior to the discovery of a second oestrogen receptor (ERbeta), studies with the initial oestrogen receptor, ERalpha, showed no obvious role for oestrogen in the pathophysiology of benign or malignant melanocytic lesions. To investigate the specific immunostaining patterns of ERalpha and ERbeta, benign nevocytic nevi, dysplastic nevi with mild, moderate and severe cytological atypia, lentigo malignas and melanomas of varying depth (Clark) and thickness (Breslow) were studied. ERbeta but not ERalpha was the predominant oestrogen receptor we found in all types of benign and malignant melanocytic lesions. The most intense ERbeta immunostaining was seen in melanocytes in dysplastic nevi with severe cytological atypia and in lentigo malignas. ERbeta expression levels also correlated with the malignant tumor microenvironment; i.e., melanocytes in proximity with keratinocytes>deeper dermal melanocytes in contact with stroma>minimally invasive melanomas>Clark Level III/IV or thick melanomas (Breslow). Discovery that ERbeta expression varies in relation to the tumor microenvironment and increasing depth of invasion suggests its possible usefulness as a surrogate marker for neoplasia and prognosis in malignant melanoma.     

Dilated pore: a case report and an immunohistochemical study of cytokeratin expression

We report a 71-year-old Japanese female with a dilated pore in the form of a nodule above her right eyebrow. Histologic examination revealed a flask-shaped, keratinous cystic structure that was continuous with the surface epidermis and had numerous elongated rete ridges in the lower portion. An immunohistochemical study using a panel of monoclonal antibodies against cytokeratins (CKs) and involucrin detected CK1 and CK10 in the suprabasal cells of the cystic structure. CK8 and CK19 expression was observed in the outermost layer of some elongated rete ridges; it was composed of pallisading columnar cells. Most parts of the outermost layer of the cystic structure stained positively with AE1 antibody. From these immunohistochemical findings, we speculated that the dilated pore in our case was an isolated clinical entity is a follicular tumor differentiating mainly toward the infundibulum and partly toward the isthmus.     

Tranexamic acid in treatment of melasma: A comprehensive review of clinical studies

Melasma is a human melanogenesis dysfunction that results in localized, chronic acquired hyperpigmentation of the skin. It has a significant impact on appearance, causing psychosocial and emotional distress, and reducing the quality of life of the affected patients. Tranexamic acid (TA) is a plasmin inhibitor used to prevent abnormal fibrinolysis to reduce blood loss and exerts its effect by reversibly blocking lysine binding sites on plasminogen molecules, thus inhibiting plasminogen activator (PA) from converting plasminogen to plasmin. As plasminogen also exists in human epidermal basal cells and cultured human keratinocyte are known to produce PA, there is basic rationale that TA will affect keratinocyte function and interaction. A thorough literature review indicates that while TA is used through various route of administration including oral, topical, and intradermal injection and as adjutant therapy with laser to treat melasma, its efficacy is not established adequately. Further studies are needed to clarify the role of TA in treatment of melasma.     

Microneedling with glutathione versus microneedling alone in treatment of facial melasma: Split-face comparative study

Background

Melasma is a distressing disfiguring acquired pigmentary disorder especially affecting females and it is of high tendency of recurrence. Up till now, treatment of melasma is a challenging problem.

Objectives

We evaluated the effectiveness of microneedling with glutathione versus microneedling alone in treatment of melasma.

Patients and Methods

In this study, 29 adult females with epidermal type of melasma (confirmed with Wood's light examination) were enrolled. The affected area was subjected to microneedling using dermapen followed by application of glutathione solution on the right side only. This session was performed every 2 weeks for 3 months (six sessions for every patient). The response to therapy was measured using modified melasma area and severity index (m MASI) that were calculated on each side of the face (Hemi- m MASI) before treatment sessions.

Results

There was statistically significant reduction in the mean of Hemi- m MASI score over the sessions on both sides of the face but the right side (microneedling with glutathione) showed more reduction and earlier response to therapy than the left side (microneedling alone). On the left side, mean of Hemi- m MASI score before and after sessions was (4.06 ± 1.91, 2.31 ± 1.450) and on the right side, it was (4.21 ± 2.08, 1.96 ± 1.30), respectively and this was statistically significant. Percentage of improvement on the left side was 46.92 ± 16.30 (%) while on the right side was 55.17 ± 15.50 (%) and this was statistically significant.

Conclusions

Microneedling is an effective promising tool in treatment of melasma and its combination with glutathione as a whitening agent, increases and accelerates its efficacy. So, combined therapy is more preferred than monotherapy in treatment of facial melasma.     

Skin hyperpigmentation index in melasma: A complementary method to classic scoring systems

Background

Due to relapsing nature of melasma with significant impact on quality of life, an objective measurement score is warranted, especially to follow-up the patients with melasma and their therapy response in a quantitative and precise manner.

Aims

To prove concordance of skin hyperpigmentation index (SHI) with well-established scores in melasma and demonstrate its superiority regarding inter-rater reliability. Development of SHI mapping for its integration in common scores.

Methods

Calculation of SHI and common melasma scores by five dermatologists. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) and concordance by Kendall correlation coefficient.

Results

Strong concordance of SHI with melasma area and severity index (MASI)-Darkness (0.48; 95% CI: 0.32, 0.63), melasma severity index (MSI)-Pigmentation (0.45; 95% CI: 0.26, 0.61), and melasma severity scale (MSS) (0.6; 95% CI: 0.42, 0.74). Using step function for mapping SHI into pigmentation scores showed an improvement of inter-rater reliability with a difference in (ICC of 0.22 for MASI-Darkness and 0.19 for MSI-Pigmentation), leading to an excellent agreement.

Conclusion

Skin hyperpigmentation index could be an important additional cost-and time-conserving assessment method, to follow-up the patients with melasma undergoing brightening therapies in clinical studies, as well as in routine clinical practice. It is in strong concordance with well-established scores but superior regarding inter-rater reliability.     

Aggravating factors for melasma: a prospective study in 197 Tunisian patients

Background Melasma is a frequent cause of consultations at dermatology departments by dark‐skinned patients in Tunisia. Objective To investigate factors that influence melasma severity in a large Tunisian population. Methods A total of 197 patients (188 women and 9 men), who attended Tunis Military Hospital for a consultation were included prospectively from August 2005 to August 2006. Disease severity was estimated using the Melasma Area and Severity Index (MASI). Aggravating factors were investigated using multiple logistic regressions. Results Of the women included, 14% presented phototype III, 45% phototype IV and 41% phototype V; 76% presented a centrofacial melasma phenotype, 23% a malar and 1% a mandibular phenotype. About 60% developed melasma before thirty. Sun exposure was reported as a triggering factor by 51% of women and as an aggravating factor by 84%. Pregnancy was reported as an aggravating factor by 51% of women who had been pregnant, and oral contraceptive use reported by 38% of women exposed to oral contraceptives. The risk of severe melasma was about three times higher for women with age at onset under 30, phototype V and major lifetime sun exposure and about 8 times higher for women exposed to oral contraceptives. Conclusion This study identifies a number of factors associated with the severity of melasma. Further epidemiological studies in this type of population, in particular, to investigate triggering factors, are justified by the aesthetic damage caused by melasma in dark‐skinned patients, lack of efficacy of existing treatments, non‐compliance with photoprotection recommendations and the challenge of treatment.     

Differential expression of oestrogen receptor isoforms and androgen receptor in the normal vulva and vagina compared with vulval lichen sclerosus and chronic vaginitis

BACKGROUND: Although the expression of the oestrogen receptor (ER) alpha isoform and androgen receptor (AR) has been examined in vulval lichen sclerosus (VLS), the distribution pattern of ERalpha, ERbeta and AR has not been described in chronic atrophic vaginitis nor correlated with markers of proliferation (Ki-67) in either of these diseased tissues. OBJECTIVES: To measure the levels and distribution of ERalpha, ERbeta and AR immunoreactivity in relation to Ki-67 in normal and diseased vulva and vagina. METHODS: The expression of ERalpha, ERbeta and AR in relation to the proliferation marker Ki-67 in VLS, squamous hyperplasia of the vulva and chronic atrophic vaginitis was determined by immunohistomorphometric analysis and compared with that in normal vulva and vagina. RESULTS: VLS showed similar ERalpha and ERbeta expression in the 'epidermal' and 'dermal' tissue layers to that of normal vulvae, whereas AR expression appeared to be absent in most cases. ERbeta and Ki-67 expression was correlated with ERalpha expression but only in the 'fibrovascular' layer of the vulva. ERalpha expression was absent from the 'fibromuscular' layer of diseased vulvae, while ERbeta expression was absent in normal tissues but was highly expressed in diseased vulvae. ERalpha expression was significantly correlated with AR expression in the fibrovascular layer of the vagina and inversely correlated with Ki-67 staining in the parabasal cells of the epidermis in patients with chronic atrophic vaginitis. CONCLUSIONS: These data suggest that ER expression and levels may be implicated in the aetiopathology of VLS and chronic atrophic vaginitis.     

Efficiency of ellagic acid and arbutin in melasma: a randomized, prospective, open-label study

The aim of this study was to compare the effectiveness of gel formulations containing arbutin, synthetic ellagic acid and plant extracts that contain ellagic acid, on patients with melasma. Thirty patients who applied to Ege University Medical Faculty, Department of Dermatology, were included in the study. A signed consent was obtained from each patient prior to study. Patients whose type of melasma was determined via Wood's lamp were randomized to groups of arbutin, synthetic ellagic acid and plant extract containing natural ellagic acid. The pigment density of patients was evaluated via Mexameter before and after the treatment. The approval of the Institutional Ethics Committee of Ege University was obtained before the study. Wilcoxon and Kruskal-Wallis tests were used in the statistical analysis. Nine of 10 patients, for whom synthetic ellagic acid was started, completed the study. A decrease in the level of melanin was determined in eight of these nine patients (P = 0.038). A significant decrease in the level of melanin was also determined in all 10 patients who used plant extract containing ellagic acid (P = 0.05). A significant response was obtained from all of 10 patients who used arbutin. The difference between pre- and post-treatment levels of melanin was statistically significant (P = 0.05). Formulations prepared with plant extracts containing ellagic acid was found effective on melasma, similar to the formulations containing synthetic ellagic acid and arbutin. This material that is not yet being used widespread commercially on melasma could be an effective alternative for treatment of melasma.