Acta Dermato-Venereologica 98-9CompleteContent | Page 12

867 INVESTIGATIVE REPORT Overexpression of Androgen, Oestrogen and Progesterone Receptors in Skin Lesions of Becker’s Naevus Ping SHENG # , Yun-Long CHENG # , Chuan-Chuan CAI # , Ya-Yun WU, Ge SHI, Ying ZHOU and Yi-Ming FAN Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China # These authors contributed equally to this study. Becker’s naevus is androgen-dependent. The aim of this study was to investigate whether oestrogen and progesterone receptors are involved in this disorder. Immunohistochemistry showed that epidermal ex- pression of androgen receptors, oestrogen receptors (α, β) and progesterone receptors was higher in skin lesions of Becker’s naevus than in perilesional and control skin. Androgen receptor overexpression was observed in pilosebaceous glands, while oestrogen and progesterone receptor overexpression was seen in hair follicles, but not in sebaceous glands in skin lesions compared with perilesional skin. Reverse tran­ scription PCR and Western blot revealed that levels of androgen, oestrogen and progesterone receptors were generally upregulated in skin lesions compared with perilesional and control skin, and their expression was usually higher in perilesional than in control skin. The- se results suggest that simultaneous overexpression of androgen, oestrogen and progesterone receptors might be implicated in the pathogenesis of Becker’s naevus. Key words: Becker’s naevus; androgen; oestrogen; progeste- rone; receptor. Accept Jun 5, 2018; Epub ahead of print Jun 8, 2018 Acta Derm Venereol 2018; 98: 867–872. Corr: Yi-Ming Fan, Department of Dermatology, Affiliated Hospital of Gu- angdong Medical University, No. 57, Renmin Avenue, Xiashan district, Zhanjiang, Guangdong, 524001, China. E-mail: [email protected] B ecker’s naevus (BN) is a fairly common dermatosis that generally becomes apparent in adolescence. It typically presents as a brown patch on the shoulder girdle and upper chest, often concomitant with hypertrichosis. The main pathological features of BN include acantho- sis, basal hyperpigmentation, and rete ridge fusion and elongation (1, 2). The aetiopathogenesis of BN is unclear. BN may represent a paradominant trait, but Cai et al. (3) proposed that mutations in ACTB might interfere with the development of hair follicles and pilar muscles development through enhanced Hedgehog signalling. Sex hormones play important roles in physiological and pathological processes in human skin. Androgen, oestrogen and progesterone mediate the biological ac- tions through their receptors. Androgen receptor (AR), oestrogen receptor (ER) and progesterone receptor (PR) belong to class I members of nuclear receptor superfami- SIGNIFICANCE Becker’s naevus is an androgen-dependent hyperpigmen- tation dermatosis occurring mostly in male teenagers. This study reveals that levels of androgen, oestrogen and pro- gesterone receptors are remarkably higher in skin lesions of Becker’s naevus compared with perilesional and control skin, using immunohistochemistry, reverse transcription PCR and Western blot. The abnormal activities of these sex hormone receptors are also present in perilesional normal- appearing skin. These results suggest that simultaneous overexpression of androgen, oestrogen and progestero- ne receptors might be implicated in the pathogenesis of Becker’s naevus. ly and serve as ligand-inducible transcription factors (4, 5). Both testosterone and dihydrotestosterone bind to AR, with a potent biological activity of dihydrotestosterone (4). ER comprises 2 isoforms, ERα and ERβ, coded by ESR1 and ESR2 genes, respectively (5); 17β-oestradiol has a similar affinity for ERα and ERβ (6). PR includes truncated PRA and full-length PRB, produced by the same PR gene (7). Androgen can influence hair growth, sebaceous gland growth and differentiation, epidermal barrier homeostasis and wound healing, while oestrogen is involved in skin ageing and cancer, pigmentation, hair growth and sebum production (8). In contrast, less is known about the impact of progesterone on skin and its appendages. Progesterone stimulates keratinocyte and sebum secretion, but inhibits pigment production and collagen degradation (9, 10). It is generally accepted that BN is an androgen-depen- dent dermatosis (11, 12). Although the true prevalence of BN in females is undetermined, BN has been shown to be more common in male teenagers with higher serum levels of androgen (11). Several reports have found AR overexpression in BN lesions (11–15). Oral spirono- lactone (50 mg/day) enlarged the hypoplastic breast in BN syndrome (16), while topical 4% flutamide solution alleviated hyperpigmentation in BN (17). These results support the role of androgen in the pathogenesis of BN. However, to date, ER and PR expression in BN is unknown. This study investigated the expression of AR, ERα, ERβ and PR in BN lesional skin using immunohi- stochemistry, reverse transcription PCR (RT-PCR) and Western blot (WB). This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340/00015555-2986 Acta Derm Venereol 2018; 98: 867–872