SFE2005 Poster Presentations Steroids to include Cushing's (15 abstracts)
Dept. Biomedical Sciences, University of Bradford, Bradford, United Kingdom.
An increase in cutaneous pigmentation during pregnancy is common, but usually regresses following parturition. Epidemiological studies also suggest that females may have a sex survival advantage in cases of malignant melanoma. However, estrogen action in melanoma remains contradictory. We have recently demonstrated that both epidermal and hair follicle melanocytes express ERα and ERβ however, estrogen action in human pigment cell biology remains poorly characterised.
This study was designed to assess whether the expression of ERα, ERβ, the androgen receptor (AR) and aromatase varied as a function of pigment level in the weakly pigmented (FM55) melanoma cell line and in normal epidermal melanocytes derived from female scalp skin. Stimulation of pigment cell differentiation was achieved by increasing cAMP (and cGMP) levels via incubation with the phosophodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) at 10−4M. Aromatase and steroid hormone receptor expression was assessed by immunocytochemistry.
The induction of pigmentation in the weakly pigmented FM55 melanoma cell line resulted in a marked increase in ERα, ERβ, AR and aromatase expression, while the induction of pigmentation in normal epidermal melanocytes resulted only in an increase in the expression of ERα and aromatase.
These findings suggest that melanogenesis may be regulated via the local synthesis of estrogens acting via ERα in normal epidermal melanocytes. The additional up regulation of AR and ERβ in melanoma cells may reflect their abnormal signalling and cellular responses. Further studies using ERα and ERβ selective ligands may help to elucidate the mechanisms of estrogen signalling in pigment cell biology.