17.    Variable proliferative and melanogenic effects of oestradiol and selective oestrogen receptor agonists in human hair follicle melanocytes and melanoma in vitro.
Aisha Meskiri, M Julie Thornton, Sobia Kauser, Desmond Tobin Medical Biosciences Research Group, School of Life Sciences, University of Bradford, Bradford, UK

It has long been noted that cutaneous pigmentation can alter during pregnancy and resolve following parturition. Epidemiological studies on malignant melanoma suggest that females may have survival advantage. Moreover, hair color may darken significantly in fair-haired females after puberty. However, despite these clinical observations the role of estrogens in melanocytic cell biology remains unclear. In this study we examined the effects of estradiol, and agonists selective for estrogen receptor (ER)-alpha and ER-beta on primary hair follicle melanocytes (HFM) and on melanoma cells with moderate pigmentation (FM55) at concentrations of 10-7, 10-8 and 10-9 M. Cells were serum-starved for 24h, and replenished with 10% stripped serum (steroid-free) plus estradiol or the ER agonists for 72h. The cells were photo-documented for effects on morphology, trypsinized and counted using a hemocytometer, then pelleted for photo-documentation and melanin measurement (@ 490 nm). Estradiol and selective agonists to ER-alpha and ER-beta reduced HFM proliferation, although little effect was detected morphologically. By contrast, these agents induced a mild to moderate increase in HFM melanin levels. Estradiol and the ER-alpha and ER-beta selective agonists moderately upregulated proliferation in FM55 melanoma, again with little effect detected morphologically. As with HFM, estradiol and selective agonists to ER-alpha and ER-beta induced a mild to moderate increase in FM55 melanoma pigment levels. These results suggest that estrogens have a similar melanogenic effect on both HFM and FM55 melanoma cells, but these melanocytic cells types exhibit opposite proliferation responses. In summary, these preliminary findings suggest that HFM pigmentation may be regulated by estrogens acting via ER-beta and ER-alpha. Agonists at these receptors may also be implicated in regulating cell proliferation differentially in normal (eg. HFM) and transformed melanocytic cells (melanoma).