O#28   Steroid hormones exhibit trophic effects on hair bulb melanocytes in hair follicle organ culture

Desmond J. Tobin and M. Julie Thornton. Dept of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire, England

Several studies have suggested a role for estrogens and androgens in regulating mammalian pigmentation. Some areas become hyperpigmented after puberty and during pregnancy and steroids may also be important in regulating hair and coat color. In order to establish a role for estrogens and androgens in human hair follicle melanocyte biology, we examined the effects of these hormones in an organ culture system. Hair follicles were isolated from occipital male scalp and were graded morphologically for quality and growth cycle stage. Only intact anagen VI follicles were selected to be grown in glucose supplemented William's E serum-free medium containing either vehicle (0.0001% ethanol), or 10 nM testosterone, 5a-dihydrotestosterone, 17b-estradiol, or combinations of 17b-estradiol with either testosterone or 5a-dihydrotestosterone. After 4 days hair follicles were assessed by high-resolution light microscopy and transmission electron microscopy. Results of this study indicated that most pigmented hair bulb melanocytes were lost from control hair follicles (n=4), while remaining melanocytes exhibited evidence of apoptosis. By contrast, hair follicles grown in estradiol contained many intact hair bulb and outer root sheath melanocytes. The former also exhibited their characteristic dendritic and pigmented phenotypes. Remarkably, these pigment cells were occasionally even seen to proliferate - an event that does not usually occur at this stage of the hair growth cycle (i.e. anagen VI). Hair follicles treated with 5a-dihydrotestosterone however, contained several pigmentary abnormalities including cell apoptosis, pigment clumping, and clustering of degenerating pigment cells transferred to the pre-cortex. Similar, but milder, effects were seen with testosterone. Estradiol combined with either androgen did not completely reverse these melanocyte defects. This study demonstrates that both estrogens and androgens positively influence hair follicle melanocyte homeostasis, but estrogens markedly increase cell survival. These data suggest that androgens and estrogens may be directly responsible for the increase in hair pigmentation that is associated with the vellus to terminal hair during and after puberty. Conversely, these steroid hormones may have the opposite effect in the terminal to vellus hair follicle transformation that is associated with hair miniturization during androgenetic alopecia.