MELANOGENESIS DURING THE ANAGEN-CATAGEN-TELOGEN TRANSFORMATION OF THEMURINE HAIR CYCLE

Melanin synthesis of follicular melanocytes is strictly coupled to the growth stage of the hair cycle (anagen), ceases during follicle regre ssion (catagen), and is absent throughout the resting stage (telogen). Having previously characterized the expression and activity of melano genesis-related proteins during the telogen-anagen transition of the m urine hair cycle (JID 96:172, 1991), we here report a biophysical and biochemical analysis of follicular melanogenesis during the anagen-cat agen-telogen transformation of the C57 BL-6 mouse hair cycle. Tyrosina se activity and concentration as well as dopachrome tautomerase activi ty were compared with melanin synthesis, as measured by electron param agnetic resonance spectroscopy (EPR). The visible changes in skin colo r and the histologically appreciable switch-off of melanin formation d uring the anagen-catagen transformation were accompanied by a steep de cline in 1) the melanin-associated EPR signal of full-thickness mouse skin, 2) tyrosinase and dopachrome tautomerase activities, and 3) the skin concentration of 80-85-kD melanogenesis related protein and 66-68 -kD tyrosinase protein. Telogen skin displayed a minimum of the EPR am plitude as well as of tyrosinase and dopachrome tautomerase activity d etected. By EPR, only eumelanin was identified during all hair cycle s tages. The gradual switch-off of melanogenesis during anagen VI starte d with an unexpectedly early decline of the EPR melanin signal, follow ed by dopachrome tautomerase activity and the concentration of 80-85-k D melanogenesis related protein. The initiation of catagen was charact erized by a significant and rapid decrease in activity and concentrati on of tyrosinase, and was accompanied by a second drop in dopachrome t automerase activity. Together, these biochemical and biophysical param eters of follicular melanogenesis serve as novel and differential mark ers for the imminent termination of anagen and the development of cata gen. They also show that the switch-off of melanogenesis during the an agen-catagen-telogen transition is a stochastic process commencing alr eady in mid anagen VI.