The inhibitory effect of androgen and sex-hormone-binding globulin on the intracellular cAMP level and tyrosinase activity of normal human melanocytes.
The effect of androgens on human melanocytes has not been well clarified. We studied the effects of androgens on normal human melanocytes in the presence or absence of sex-hormone-binding globulin (SHBG), which complexes with those hormones. Immunohistochemically, testosterone and SHBG co-localized on the cell membrane. Androgens such as testosterone, 5alpha-dihydrotestosterone, and methyltrienolone (R1881, a potent synthetic androgen), reduced intracellular cAMP levels after treatment with SHBG, but hydrocortisone had no effect. We also found that testosterone and R1881 slightly suppressed tyrosinase activity in melanocytes when treated with SHBG, although they had no effect on the expression of tyrosinase at the transcriptional or translational level, as measured by semi-quantitative reverse transcriptase-polymerase chain reaction and by Western blot analysis, respectively. Our results suggest that androgens may modulate tyrosinase activity at the posttranslational level through the cell membrane signaling pathway.
Tadokoro
Taketsugu
T
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, MD, USA. tadokoro@derma.med.osaka-u.ac.jp
Rouzaud
Francois
F
Itami
Satoshi
S
Hearing
Vincent J
VJ
Yoshikawa
Kunihiko
K
D000728:Androgens / Q000378:metabolism*; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007150:Immunohistochemistry; D008544:Melanocytes / Q000378:metabolism*; D015741:Metribolone / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D012880:Skin Pigmentation; D013739:Testosterone / Q000096:biosynthesis / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic
D000728:Androgens; D012333:RNA, Messenger; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D015741:Metribolone; D013739:Testosterone; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase; D006854:Hydrocortisone