Evidence that activation of protein kinase A inhibits human hair follicle growth and hair fibre production in organ culture and DNA synthesis in human and mouse hair follicle organ culture.
We have investigated the possibility that protein kinase A (PKA) may play a part in regulating the activity of human and mouse hair follicles in whole organ culture. Human hair follicles were isolated from facial skin by microdissection, and hair follicle and hair fibre length measurements were made daily during suspension culture. Incubation of human hair follicles with dibutyryl-cAMP (db-cAMP) resulted in a dose-dependent inhibition of total cumulative follicle growth (IC50 = 100 mumol/L, 85% inhibition at 1 mmol/L). db-cAMP (0.5 mmol/L) also caused a rapid, partial inhibition of follicular DNA synthesis (20.3% inhibition at 6 h, 48.0% inhibition at 24 h). Human hair follicle growth was inhibited by the phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine and Ro 20-1724, and by the adenylate cyclase activator, forskolin. In addition, db-cAMP inhibited DNA synthesis in organ cultures of whisker follicles isolated from neonatal mice by microdissection. Taken together, these findings indicate that agents which increase cAMP levels are potent inhibitors of human and mouse hair follicle growth, and suggest that PKA may play a part in the regulation of hair follicle activity in vivo.
Harmon
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CS
Preclinical Dermatology Research, Hoffmann-La Roche, Nutley, NJ 07110, USA.
Nevins
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D006197:Hair / Q000254:growth & development; D018859:Hair Follicle / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009924:Organ Culture Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D014738:Vibrissae / Q000254:growth & development
D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D003994:Bucladesine; D004247:DNA; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine