Harmon C S, Nevins T D
Preclinical Dermatology Research, Hoffmann-La Roche, Nutley, NJ 07110, USA.
Br J Dermatol. 1997 Jun;136(6):853-8.
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.
我们研究了蛋白激酶A(PKA)在全器官培养中可能参与调节人和小鼠毛囊活性的可能性。通过显微切割从面部皮肤分离出人毛囊,并在悬浮培养期间每天测量毛囊和毛纤维长度。用人毛囊与二丁酰环磷腺苷(db-cAMP)孵育导致总累积毛囊生长受到剂量依赖性抑制(IC50 = 100 μmol/L,1 mmol/L时抑制率为85%)。db-cAMP(0.5 mmol/L)还导致毛囊DNA合成迅速受到部分抑制(6小时时抑制率为20.3%,24小时时抑制率为48.0%)。人毛囊生长受到磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤和Ro 20-1724以及腺苷酸环化酶激活剂福斯高林的抑制。此外,db-cAMP抑制了通过显微切割从新生小鼠分离的须毛囊器官培养中的DNA合成。综上所述,这些发现表明,增加cAMP水平的试剂是人和小鼠毛囊生长的有效抑制剂,并提示PKA可能在体内毛囊活性调节中发挥作用。