Tang Liren, Bernardo Olga, Bolduc Chantal, Lui Harvey, Madani Shabnam, Shapiro Jerry
Division of Dermatology, The University of British Columbia, Vancouver Hospital, Canada.
J Am Acad Dermatol. 2003 Aug;49(2):229-33. doi: 10.1067/s0190-9622(03)00777-1.
It is generally believed that dihydrotestosterone is one of the pivotal mediators of hair loss in androgenetic alopecia (AGA). Finasteride, which blocks the conversion of testosterone to dihydrotestosterone, has now become an integral part of the current treatment approaches for male AGA. Several lines of evidence support the notion that dermal papilla (DP) cells represent the androgen target within the hair follicle. The specific molecular regulators modulated by androgens within hair follicles in the balding scalp are unknown.
The purpose of this study was to identify and quantify changes in expression of specific molecular hair growth regulators in DP of men with AGA treated with finasteride and correlate these findings to clinical efficacy.
Biopsy specimens were collected from 9 male patients from both the balding area and nonbalding occipital area before and after 4 months of finasteride therapy. DP were microdissected and total RNA was extracted from an equal number of DP from each biopsy specimen. The expression of various cytokines, including insulin-like growth factor (IGF)-1, was determined by reverse transcription polymerase chain reaction. The signals were detected by autoradiography. All 9 patients were given finasteride for 1 year and evaluated for efficacy at month 12. Efficacy was graded on a 7-point scale on the basis of comparison with initial baseline photography.
IGF-1 was up-regulated by finasteride treatment in 4 of 9 patients. Among the patients with increased IGF-1 expression, 3 of them showed moderate clinical improvement after 12 months of treatment and another patient remained unchanged. In contrast, 3 patients with decreased IGF-1 expression in the balding scalp showed clinical worsening after 12 months. The other 2 patients without noticeable change in IGF-1 expression showed either slight improvement or no change in their hair condition.
In a small uncontrolled study of 9 patients with AGA, an increased expression of IGF-1 messenger RNA levels in the DP was associated with patient response to finasteride.
一般认为，双氢睾酮是雄激素性脱发（AGA）中脱发的关键介质之一。非那雄胺可阻止睾酮转化为双氢睾酮，现已成为当前男性AGA治疗方法的重要组成部分。有几条证据支持这样的观点，即毛乳头（DP）细胞是毛囊内的雄激素作用靶点。雄激素在秃发头皮毛囊内调节的特定分子调节因子尚不清楚。
本研究的目的是识别和量化接受非那雄胺治疗的AGA男性患者DP中特定分子毛发生长调节因子表达的变化，并将这些发现与临床疗效相关联。
在非那雄胺治疗4个月前后，从9名男性患者的秃发区和非秃发枕部区域采集活检标本。对DP进行显微切割，并从每个活检标本中数量相等的DP中提取总RNA。通过逆转录聚合酶链反应测定包括胰岛素样生长因子（IGF）-1在内的各种细胞因子的表达。通过放射自显影检测信号。所有9名患者均接受非那雄胺治疗1年，并在第12个月评估疗效。根据与初始基线照片的比较，疗效采用7分制评分。
9名患者中有4名患者经非那雄胺治疗后IGF-1上调。在IGF-1表达增加的患者中，其中3名在治疗12个月后显示出中度临床改善，另一名患者无变化。相比之下，3名秃发头皮中IGF-1表达降低的患者在12个月后临床症状恶化。另外2名IGF-1表达无明显变化的患者头发状况略有改善或无变化。
在一项对9名AGA患者的小型非对照研究中，DP中IGF-1信使RNA水平升高与患者对非那雄胺的反应相关。
