The hair cycle and its regulation

The most important feature of hair growth is the cyclic activity of hair follicles in which an active phase, anagen, is succeeded by a resting phase, telogen, during which the fully formed hair remains anchored in the follicle. Between anagen and telogen there is a short transitional phase called catagen. In 1924, Trotter¹ recognized that such a cycle existed in man. Two years later, Dry² described the cycle in detail for the mouse and first used the terminology, which currently is universally accepted. A detailed account of the hair cycle in the human scalp, however, awaited the work of Kligman in 1959.³ Today, his pictures still provide classic illustrations of the sequence of events.     

The molecular basis of hair growth

For a long time, hair follicle development could be studied on the morphological level only. Now that molecular genetics is coming of age, we are beginning to understand the molecular basis of hair follicle development. The study of inherited hair disorders and basic research have both contributed to our insights and exciting developments can be expected in the near future. Here, we present a compact overview of the essential players in hair development and propose a simple model of the genetic interactions in the hair follicle.     

血管生成素在小鼠皮肤中的表达及其对小鼠毛发生长的影响

目的:探讨血管生成素在小鼠皮肤中的表达及其对小鼠毛发生长的影响.方法:利用松香-石蜡拔毛法诱导C57BL/6小鼠背部的毛囊同步进入生长期,半定量RT-PCR检测血管生成素mRNA在不同毛囊周期小鼠皮肤中的表达.分离与培养完整的小鼠触须毛囊,加入不同浓度的血管生成素(0～200 μg/L),培养8 d 后测量毛囊的生长长度.与此同时,皮内注射血管生成素或血管生成素真核表达质粒pEGFP-ANG,并设立同时注射抗人血管生成素抗体组、注射空质粒pEGFP-C2 组和注射赋形剂的对照组,观察小鼠局部皮肤颜色的改变,并借助苏木精-伊红染色组织切片测量皮肤的厚度和计数生长期Ⅵ毛囊的比例.结果:半定量RT-PCR 显示小鼠皮肤中血管生成素mRNA 在生长期表达逐渐增加,生长期晚期表达最高,退行期开始减少,至休止期表达最低,其表达模式与毛囊周围的血管形成相一致.12.5～200.0 μg/L血管生成素呈剂量依赖性地促进体外培养的小鼠触须毛囊生长(P < 0.01).而且,皮内注射血管生成素和血管生成素真核表达质粒对C57BL/6小鼠背部的局部皮肤颜色无明显影响,但能明显增加局部皮肤的厚度(P ＜ 0.01)和生长期Ⅵ毛囊的比例(P ＜ 0.01).结论:血管生成素在小鼠皮肤中的表达具有毛囊周期依赖性的特点,血管生成素可能通过促进毛囊周围的血管形成和诱导毛囊进入生长期Ⅵ而促进小鼠毛发的生长.     

血管生成素在人毛囊中的表达及其对毛发生长的影响

目的 探讨血管生成素在人毛囊中的表达及其意义。方法 分离完整的人生长期毛囊,提取总RNA,RT-PCR法检测血管生成素mRNA的表达,同时应用免疫组化法检测血管生成素蛋白在人毛囊中的表达。在此基础上,在体外培养的人毛囊中加入不同浓度的重组人血管生成素（0 ～ 200 ng/mL）,培养6 d后测量毛囊的生长长度。利用两步酶法分离培养人毛乳头细胞,加入不同浓度的重组人血管生成素（0 ～ 200 ng/mL）,48 h后,MTT法检测细胞增殖,流式细胞仪检测细胞周期。结果 RT-PCR显示人毛囊表达血管生成素mRNA,免疫组化法发现人毛囊的毛乳头和真皮鞘表达血管生成素蛋白。25 ～ 200 ng/mL重组人血管生成素呈浓度依赖性促进体外培养的人毛囊生长（P < 0.05）,而12.5 ～ 200 ng/mL重组人血管生成素能够明显促进体外培养的人毛乳头细胞增殖（P < 0.05）。流式细胞仪检测12.5 ～ 200 ng/mL重组人血管生成素能够显著增加S期细胞比率和细胞增殖指数（P < 0.05）。结论 血管生成素可能是一种促进毛发生长的因子。     

维生素D及其受体对毛囊生长周期调控的研究进展

毛囊是体表不断自我循环的组织器官,形成于胚胎期,出生后逐渐成熟。由角质形成细胞和真皮乳头细胞组成,维生素D受体(VDR)是维持角质形成细胞正常功能的重要组成成分,开启毛囊生长周期。VDR的DNA结合区和活性功能2区在毛囊生长周期中起作用。VDR的经典转录途径是结合配体1α,25二羟维生素D_3(VD_3),与二聚化搭档维A酸X受体a(RXRa)形成异质二聚体,吸引共激活剂或者共抑制剂,作用于含有VDR反应元件启动子的基因,调节转录。VDR调节毛囊生长周期不需要VD_3,但VD_3及类似物对毛囊确有一定的作用。VDR的共抑制剂无毛基因、共激活剂MED1及二聚化配体RXRa受损都会导致毛发脱落。毛囊生理主要涉及Wnt信号通路和Shh信号通路,两条通路之间可相互作用,VDR以非经典途径调节这两条信号通路。维生素D的研究较少,VDR的具体作用机制待进一步研究。     

药物反应对毛发生长的影响

临床结果显示,许多药物反应对毛发生长有影响.该文就药物引起的脱发类型,对毛发生长产生影响的药物种类以及相关的临床表现和诊断要点作一综述.     

Effect of plant worm extract on mouse hair growth

Topical application of plant worm extract (Chinese drug, dong chong xia cao) caused a dose-dependent acceleration of hair growth on the dorsal resting hair of shaved C3H mice. The original extract, which was extracted from 3 g of plant worm with 400 ml of 75% ethanol, and a 10-fold concentrate were significantly effective in accelerating hair regrowth. Even a 100-fold diluted extract shortened the anagen time of terminal hair growth. The hair regrowth activity of the extract was also highly significant when compared with two solutions containing some other effective ingredients for hair regrowth. The extract did not show any apparent acute toxicity in the mice. No mutagenicity was detected. No systemic or local side effects attributable to the plant worm extract were evident.     

米诺地尔对培养人头皮毛囊生长的影响

通过毛囊器官培养模型及3H－TdR掺入实验观察不同浓度米诺地尔对人头皮毛囊生长的影响。结果：0．05mmol/L,0.1mol/L及0.5mmol/L米诺地尔组在加药后1－3天内毛囊平均每天生长长度和总生长长度均明显大于对照组（P＜0．01，P＜0．05），3H－TdR掺入实验救 射活性显著高于对照组，2mmol/L米诺地尔组毛囊生长速度显著受抑（P＜0．05），3个低浓度米诺地尔组毛囊组织学发生退行期改变的时间均较对照组延迟，米诺地尔在一定的浓度范围促进人头皮毛囊生长，对毛囊的正调节作用是直接的，但高浓度反而抑制毛囊生长。     

The effect of sebocytes cultured from nevus sebaceus on hair growth

Sebaceous glands are known to affect hair growth. Nevus sebaceus, a sebaceous gland hamartomas, presents as hairless patches. In this study, cultures of nevus sebaceus sebocytes (NSS) and normal scalp hair follicle sebocytes (NS) were used in performance of microarray, RT‐PCR, western blot assay and immunofluorescence staining. NSS‐ and NS‐conditioned media were also added to the culture of outer root sheath cells (ORSCs), dermal papilla cells (DPCs) or normal scalp hair follicle sebocytes. Results of this study showed a decrease in the survival rate of ORSCs and DPCs and hair growth in the NSS‐conditioned medium‐treated group, compared with the control and NS‐conditioned medium‐treated groups. An increase in expression of fibroblast growth factor (FGF)‐5, Dickkopf‐1 and inflammatory cytokines and a decrease in expression of Wnt10b and Lef1 were observed. In conclusion, NSS showed an increase in expression of hair growth‐suppressing bioactive factors, including FGF‐5, and a decrease in expression of hair growth‐stimulating factors.     

The effect of hepatocyte growth factor/scatter factor on human hair follicle growth

The effect of hepatocyte growth factor/scatter factor (HGF/SF) on human hair follicle growth was examined using a serum-free organ culture system. The DNA synthesis in human hair follicles and elongation of the hair shaft were measured subsequent to the follicle isolation and culture at 31 °C in 95% O₂-5% CO₂ for 72 h. Results showed that HGF/SF significantly increased ³H-thymidine (P < 0.001) incorporation and hair follicle length (P < 0.05). The effect of HGF/SF was dose-dependent with a maximal stimulation at 10 ng/ml.     

The control of hair growth

The hair follicle is one of a few human tissues containing stem cells. The stem cells are interspersed within the basal layer of the outer root sheath and in an area called the bulge. From this reservoir stem cells migrate to hair matrix and start to divide and differentiate. Their behavior is controlled by numerous cytokines produced by cells of the dermal papilla. Dermal papilla cells and some cells of the inner and outer sheaths of the follicle from androgen-dependent hairs have androgen receptors in their cytoplasm and nucleus. Androgens indirectly control hair growth by influencing the synthesis and release of cytokines from the dermal papilla cells. Drugs affecting hair growth belong to one of the following groups: cytotoxic drugs, antiandrogens and drugs acting on potassium channels. Further development of drugs selective for certain steps in the process of hair growth will enable more successful therapy of hair growth disorders.