**Androgenic Alopecia: Cross-Talk Between Cell Signal Transduction Pathways** Androgenic Alopecia: Cross-Talk Between Cell Signal Transduction Pathways

Anastasia Nesterova and Anton Yuryev

Additional information is available at the end of the chapter Anastasia Nesterova and Anton Yuryev Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/67845

#### Abstract

Signaling pathways that control coordination of hair follicle cells genetic program are the convenient model for explaining the hierarchy of intercellular interactions governing cyclic growth of hair. This chapter describes models of molecular signaling pathways specific to dermal papilla cells from balding human scalp in hair follicle cycle. These models include already published data, as well as information inferred from pathway analysis of microarray data and protein-protein interaction database. Interplay of androgenic-alopecia-related signaling pathways FGF, TGFB, BMP, and WNT, as well as cyclin-dependent kinases signaling, is shown.

Keywords: hair follicle, dermal papilla, catagen, androgen receptor, alopecia, microarray, pathway analysis, SNEA

### 1. Introduction

Androgenetic alopecia (AGA) is the state of progressive cessation of hair growth on the human frontal area of the scalp, most likely inherited and androgen-dependent (OMIM locus numbers are 109200, 612421, 300710). In women, as well as in men with androgenic alopecia, the growth of frontal scalp hairs slows down, and the transition occurs from terminal (pigmented and thick) hair type to vellus (nonpigmented and thin) hair type. The duration of fast growth periods (anagen) gradually reduces with each hair cycle, hair follicles become narrower and shorter, and progressively miniaturized [1]. Peak of the disease in most male patients occurs at the age of 40–50 years. Male pattern hair loss ultimately leaves narrow bands of hair on temples and occiput, where hair never fall off during AGA [2, 3].

It was thought that AGA is associated with high levels of androgens circulating in blood. However, currently prevalent firm opinion is that it is not increased levels of androgens cause

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this disease, but rather altered androgen cell sensitivity [4]. There is evidence that in AGA, in dermal papilla cells of hair follicles from the frontal and parietal scalp skin, 5a-reductase-driven synthesis of topical androgens is increased just as well as activation of androgen receptor complex [5]. The paradoxical situation occurs with accepting the androgen-dependent paradigm of AGA: when the activity of androgen-related signaling stimulates beard growth, while the same signaling arrests hair growth from frontal area of the scalp [5–8].

Nevertheless, failures in treatment of AGA using anti-androgens or 5a-reductase blockers suggest that additional causative factors do take part in the development of the disease. Present day search for beginnings of AGA is in fact search for answers to the following questions: (a) To which extent do cell-specific signaling pathways contribute to the initiation and maintenance of hair growth cessation in a frontal scalp skin? (b) What are the features of hair follicles from a beard or an occipital scalp and from a frontal scalp that manage baldness in first two cases and hair growth in another? One of the accepted answers is that despite great variety of causes, the basic mechanism of hair growth pathologies consists in discoordination of cross-talk between canonical signaling pathways within hair follicle dermal papilla and hair follicle outer root sheath stem cells [9, 10].

Signaling pathways are the convenient model for explaining the hierarchy of intercellular proteins interactions, which control the hair follicle cells genetic destiny. The pathway models described in the chapter include specific to cells of hair follicle already published data, as well as information inferred from publicly available results of microarray essays and ResNet® Mammalian database [11].
