Rooster feathering, androgenic alopecia, and hormone-dependent tumor growth: what is in common?

Different epithelial organs form as a result of epithelial-mesenchymal interactions and share a common theme modulated by variations (Chuong ed. In Molecular Basis of Epithelial Appendage Morphogenesis, 1998). One of the major modulators is the sex hormone pathway that acts on the prototype signaling pathway to alter organ phenotypes. Here, we focus on how the sex hormone pathway may interface with epithelia morphogenesis-related signaling pathways. We first survey these sex hormone-regulated morphogenetic processes in various epithelial organs. Sexual dimorphism of hairs and feathers has implications in sexual selection. Diseases of these pathways result in androgenic alopecia, hirsutism, henny feathering, etc. The growth and development of mammary glands, prostate glands, and external genitalia essential for reproductive function are also dependent on sex hormones. Diseases affecting these organs include congenital anomalies and hormone-dependent breast and prostate cancers. To study the role of sex hormones in new growth in the context of system biology/pathology, an in vivo model in which organ formation starts from stem cells is essential. With recent developments (Yu et al. (2002) The morphogenesis of feathers. Nature 420:308-312), the growth of tail feathers in roosters and hens has become a testable model in which experimental manipulations are possible. We show exemplary data of differences in their growth rate, proliferative cell population, and signaling molecule expression. Working hypotheses are proposed on how the sex hormone pathways may interact with growth pathways. It is now possible to test these hypotheses using the chicken model to learn fundamental mechanisms on how sex hormones affect organogenesis, epithelial organ cycling, and growth-related tumorigenesis.