Sex steroids influence the storing of fat, and differences in the distribution of fat are a typical secondary sexual characteristic. Androgens act on fatty tissues in males either directly through stimulation of the androgen receptor or indirectly through aromatization of the estrogen receptor. Androgens can be classified as aromatizable or non-aromatizable. Testosterone (T) is the main aromatizable androgen, while its metabolite dihydrotestosterone (DHT) is a non-aromatizable androgen that acts only through the androgen receptor. It is precisely this difference in having activity only through the androgen receptor that has given rise to the hypothesis concerning the differing effects of DHT and T on body composition, with DHT possibly being responsible for male-type fat distribution. As part of my post-graduate studies we analyzed the dependence serum levels of T and DHT on age, as well as changes in their ratio with age. Further, we sought relationships between aromatizable and non-aromatizable androgens and metabolic and anthropometric parameters. We also focused on following any changes in steroidogenesis in obese males. We showed that before puberty the dominant androgen is rather DHT than T, that the fDHT/fT ratio during the life of adult males is constant, and that there is no evidence of a reversal...

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No / BACKGROUND: Androgenetic alopecia, or male pattern baldness, is a common, progressive disorder where large, terminal scalp hairs are gradually replaced by smaller hairs in precise patterns until only tiny vellus hairs remain. This balding can cause a marked reduction in the quality of life. Although these changes are driven by androgens, most molecular mechanisms are unknown, limiting available treatments. The mesenchyme-derived dermal papilla at the base of the mainly epithelial hair follicle controls the type of hair produced and is probably the site through which androgens act on follicle cells by altering the regulatory paracrine factors produced by dermal papilla cells. During changes in hair size the relationship between the hair and dermal papilla size remains constant, with alterations in both dermal papilla volume and cell number. This suggests that alterations within the dermal papilla itself play a key role in altering hair size in response to androgens. Cultured dermal papilla cells offer a useful model system to investigate this as they promote new hair growth in vivo, retain characteristics in vitro which reflect their parent follicle's response to androgens in vivo and secrete mitogenic factors for dermal papilla cells and keratinocytes. OBJECTIVES: To investigate whether cultured dermal papilla cells from balding follicles secrete altered amounts/types of mitogenic factors for dermal papilla cells than those from larger, normal follicles. We also aimed to determine whether rodent cells would recognize mitogenic signals from human cells in vitro and whether factors produced by balding dermal papilla cells could alter the start of a new mouse hair cycle in vivo. METHODS: Dermal papilla cells were cultured from normal, balding and almost clinically normal areas of balding scalps and their ability to produce mitogenic factors compared using both human and rat whisker dermal papilla cells as in vitro targets and mouse hair growth in vivo. RESULTS: Normal scalp cells produced soluble factors which stimulated the growth of both human scalp and rat whisker dermal papilla cells in vitro, demonstrating dose-responsive mitogenic capability across species. Although balding cells stimulated some growth, this was much reduced and they also secreted inhibitory factor(s). Balding cell media also delayed new hair growth when injected into mice. CONCLUSIONS: Human balding dermal papilla cells secrete inhibitory factors which affect the growth of both human and rodent dermal papilla cells and factors which delay the onset of anagen in mice in vivo. These inhibitory factor(s) probably cause the formation of smaller dermal papillae and smaller hairs in male pattern baldness. Identification of such factor(s) could lead to novel therapeutic approaches.

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