The apocrine sweat glands of the human axilla produce odor

The apocrine sweat glands of the human axilla produce odor substances with pheromone functions whose nature corresponds to volatile steroids (Cowley and Brooksbank, 1991, Grosser et al., 2000, Sobel et al., 1999, Weller, 1998). These functions only begin with puberty, indicating that sex hormones stimulation is required (Groscurth, 2002). Indeed, the presence of intranuclear and cytosolic androgen receptors in apocrine sweat glands from male and female patients with osmidrosis, has been suggested by ligand binding assays (Kurata et al., 1990). Immunohistochemistry studies demonstrated strong expression of androgen receptor (AR) and estrogen receptor-β (ER-β) in the apocrine secretor epithelium (Beier et al., 2005). AR showed a higher expression correlated to the height of epithelium (Beier et al., 2005). These results agree with the fact that the low epithelium is considered to be resting or inactive and therefore, the secretory activity would be regulated by androgen action through AR. Likewise, androgens upregulate many ep4 receptor involved in cholesterol synthesis (Swinnen et al., 1997) and given the role of cholesterol as pheromone precursor, then androgen would have an important role in the synthesis and secretion of these volatile hormones. Similarly, DHT was shown to increase the expression of Apoprotein D (Apo D) in apocrine gland cells, a protein that plays a carrier role for axillary odor molecules (Chen et al., 2011). On the other hand, it has been observed that isolated human apocrine sweat glands showed high levels of 5α-reductase activity (Hay and Hodgins, 1978, Takayasu et al., 1980, Barth and Kealey, 1991) and a higher concentration of DHT than testosterone in axillary skin from patients suffering from osmidrosis (Kurata et al., 1990). These results suggested an anabolic activity of 5α-reductase in apocrine sweat glands as it happens in sebaceous glands, supported by the fact of the predominance of 5α-reductase type 1 in this kind of glands (Sato et al., 1998). The regulatory roles of androgens and estrogens in skin wound healing were already extensively reviewed (Fimmel and Zouboulis, 2005, Gilliver et al., 2003). Androgen receptor (AR) is expressed in keratinocytes, inflammatory cells (mainly macrophages) and fibroblasts involved in the wound healing process in C57BL/6 wild type male mice (Ashcroft and Mills, 2002). This expression of AR during early wound healing associated both to epithelization and inflammatory cellular infiltrate, would involve this receptor in inflammation and/or repair processes. Castration of these animals resulted in more rapid cutaneous wound healing associated to a reduced inflammatory response, as it was pointed out by the reduction of TNF-α expression in the wounded tissue. Therefore, endogenous testosterone could be inhibiting wound healing by upregulating proinflammatory cytokines secreted by macrophages. Similar results were observed with flutamide treatment in non-castrated animals (Ashcroft and Mills, 2002). In addition to the effects on skin wound healing, androgens also demonstrated to play a role in cutaneous barrier formation (Hanley et al., 1996). Transepidermal water loss, as indicator of impaired barrier formation, was higher in male than female fetal rats and the administration of the estrogen diethylstilbestrol to pregnant mothers at estimated gestational day 14–16 accelerated fetal skin barrier development both morphologically and functionally. Otherwise dihydrotestosterone (DHT) delayed barrier fetal development when it was administered to pregnant mothers. Finally, the administration of AR antagonist flutamide in the same in vivo model avoided gender differences in barrier formation. The effects of androgen on barrier homeostasis in both adult murine and human skin (Kao et al., 2001) were similar to what was exposed for fetal barrier formation. Hypogonadal mice showed faster skin barrier retrieval than normal animals and their treatment with testosterone displayed similar values to control. Similar results were observed in human hypopituitary patients treated with testosterone. The androgen mechanism underlying this effect appears to be related to epidermal lamellar body formation rather than to differences in lipid synthesis (Kao et al., 2001).