The characteristic human axillary odor is formed by bacterial action on odor precursors that originate from apocrine sweat glands. Caucasians and Africans possess a strong axillary odor ,whereas many Asians have only a faint acidic odor. In this study, we provide evidence that the gene ABCC11 (MRP8), which encodes an apical efflux pump, is crucial for the formation of the characteristic axillary odor and that a single-nucleotide polymorphism (SNP) 538G --> A, which is prominent among Asian people, leads to a nearly complete loss of the typical odor components in axillary sweat. The secretion of amino-acid conjugates of human-specific odorants is abolished in homozygotic carriers of the SNP, and steroidal odorants and their putative precursors are significantly reduced. Moreover, we show that ABCC11 is expressed and localized in apocrine sweat glands. These data point to a key function of ABCC11 in the secretion of odorants and their precursors from apocrine sweat glands. SNP 538G --> A, which also determines human earwax type, is present on an extended haplotype, which has reached >95% frequency in certain populations in recent human evolution. A strong positive selection in mate choice for low-odorant partners with a dysfunctional ABCC11 gene seems a plausible explanation for this striking frequency of a loss-of-function allele.
We have previously shown that precursors of odorous components characteristic of axillary sweat are hardly detectable or undetectable in individuals carrying the 538G > A SNP in the ABCC11 transporter gene. However, it is unclear, whether ABCC11 is directly involved in the transport of these compounds. To approach this question, transport of peptide-conjugated potential precursors of 3-methyl-3-sulfanylhexanol (3M3SH), a key determinant of axillary malodour, was measured using membrane vesicles of Sf9 insect cells overexpressing human ABCC11. Whilst no ABCC11-mediated transport was detected for the dipeptide precursor Cys-Gly-3M3SH, the glutathione conjugate of 3M3SH (SG-3M3SH) was robustly taken up by ABCC11 at a transport rate of 0.47 pmol/mg/min. Collectively, these results illuminate SG-3M3SH as a putative precursor of 3M3SH, which then may undergo intra-vesicular maturation to generate Cys-Gly-3M3SH. Critically, the apocrine sweat gland was demonstrated to express γ-glutamyl transferase 1 (GGT1) protein, which is known to catalyse the deglutamylation of glutathionyl conjugates. Additionally, we provide evidence that recombinant and isolated hepatic human GGT1 is capable of transforming SG-3M3SH to Cys-Gly-3M3SH in vitro. To sum up, we demonstrate that the functionality of ABCC11 is likely to play an important role in the generation of axillary malodour. Furthermore, we identify GGT1 as a key enzyme involved in the biosynthesis of Cys-Gly-3M3SH.
Mouse models show that experimental stress mimicking prolonged life-stress exposure enhances neurogenic inflammation, induces adaptive immunity cytokine-imbalance characterized by a shift to Type 1 T-helper cell cytokines and increases apoptosis of epithelial cells. This affects hair growth in otherwise healthy animals. In this study, we investigate whether a prolonged naturalistic life-stress exposure affects cytokine balance and hair parameters in healthy humans. 33 (18 exam, 15 comparison) female medical students with comparable sociobiological status were analyzed during a stressful final examination period, at three points in time (T) 12 weeks apart. T1 was before start of the learning period, T2 between the three-day written exam and an oral examination, and T3 after a 12 week rest and recovery from the stress of the examination period. Assessments included: self-reported distress and coping strategies (Perceived Stress Questionnaire [PSQ], Trier Inventory for the Assessment of Chronic Stress [TICS]), COPE), cytokines in supernatants of stimulated peripheral blood mononucleocytes (PBMCs), and trichogram (hair cycle and pigmentation analysis). Comparison between students participating in the final medical exam at T2 and non-exam students, revealed significantly higher stress perception in exam students. Time-wise comparison revealed that stress level, TH1/TH2 cytokine balance and hair parameters changed significantly from T1 to T2 in the exam group, but not the control. However, no group differences were found for cytokine balance or hair parameters at T2. The study concludes that in humans, naturalistic stress, as perceived during participation in a major medical exam, has the potential to shift the immune response to TH1 and transiently hamper hair growth, but these changes stay within a physiological range. Findings are instructive for patients suffering from hair loss in times of high stress. Replication in larger and more diverse sample populations is required, to assess suitability of trichogram analysis as biological outcome for stress studies.
Emotional sweating and malodour production represent a relevant challenge to today's antiperspirant (AP) and deodorant products as stress in everyday life increases continuously. The aim of this study was to investigate stress-induced sweating in teenagers who are known to experience various stressful situations, e.g. exams at school or job interviews. To induce emotional sweating in 20 female and 20 male adolescents (16-18 years of age), we applied the Trier Social Stress Test (TSST), considered today to be the most reliable and standardized stress protocol. In this study, we demonstrate that the TSST induces high amounts of sweat and strong axillary malodour in the tested age group. Notably, male teenagers showed significantly higher stress-induced odour scores than female subjects, although no gender differences were detected concerning other physiological stress markers. Testing of a novel deodorant/AP product developed to specifically address the needs of adolescent consumers revealed excellent deodorant and AP efficacy under the challenging conditions of the TSST.
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