5α‐Androst‐16‐en‐3α‐ol β‐D‐Glucuronide, Precursor of 5α‐Androst‐16‐en‐3α‐ol in Human Sweat

Abstract

5α-Androst-16-en-3α-ol (α-androstenol) is an important contributor to human axilla sweat odor. It is assumed that α-andostenol is excreted from the apocrine glands via a H2 O-soluble conjugate, and this precursor was formally characterized in this study for the first time in human sweat. The possible H2 O-soluble precursors, sulfate and glucuronide derivatives, were synthesized as analytical standards, i.e., α-androstenol, β-androstenol sulfates, 5α-androsta-5,16-dien-3β-ol (β-androstadienol) sulfate, α-androstenol β-glucuronide, α-androstenol α-glucuronide, β-androstadienol β-glucuronide, and α-androstenol β-glucuronide furanose. The occurrence of α-androstenol β-glucuronide was established by ultra performance liquid chromatography (UPLC)/MS (heated electrospray ionization (HESI)) in negative-ion mode in pooled human sweat, containing eccrine and apocrine secretions and collected from 25 female and 24 male underarms. Its concentration was of 79 ng/ml in female secretions and 241 ng/ml in male secretions. The release of α-androstenol was observed after incubation of the sterile human sweat or α-androstenol β-glucuronide with a commercial glucuronidase enzyme, the urine-isolated bacteria Streptococcus agalactiae, and the skin bacteria Staphylococcus warneri DSM 20316, Staphylococcus haemolyticus DSM 20263, and Propionibacterium acnes ATCC 6919, reported to have β-glucuronidase activities. We demonstrated that if α- and β-androstenols and androstadienol sulfates were present in human sweat, their concentrations would be too low to be considered as potential precursors of malodors; therefore, the H2 O-soluble precursor of α-androstenol in apocrine secretion should be a β-glucuronide.

The specific biochemistry of human axilla odour formation viewed in an evolutionary context

“…B 375: 20190269 array of minor acids, are linked to a glutamine (Gln) residue [10,11]. The sulfur compounds are secreted as part of a cysteine-glycine (Cys-Gly) dipeptide [20], and the steroid 5-α-androst-16-en-3α-ol was detected as a glucuronide conjugate in axilla secretions [21]. Such conjugates are well known from liver metabolism and toxicology: many acids are conjugated to Gln prior to secretion in the kidney, electrophilic chemicals are conjugated to glutathione and then secreted as Cys or Cys-Gly conjugates and many alcohols are linked to glucuronic acid to render them hydrophilic prior to secretion (e.g.…”

Mapping axillary microbiota responsible for body odours using a culture-independent approach

“…Recent studies have demonstrated that some soluble odourless compounds are secreted by apocrine glands and some are unique to the human species [ 25 ]. These soluble compounds are transformed by the microbiota to release odorant carboxylic acids, sulfur compounds and odorant steroids [ 20 - 22 , 26 ].…”

Metabolomic Analysis of Skin Malodor-Associated Compounds and Structure-based Prediction of Acetolactate Synthase Selective Sulfonylurea Inhibitors

“…Besides fermentation, odor molecules in the secondary metabolites can be produced via the gene activation or secretion systems of various microorganisms in the skin. Both C. acnes and S. warneri have the β-glucuronidase activities to increase androstenol (5alpha-Androst-16en-3alpha-ol) in sweat odors (21). Corynebacterium spp.…”

“…Previous studies have demonstrated that Corynebacterium spp. can produce VFAs, HMHA, 3M2H, and 5α-androst-16-en-3α-ol (21,33,36). Anaerococcus spp.…”