title: A unique urinary constituent, 6-hydroxy-6-methyl-3-heptanone, is a pheromone that accelerates puberty in female mice.
abstract: BACKGROUND
  Olfactorily mediated puberty acceleration in female mice (measured by an increase in uterine weight) has been observed since the 1960s without the active chemosignal being structurally identified. There are many controversies in the literature as to whether this male-originated pheromone is a volatile substance. We investigated the chemical nature of the urinary fractions that are responsible for the characteristic uterine weight increases.
  
  
  RESULTS
  The active pheromone was identified as 5,5-dimethyl-2-ethyltetrahydrofuran-2-ol and/or its open-chain tautomer (6-hydroxy-6-methyl-3-heptanone). A series of cyclic vinyl ethers were isolated from chromatographically active fractions of the urine. Because these compounds did not accelerate puberty, we postulated that these ethers were degradation products of a lactol (5,5-dimethyl-2-ethyltetrahydrofuran-2-ol). The lactol was then detected directly in the mouse urine extract using a silylation agent. Synthetic 6-hydroxy-6-methyl-3-heptanone had strong biological activity, whereas its close structural analogs did not.
  
  
  CONCLUSIONS
  The male house mouse excretes into its urine a large quantity of a volatile substance that has a unique lactol/hydroxyketone structure. This substance is capable of binding to the less volatile urinary constituents, such as proteins or peptides, and is active in puberty-acceleration bioassays. The controversies regarding the volatility of the puberty-accelerating pheromones can now be explained by considering a complex of volatile lactol/hydroxyketone and urinary proteins.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, IN 47405, USA. novotny@indiana.edu
authors.forename: M V
authors.initials: MV
authors.lastname: Novotny
authors.forename: B
authors.initials: B
authors.lastname: Jemiolo
authors.forename: D
authors.initials: D
authors.lastname: Wiesler
authors.forename: W
authors.initials: W
authors.lastname: Ma
authors.forename: S
authors.initials: S
authors.lastname: Harvey
authors.forename: F
authors.initials: F
authors.lastname: Xu
authors.forename: T M
authors.initials: TM
authors.lastname: Xie
authors.forename: M
authors.initials: M
authors.lastname: Carmack
mesh_terms: D000818:Animals; D005260:Female; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology / Q000652:urine*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D010675:Pheromones / Q000737:chemistry / Q000494:pharmacology / Q000652:urine*; D012741:Sexual Maturation / Q000187:drug effects / Q000502:physiology*; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development
chemical_list: D007659:Ketones; D010675:Pheromones; C061311:6-hydroxy-6-methyl-3-heptanone