Human phermone polypeptide - Patent 20030049726
"Title:
Human phermone polypeptide
Document Type and Number:
United States Patent 20030049726
Kind Code:
A1
Link to this page:
Human phermone polypeptide - Patent 20030049726
Abstract:
Human phermones may be used to alleviate anxiety, promote beneficial moods, and to alter hypothalamic functions, such as satiety, energy balance, and reproductive biology. The present invention provides a new human pheromone polypeptide, designated “ZHMUP-2.”
Inventors:
Holloway, James L. (Seattle, WA, US)
Lok, Si (Seattle, WA, US)
Application Number:
947969
Filing Date:
09/06/2001
Publication Date:
03/13/2003
…The inconsistent findings may be due to different forms or formulation of the 16-androstenes used, or due to the subjectivity and the difficulties associated with human behavioral studies.
[0020] An alternative explanation is that a more robust reproducible human pheromone response to the androstrenes or other potential small chemical pheromones such as the estrenes (U.S. Pat. Nos. 5,272,134, 5,278,141, and 5,994,568) may require the presence of a human lipocalin carrier protein. Such a protein carrier may by itself possess phermone activity, as in the case for the murine MUPs and hamster aphrodisin. Alternatively, the carrier protein may function indirectly by augmenting, stabilizing, or effecting the sustained release of phermone ligand. In addition to hamster aphrodisin and the rodent MUP, there have only been a few examples of characterized proteins associated with pheromones in mammals and none so far in humans. Booth and White reported a partially characterized porcine extracellular protein, pheromaxein, that binds androstenol and related steroids in boar submaxillary gland saliva (Booth and White, J. Endrocr. 118:47 (1988)). A salivary gland lipocalin, which binds 16-androstrenes, was later isolated from boar submaxillary gland (Marchese et al., Eur. J. Biochem. 252:563 (1998)). A cDNA encoding this protein, termed sex-specific salivary lipocalin (SAL), was recently reported, and shown to encode a polypeptide with high homology to the murine MUPs (Loebel et al., Biochem. J. 350:369 (2000)). It is not known whether boar SAL or pheromaxein has phermone activity itself, or only contributes to the phermone activity of cognate androstene ligands. Human homologs of boar pheromaxein or SAL have not been characterized. However, a human lipocalin, apolipoprotein D, was recently found expressed in apocrine glands, and was shown to bind the axillary odorant, E-3-methyl-2-hexenoic acid (E-3M2H) (Zeng et al., Proc. Nat’l Acad. Sci. (USA) 93:6626 (1996)). E-3M2H and its isomers are major ordorants in the human axillary region. Studies have implicated axillary odors and secretions from both male and female in alterations of menstral cycle (McClintock, Nature 291:244 (1971); Stem and McClintock, Nature 392:177 (1998)). Moreover, mood changes have been reported by human volunteers exposed to donor underarm odorants (Chen and Haviland-Jones, Physiology & Behavior 68:241 (1999)). Whether E-3M2H or apolipoprotein D are involved in these responses have yet to be determined.
[0021] Hence, there is an unfulfilled need for the identification of human phermones and agents, which can augment the phermone response. Such a response may be useful for the alleviation of anxiety, promotion of beneficial moods, sexual communication, and for the alteration of hypothalamic functions, such as satiety, energy balance, and reproductive biology.
BRIEF SUMMARY OF THE INVENTION
[0022] The present invention provides a novel human phermone protein, designated “ZHMUP-2,” which is a member of the lipocalin family, and structurally related to murine major urinary proteins and porcine sex-specific salivary lipocalin. The present invention also provides ZHMUP-2 variant polypeptides and ZHMUP-2 fusion proteins, as well as nucleic acid molecules encoding such polypeptides and proteins, and methods for using these nucleic acid molecules and amino acid sequences…"