Dual capacity of a human olfactory receptor

Certain mammalian olfactory receptor (OR) genes are exclusively or predominantly expressed in spermatozoa [1–2]. One of these receptors, hOR17-4, has been shown to mediate directed chemotactic movement of human sperm in vitro [3]. Whether sperm ORs additionally perform their ‘conventional’ task in olfaction is a longstanding question. Here, we investigate the function of hOR17-4 in human olfaction adopting a molecular, electrophysiological and psychophysical approach. Our results support a model in which the same human OR protein is similarly utilized to fulfil chemosensory functions in such diverse cell types as spermatozoa and olfactory sensory neurons. Nasal expression of the ‘sperm’ olfactory receptor hOR17-4 was demonstrated by RT-PCR on human olfactory mucosa cDNA (Figure 1). We identified and mapped distinct exons located upstream of the coding sequence (Fig. 1C) initially postulated by means of bioinformatic analyses. Such upstream exons have been described for a number of human and murine olfactory receptor genes [4]. RT-PCR analysis based on intron-spanning primers proves expression of hOR17-4 in human olfactory epithelium. PCR-products amplified from potential contaminating traces of genomic DNA can be distinguished by size. In sperm, the most potent hOR17-4 agonist is the odorant bourgeonal, whereas the receptor is antagonized by undecanal [3]. Therefore, we investigated olfactory perception of bourgeonal after brief undecanal exposure. 488 subjects (male and female, 21–37 years of age) were separated into one experimental group, sniffing bourgeonal–undecanal–bourgeonal (BUB) in succession, and various control groups (sniffing either bourgeonal three times (BBB) or a control odorant X–undecanal–odorant X (XUX) in succession). Odorants were presented for five seconds with brief interstimulus intervals (ISI) of 2 s and intensities as well as hedonics were obtained as previously described [5]. Intensity (Figure 1D) and quality (data not shown) ratings after undecanal exposure were then compared to the initial ratings (for the BBB control group responses to the first and the last stimulus were compared). Subjects of the BBB group reported consistent intensities for the three trials (105.1 ± 6.2 %), indicating no sign of adaptation. In contrast, the experimental group (BUB) showed a significant decrease in bourgeonal intensity after brief exposure to undecanal (35.8 ± 2.6%). Such an undecanal dependent effect was not reported by subjects rating the intensity of helional (91.3 ± 9.5%), an odorant structurally related to bourgeonal, geraniol (87.7 ± 7.2%), octanal (104.3 ± 13.9%), isoamyl acetate (99.4 ± 10.1%), vanillin (80.4 ± 24.9%), or eucalyptol (82.2 ± 10.1%). In all groups, no sex-related differences were observed and hedonic ratings changed only slightly after