Protein-bound Male Urinary Pheromones: Differential Responses According to Age and Gender (original) (raw)
Related papers
Pheromone binding by polymorphic mouse major urinary proteins
Protein Science, 2009
Mouse major urinary proteins (MUPs) have been proposed to play a role in regulating the release and capture of pheromones. Here, we report affinity measurements of five recombinant urinary MUP isoforms (MUPs-I, II, VII, VIII, and IX) and one recombinant nasal isoform (MUP-IV) for each of three pheromonal ligands, (±)-2-sec-butyl-4,5-dihydrothiazole (SBT), 6-hydroxy-6-methyl-3-heptanone (HMH), and (±)dehydro-exo-brevicomin (DHB). Dissociation constants for all MUP-pheromone pairs were determined by isothermal titration calorimetry, and data for SBT were corroborated by measurements of intrinsic protein fluorescence. We also report the isolation of MUP-IV protein from mouse nasal extracts, in which MUP-IV mRNA has been observed previously. The affinity of each MUP isoform for SBT (K d ∼ 0.04 to 0.9 M) is higher than that for DHB (K d ∼ 26 to 58 M), which in turn is higher than that for HMH (K d ∼ 50 to 200 M). Isoforms I, II, VIII, and IX show very similar affinities for each of the ligands. MUP-VII has approximately twofold higher affinity for SBT but approximately twofold lower affinity for the other pheromones, whereas MUP-IV has ∼23-fold higher affinity for SBT and approximately fourfold lower affinity for the other pheromones. The variations in ligand affinities of the MUP isoforms are consistent with structural differences in the binding cavities of the isoforms. The data indicate that the concentrations of available pheromones in urine may be influenced by changes in the expression levels of urinary MUPs or the excretion levels of other MUP ligands. The variation in pheromone affinities of the urinary MUP isoforms provides only limited support for the proposal that MUP heterogeneity plays a role in regulating profiles of available pheromones. However, the binding data support the proposed role of nasal MUPs in sequestering pheromones and possibly transporting them to their receptors.
Behaviour, 1999
The role of urinary chemosignals in sexual interactions was investigated in pairs of adult mice. Based on previous ndings, volatile molecules bound by the Major Urinary Proteins (MUPs) from adult male urine were thought to be suf cient to carry information about the sex of the emitter, and thus suf cient to modify the behaviour of conspeci cs. In the rst experiment, virgin and stud adult males were exposed to receptive females painted or not with MUPs-borne molecules. Both virgin and stud males showed an increased latency to the rst anogenital sniff and a reduced number of snif ngs towards MUPs-treated females. This suggests that adult mice are repelled by MUPs-borne volatile molecules, even in the presence of female stimuli conveyed by receptive mates. In the second experiment only stud males were tested, with ovariectomized or estrogenprimed females. These latter were either untreated, painted with MUPs-borne molecules or MUPs without volatile ligands. Ovariectomized females and those treated with MUPs without ligands received less sniffs than the other two groups. Estrogen-primed females were mounted more times, with a shorter latency. Ovariectomized females and females treated with MUPs-borne ligands were attacked earlier by males. The presence of chemical cues from male urine is thus suf cient to modify the behaviour of stud males towards receptive females. In particular, MUPs-borne volatiles are suf cient to act as male cues and to induce aggression towards receptive females. It can be speculated that in nature adult male mice rely on olfactory cues like MUPs-borne odorants to rstly identify a male conspeci c and possibly use similar chemical cues from their own urine to signal their presence.
Modulation of Exploratory Behavior in Female Mice by Protein-Borne Male Urinary Molecules
2002
Male pheromones are believed to attract females and repel male mice in open field tests but, when tested in more complex environments, they can attract male mice in usually avoided areas. Females were tested in an apparatus with one dark and one light side, in the absence or presence of male urine or the major urinary proteins (MUPs) bearing the natural ligands. Diestrous females were slower in leaving from the dark area when male urine or MUPs were present in it. Estrogen-primed females showed the opposite behavior, with an increase in the same latency. The light-avoidance behavior of prepubertal females, or females reared without males was not influenced by the presence of male chemosignals. The results show that adult female mice can react to MUPborne volatiles as to adult male urine and use them as cues of male mice, if they were previously exposed to male cues during infancy. MUP-borne molecules are, thus, the olfactory trace of males in the environment and modulate mice exploratory behavior.
Regulation of volatile and non-volatile pheromone attractants depends upon male social status
Scientific Reports, 2019
We investigated the regulation of chemical signals of house mice living in seminatural social conditions. We found that male mice more than doubled the excretion of major urinary proteins (MUPs) after they acquired a territory and become socially dominant. MUPs bind and stabilize the release of volatile pheromone ligands, and some MUPs exhibit pheromonal properties themselves. We conducted olfactory assays and found that female mice were more attracted to the scent of dominant than subordinate males when they were in estrus. Yet, when male status was controlled, females were not attracted to urine with high MUP concentration, despite being comparable to levels of dominant males. To determine which compounds influence female attraction, we conducted additional analyses and found that dominant males differentially upregulated the excretion of particular MUPs, including the pheromone MUP20 (darcin), and a volatile pheromone that influences female reproductive physiology and behavior. Our findings show that once male house mice become territorial and socially dominant, they upregulate the amount and types of excreted MUPs, which increases the intensities of volatiles and the attractiveness of their urinary scent to sexually receptive females. House mice (Mus musculus) excrete large quantities of major urinary proteins (MUPs) that bind and transport hydrophobic ligands, including several volatile pheromones 1-3. Upon excretion, MUPs slow down the release of volatiles from scent marks 4-8 , which may prolong their attraction and influence on conspecifics. MUPs are often suggested to show high individual diversity and thereby mediate individual and kin recognition 9,10. They are encoded by 21 paralogous loci, but MUP genes are highly homologous 11,12 and no individual variation has been detected in wild populations 13. Interestingly, MUP excretion is sexually dimorphic 5,14,15 , under endocrine control 16-18 , and dynamically regulated 19 depending upon health 20-22 , nutritional status 23 , and social interactions 24,25. Our aims here were to test whether house mice regulate the excretion of MUPs or volatile pheromone ligands depending upon their social status, and whether such regulation influences the attractiveness of their odor to potential mates 24. Male house mice are territorial and much evidence indicates that intra-and inter-sexual selection are mediated by chemosensory signals. Dominant territorial males scent mark their territories, and males deposit more scent-marks after winning an agonistic encounter compared to losers (winners are commonly labeled as 'dominants' and losers as 'subordinates') 26-28. Females are attracted to male urinary scent 29-31 and especially to the scent of 'dominant' males 32-35. Male reproductive success correlates with scent-marking when male social status is controlled and females are free to select their mates 36. Male urine also has priming effects on female reproductive physiology (accelerating puberty, synchronizing estrus, and blocking pregnancy 37), and especially if males are socially 'dominant' 38. Several volatile odor compounds (VOCs) have been identified as sexual pheromones (eliciting sexual attraction, priming effects, or both), including αand βfarnesene 39 , 2-sec-Butyl-4, 5-dihydrothiazole (SBT), 3, 4-dehydro-exo-brevicomin (DHB), and 6-hydroxy-6-methyl-3-heptanone (HMH 40), though not in all strains 41. Exposure to a combination of male pheromones (SBT, DHB, and HMH) induces female olfactory
Animal Reproduction Science, 2005
A previous investigation revealed that urine from normal male mice contained five unique volatile constituents; namely: 3-cyclohexene-1-methanol (I); 3-amino triazole (II); 4-ethyl phenol (III); 3ethyl-2,7-dimethyl octane (IV); 1-iodoundecane (V). The present study was designed to find out whether the production of these male specific urinary compounds was androgen-dependent. Urine of castrated and castrated plus testosterone-treated male mice was analyzed using gas chromatography linked mass spectrometry (GC-MS). Even though castrated male urine contained 10 detectable compounds, the five male specific compounds present in intact males were absent in castrated male mice urine. Only 3-ethyl-2,7-dimethyl octane (IV) reappeared following testosterone treatment into castrated males. Our earlier bioassay revealed that this compound was involved in attracting females. The present study concluded that this compound was a male specific volatile cue that acted as a releaser pheromone and its production was under the control of androgen.
Structural basis of pheromone binding to mouse major urinary protein (MUP-I)
Protein Science, 2001
The mouse major urinary proteins are pheromone-binding proteins that function as carriers of volatile effectors of mouse physiology and behavior. Crystal structures of recombinant mouse major urinary protein-I (MUP-I) complexed with the synthetic pheromones, 2-sec-butyl-4,5-dihydrothiazole and 6-hydroxy-6-methyl-3-heptanone, have been determined at high resolution. The purification of MUP-I from mouse liver and a high-resolution structure of the natural isolate are also reported. These results show the binding of 6-hydroxy-6-methyl-3-heptanone to MUP-I, unambiguously define ligand orientations for two pheromones within the MUP-I binding site, and suggest how different chemical classes of pheromones can be accommodated within the MUP-I -barrel.
Pheromones in Human Urine: A Study
Advances in Sexual Medicine, 2013
The present study was conducted to understand if pheromone or any similar substance was present in human semen and whether it could be recognized by smell. One hundred and fifty two subjects of either sex participated in this study. The study lasted for one month. They were to identify urine by smell. Daily first urine sample was submitted by five male and five female subjects for this study. Menstrual status of female subjects was recorded. Many distinguished the smell of urine of male from that of female. Interestingly male subjects recognized the smell of female urine of ovulation day. Reason may be pheromone. A woman may be releasing maximally pheromone on this day. This supports the theory of pheromone which attracts a man to a woman on her ovulation day.
Sex- and Gonad-Affecting Scent Compounds and 3 Male Pheromones in the Rat
Chemical Senses, 2008
This study was aimed at identifying sex pheromones of the rat (Rattus norvegicus). We characterized the volatiles and semivolatiles of rat preputial gland and voided urine by using gas chromatography-mass spectrometry (GC-MS) and quantified them by their GC areas (abundances) and percentage of GC areas (relative abundances). Although all the compounds other than 4-heptanone and phenol detected were shared by males and females, the quantities for some of these sex-common compounds exhibited sexual dimorphism and decreased with gonadectomy. Thus, these compounds might be sex pheromones. Among them, squalene from preputial glands and 2-heptanone and 4-ethyl phenol from urine were 3 major compounds. They were richer in males and could be suppressed by castration. Adding any of the 3 compounds (at a concentration higher than its physiological level in male urine) to castrated male urine (CMU) increased the attractiveness of CMU to sex-naive females. Adding the 3 together (at the levels in normal male urine) to CMU significantly increased the attractiveness of CMU to females. However, such combination did not fully restore females' preference for urine from intact males, suggesting that some other trace compounds such as 4-heptanone and phenol might also play some roles in sex attractiveness. Thus, squalene, 2-heptanone, and 4-ethyl phenol were indeed male pheromone molecules in rats. Our study also indicates that E,E-b-farnesene and E-a-farnesene, both richer in females than males, might be putative female pheromones.
An ephemeral sex pheromone in the urine of female house mice (Mus domesticus)
Behavioral and neural biology, 1992
From previous research, the ultrasonic vocalizations of male mice (Mus domesticus) to female mouse urine were hypothesized to be learned as a result of classical conditioning during adult heterosexual encounters. According to this interpretation, a previously neutral conditioned stimulus in female urine comes to elicit vocalizations as a result of its association with some other unknown unconditioned stimulus associated with adult females. However, the research from which this hypothesis was derived utilized urine collected from females housed in metabolic cages. Three experiments further examined the classical conditioning hypothesis using two types of female urine: (i) metabolic-cage-collected urine and (ii) freshly voided urine. Experiment 1 demonstrated that, in contrast to vocalizations to metabolic-cage-collected urine, adult heterosexual experience was not necessary for males to vocalize to freshly voided female urine. In addition, unlike metabolic-cage-collected urine (Exper...