Individual differences in sensitivity to the odor of 4,16-androstadien-3-one

Individual differences in sensitivity to the putative human pheromone androstadienone were investigated in three experiments. In experiment 1, the absolute detection threshold for androstadienone was determined to be 211 micro M using the method of constant stimuli. Detection for the related compound estratetraenol was also investigated but a threshold could not be determined. In experiment 2, using an adaptive threshold test on 100 participants, the sensitivity distribution for androstadienone, but not for the reference odor phenylethyl alcohol, was bimodal, with a smaller group of individuals with a high sensitivity to androstadienone (supersmellers). A lack of correlation between thresholds for androstadienone and phenylethyl alcohol further suggested that the bimodality for androstadienone was not due to individuals with a high general olfactory sensitivity. In line with an earlier observation, there was a statistical tendency for women to be more sensitive to androstadienone than men. Results of experiment 3 preclude the possibility that the bimodal sensitivity distribution for androstadienone would depend on individual differences in trigeminal activation. Altogether, the current study suggests that olfactory sensitivity to androstadienone is bimodally distributed in the population with a subgroup consisting of highly sensitive people.     

On the trigeminal percept of androstenone and its implications on the rate of specific anosmia

Specific anosmia is a term that describes an inability to perceive a particular odorant in the context of an otherwise normal olfactory acuity. The most common example, for the odor of androstenone, has been ascribed a prevalence ranging from 2 to 45%. In two experiments we sought to determine whether this wide range could be explained by the difference in steroid concentrations used, and by the degree to which the trigeminal system contributes to perception of androstenone. Experiment 1 demonstrated that high concentrations of androstenone stimulated the trigeminal system, as indicated by electrophysiological recordings. Experiment 2 demonstrated that conscious detection of androstenone is possible based solely on the trigeminal system. Interestingly, detection seems to interact with olfactory acuity in that subjects with a low olfactory sensitivity to androstenone were better able to detect its trigeminal component. The agreement between conscious experience and behavioral discrimination was not well calibrated, in that subjects demonstrated a clear overconfidence in their abilities. Altogether, the current study suggests that androstenone is an odorant that produces a concentration-dependent degree of trigeminal stimulation. This trigeminal component explains the diversity of the reported prevalence of specific anosmia for androstenone and might have implications on future use of specific anosmia as a tool to understand odor processing.     

Olfactory sensitivity of subjects working in odorous environments

The aim of the present study was to investigate whether people with a professional interest in odors also exhibit higher olfactory sensitivity. To this end, we investigated 58 subjects (age 33.6 +/- 11.0 years, mean +/- SD; 55 women) employed in perfume retail outlets and compared their olfactory sensitivity to 58 controls (age 34.6 +/- 9.9 years; 53 women) matched for age, gender and professional activities who did not work in such odorous environments. Olfactory function was assessed using the 'Sniffin' Sticks' test kit which includes tests for n-butanol odor threshold, odor discrimination and odor identification. Subjects working in perfume retail outlets scored higher in odor discrimination tests compared to controls. Working in an odorous environment for a full day had no major effect on general olfactory abilities, as indicated by measures performed at the beginning and end of a working day. Taken together, results from the present study do not support the idea that odorous environments are deleterious to general olfactory function.     

Enhanced urinary odor discrimination in female aromatase knockout (ArKO) mice

We asked whether odor discrimination abilities are sexually dimorphic in mice and, if so, whether the perinatal actions of estradiol contribute to these sex differences. The ability to discriminate different types of urinary odors was compared in male and female wild-type (WT) subjects and in mice with a homozygous-null mutation of the estrogen synthetic enzyme, aromatase (aromatase knockout; ArKO). Olfactory discrimination was assessed in WT and ArKO male and female mice after they were gonadectomized in adulthood and subsequently treated with estradiol benzoate. A liquid olfactometer was used to assess food-motivated olfactory discrimination capacity. All animals eventually learned to distinguish between urinary odors collected from gonadally intact males and estrous females; however, WT males as well as ArKO mice of both sexes learned this discrimination significantly more rapidly than WT females. Similar group differences were obtained when mice discriminated between urinary odors collected from gonadally intact vs. castrated males or between two non-social odorants, amyl and butyl acetate. When subjects had to discriminate volatile urinary odors from ovariectomized female mice treated with estradiol sequenced with progesterone versus estradiol alone, ArKO females quickly acquired the task whereas WT males and females as well as ArKO males failed to do so. These results demonstrated a strong sex dimorphism in olfactory discrimination ability, with WT males performing better than females. Furthermore, female ArKO mice showed an enhanced ability to discriminate very similar urinary odorants, perhaps due to an increased sensitivity of the main olfactory nervous system to adult estradiol treatment as a result of perinatal estrogen deprivation.     

Individual variability of human olfactory sensitivity to volatile steroids: Environmental and genetic factors

The sensitivity to androstenone and possible factors, determining the sensitivity were investigated for the large sample of inhabitants of central Russia (n = 860). Specific anosmia was detected in 48.8% of subjects. Women were more sensitive to androstenone than men. The proportion of men, but not women perceiving the smell of androstenone as a strong one in the concentration used decreased with age. Smoking, blood group, or ethnicity had no significant effect on the expression of specific anosmia and the perception of androstenone odor intensity.     

Odor identification, consistency of label use, olfactory threshold and their relationships to odor memory over the human lifespan.

The purpose of this study was to investigate olfactory threshold, odor identification, consistency of label use and their relationships to odor memory in the context of semantic/episodic memory across the human lifespan. A total of 137 subjects aged 4-90 years were tested with several olfactory test procedures. We found that olfactory sensitivity was well developed in children despite the finding that their odor naming and odor memory were inferior to that of adults. In the elderly population, olfactory functions gradually declined, with odor memory and odor identification demonstrating the most significant decline. Semantic encoding was differentially related to odor memory over the human age span. Whereas consistency of label use was the main predictor for odor memory in children and young adults, olfactory identification ability was the main predictor in the elderly study group. We also calculated response bias for the separate age groups and found no differences between children, young adults and elderly. However, with age false alarm rates increased. We conclude that children possess equal olfactory sensitivity compared with adults; however, due to limitations in linguistic capabilities and familiarity to odorants, odor memory and odor identification performance was limited. Additionally, our data indicate major alterations of olfactory processing in advanced age with substantial losses in odor memory and odor identification performance.     

Sensory detection of glutaraldehyde in drinking water-emergence of sensitivity and specific anosmia

A study of 30 young adults (15 males, 15 females), screened to have normal olfaction, measured detection of the flavor of glutaraldehyde, a biocide that could occur in disinfected potable water. Over the range of interest, up to 100 p.p.m., flavor derived from olfactory stimulation. Higher concentrations would cause oral irritation. Fourteen subjects failed to detect the glutaraldehyde in the first of four sessions of testing. Eight of the 14 (seven males, one female) continued to exhibit the anosmia throughout testing. The other six (one male, five females) began to detect the material in session two and exhibited increasing sensitivity over sessions two to four. Their average sensitivity never reached that of the 16 subjects who evinced no anosmia and who also improved their performance over sessions. The combined group of 22 could detect 17 p.p.m. Less thorough testing would have yielded much higher values. Specific anosmia for this dialdehyde has precedence in anosmia for various monoaldehydes, most notably isobutyraldehyde. The positive influence of experience with a material on detection has been found previously, most intriguingly by Wysocki and colleagues, who showed that experience could differentially induce sensitivity to the odorant androstenone and suggested that the phenomenon might occur for other compounds. Glutaraldehyde appears to be one, perhaps of many.     

Peripubertal exposure to male odors influences female puberty and adult expression of male-directed odor preference in mice

Testosterone-dependent olfactory signals emitted by male are well known to accelerate female puberty in mice (Vandenbergh effect). However, it remains unclear whether these chemosignals also influence adult expression of male-directed odor preference. Therefore, we exposed female mice to intact or castrated male bedding (vs clean bedding as control) during the peripubertal period (postnatal day (PD) 21–38) and measured male-directed odor preference in adulthood. At PD45 or PD60, females exposed to intact male odors, and thus showing puberty acceleration, preferred to investigate odors from intact males over females or castrated males. Females exposed to castrated male odors did not show puberty acceleration but preferred male (intact or castrated) over female odors. Finally, control females did not show any odor preference when tested at PD45, although a preference for male odors emerged later (PD60). In a second experiment, females that were exposed to intact male odors after pubertal transition (PD36–53) also preferred intact male over castrated male odors. In conclusion, our results indicate that peripubertal exposure to male odors induced early expression of male-directed odor preference regardless of puberty-accelerating effect and that induction of male-directed odor preference is not specific to the peripubertal period.     

Peri-pubertal exposure to testicular hormones organizes response to novel environments and social behaviour in adult male rats

Previous research has shown that exposure to testicular hormones during the peri-pubertal period of life has long-term, organizational effects on adult sexual behaviour and underlying neural mechanisms in laboratory rodents. However, the organizational effects of peri-pubertal testicular hormones on other aspects of behaviour and brain function are less well understood. Here, we investigated the effects of manipulating peri-pubertal testicular hormone exposure on later behavioural responses to novel environments and on hormone receptors in various brain regions that are involved in response to novelty. Male rodents generally spend less time in the exposed areas of novel environments than females, and this sex difference emerges during the peri-pubertal period. Male Lister-hooded rats (Rattus norvegicus) were castrated either before puberty or after puberty, then tested in three novel environments (elevated plus-maze, light–dark box, open field) and in an object/social novelty task in adulthood. Androgen receptor (AR), oestrogen receptor (ER1) and corticotropin-releasing factor receptor (CRF-R2) mRNA expression were quantified in the hypothalamus, hippocampus and medial amygdala. The results showed that pre-pubertally castrated males spent more time in the exposed areas of the elevated-plus maze and light–dark box than post-pubertally castrated males, and also confirmed that peri-pubertal hormone exposure influences later response to an opposite-sex conspecific. Hormone receptor gene expression levels did not differ between pre-pubertally and post-pubertally castrated males in any of the brain regions examined. This study therefore demonstrates that testicular hormone exposure during the peri-pubertal period masculinizes later response to novel environments, although the neural mechanisms remain to be fully elucidated.     

5-α-androst-16en-3α-on: A male pheromone? A brief report

Olfactory cues play a prominent, yet underestimated role in shaping emotional attitudes towards conspecifics. Among humans olfactory cues can have effects on behavior. In a rating study (n = 290) females rated the smell of androstenone. The emotional reaction to androstenone changed during the menstrual cycle. Females rated the main component of male body odor unattractive. This changed to a neutral emotional response at the conceptive optimum around ovulation. The finding has direct consequences for hypotheses concerning the evolutionary loss of estrus. It is suggested that the cyclic-dependent emotional rating of androstenone may facilitate active female choice of sex partners and may be a proximate cue for female mate-choice.     

The production of and sensitivity to cues that delay puberty and prolong subsequent oestrous cycles in female mice are influenced by prior intrauterine position

Four experiments were conducted with CF-1 house mice (Mus domesticus) to examine the relationship between a female's prior intrauterine position (2M = between 2 male fetuses, 1M = next to one male fetus, 0M = not next to a male fetus) and the timing of puberty and length of subsequent oestrous cycles under a variety of housing conditions. The results of Exp. 1 confirmed that the presence of males was required for females to enter puberty and exhibit regular oestrous cycles, regardless of prior intrauterine position. When housed individually after weaning either with a male in the cage or separated by a wire mesh partition, 0M-females ovulated and mated at a younger age and had shorter post-pubertal oestrous cycles than did 2M-females (1M-females were intermediate between 0M- and 2M-females). Other females were also housed after weaning with a male or separated by a wire mesh partition from a male in a variety of social environments (4 0M-females and 1 2M-female, 4 2M-females and 1 0M-female, 5 1M-females, 3 0M-females and 3 2M-females). The objective of these different housing conditions was to determine whether prior intrauterine position influenced the transmission of and/or sensitivity to cues that delay puberty and prolong subsequent oestrous cycles. Relative to 2M-females, 0M-females both produced more potent cues and were more sensitive to the cues (again, 1M-females were intermediate between 0M- and 2M-females). Specifically, in the presence of other females, puberty was delayed and post-pubertal oestrous cycles were prolonged to the greatest extent in 0M-females. Prior intrauterine position is therefore a source of individual variation in the production of and sensitivity to cues that modulate the timing of puberty and the length of subsequent oestrous cycles in female mice. The findings suggest that prenatally-androgenized 2M-females may have a reproductive advantage over other females at high population densities.     

Olfaction and Environment: Tsimane’ of Bolivian Rainforest Have Lower Threshold of Odor Detection Than Industrialized German People

Olfactory sensitivity varies between individuals. However, data regarding cross-cultural and inter-group differences are scarce. We compared the thresholds of odor detection of the traditional society of Tsimane’ (native Amazonians of the Bolivian rainforest; n = 151) and people living in Dresden (Germany; n = 286) using “Sniffin’ Sticks” threshold subtest. Tsimane’ detected n-butanol at significantly lower concentrations than the German subjects. The distribution of thresholds of the Tsimane’ was very specific, with 25% of Tsimane’ obtaining better results in the olfactory test than any member of the German group. These data suggest that differences in olfactory sensitivity seem to be especially salient between industrialized and non-industrialized populations inhabiting different environmental conditions. We hypothesize that the possible sources of such differences are: (i) the impact of pollution which impairs the olfactory abilities of people from industrialized countries; (ii) better training of olfaction because of the higher importance of smell in traditional populations; (iii) environmental pressures shaping olfactory abilities in these populations.     

'Sniffin' Sticks': Olfactory Performance Assessed by the Combined Testing of Odour Identification, Odor Discrimination and Olfactory Threshold

‘Sniffin’ Sticks' is a new test of nasal chemosensoryperformance based on pen-like odor dispensing devices. It comprisesthree tests of olfactory function, namely tests for odor threshold(n-butanol, testing by means of a single staircase), odor discrimination(15 pairs of odorants, triple forced choice) and odor identification(16 common odorants, multiple forced choice from four verbalitems per test odorant). After extensive preliminary investigationsthe tests were applied to a group of 104 healthy volunteers(52 female, 52 male, mean age 49.5 years, range 18–84years) in order to establish test-retest reliability and tocompare them with an established measure of olfactory performance(the Connecticut Chemosensory Clinical Research Center Test,CCCRC). Performance decreased with increasing age of the subjects(     

Factors influencing aggression toward females by male rats exposed to anabolic androgenic steroids during puberty

Previous results showed that male rats pubertally exposed to anabolic androgenic steroids (AAS) displayed aggression towards females in response to physical provocation. This experiment examined two factors that may modulate AAS-induced behavior towards females: olfactory cues and frustration. Gonadally intact males began one of three AAS treatments at puberty (D40): testosterone propionate (T), stanozolol (S), T+S, or vehicle control. To test for the relevance of olfactory cues in the elicitation of behavior toward females, a hidden neighbor paradigm was used. The proximal stimulus was an ovariectomized (OVX) female, estrogen plus progesterone (E+P) female, or an E+P female with tape-obstructed vagina (OBS). Distal olfactory cues from a hidden neighbor were delivered from a separate cage connected to the testing arena. The vaginally obstructed, sexually receptive female (OBS) was used to determine the effects of frustration on behavior by AAS males. Both sexual and aggressive behaviors were measured. The presence of distal olfactory cues had no effect on either sexual or aggressive behavior. In the presence of E+P and OBS females, all males displayed sex behaviors, not aggression. However, AAS males displayed significantly more aggression towards proximal OVX females than controls. AAS males mounted OBS females significantly more than controls, indicating a persistence of once rewarded behavior. These results suggest (1) proximal cues of the conspecific female are more salient than distal olfactory cues in determining behavior and (2) AAS males display frustration-induced persistence in response to vaginally obstructed receptive females.     

Prepubertal castration eliminates sex differences in lifespan and growth trajectories in genetically heterogeneous mice

Sex differences in aging and longevity have been widely observed, with females consistently outliving males across human populations. However, the mechanisms driving these disparities remain poorly understood. In this study, we explored the influence of post-pubertal testicular effects on sex differences in aging by prepubertally castrating genetically heterogeneous (UM-HET3) mice, a unique mouse model that emulates human sex differences in age-related mortality. Prepubertal castration eliminated the longevity disparity between sexes by reducing the elevated early- to mid-life mortality rate observed in males and extending their median lifespan to match that of females. Additionally, castration extended the duration of body weight growth and attenuated the inverse correlation between early-age body weight and lifespan in males, aligning their growth trajectories with those of females. Our findings suggest that post-pubertal testicular actions in genetically diverse mice are primarily responsible for sex differences in longevity as well as growth trajectories. These findings offer a foundation for further investigation into the fundamental mechanisms driving sex-specific aging patterns and the development of potential pro-longevity interventions.     

High hunger state increases olfactory sensitivity to neutral but not food odors

Understanding how hunger state relates to olfactory sensitivity has become more urgent due to their possible role in obesity. In 2 studies (within-subjects: n = 24, between-subjects: n = 40), participants were provided with lunch before (satiated state) or after (nonsatiated state) testing and completed a standardized olfactory threshold test to a neutral odor (Experiments 1 and 2) and discrimination test to a food odor (Experiment 2). Experiment 1 revealed that olfactory sensitivity was greater in the nonsatiated versus satiated state, with additionally increased sensitivity for the low body mass index (BMI) compared with high BMI group. Experiment 2 replicated this effect for neutral odors, but in the case of food odors, those in a satiated state had greater acuity. Additionally, whereas the high BMI group had higher acuity to food odors in the satiated versus nonsatiated state, no such differences were found for the low BMI group. The research here is the first to demonstrate how olfactory acuity changes as a function of hunger state and relatedness of odor to food and that BMI can predict differences in olfactory sensitivity.     

Influence of growth and athletic training on heart and lung functions.

Studies were performed at rest and during exercise of varied intensity on 52 boys of pre- and post-pubescent age. Each age group consisted of boys who were engaged in a strenuous prolonged hockey training program; this group was compared with a matched control group who did not participate in a regular training program. Any differences observed in the measured lung functions could be explained on the basis of physical size. Relationship of pulmonary capillary blood flow (Qc) and pulmonary diffusing capacity (DLco) to oxygen consumption were similar to those reported for adults and no difference between the trained and control groups was found in either the pre- or post-pubertal aged boys. Similarily, the trained pre-pubertal boys did not differ significantly from their matched control group in respect to the relationships of heart rate (HR) and stroke volume (SV) for any level of oxygen consumption. In contrast, the post-pubertal trained boys had significantly lower HR and higher SV (P less than 0.01) at each level of work than the control group. These differences between the trained and control post-pubertal boys are consistent with training effects observed in adults. The lack of differences between the trained and control pre-pubertal groups was surprising. Whether the differences in the post-pubertal groups due to a detraining effect in the post-pubertal control boys (as compared to the pre-pubertal control group) or to a continued high level of physical activity during and after the on-set of puberty in trained boys cannot be answered by this study. The findings suggest the importance of high intensity exercise programs during the growth period of adolescence if the efficiency of the oxygen delivery system, and possibly its ultimate dimensions, are to be enhanced.     

Olfactory responsiveness to two odorous steroids in three species of nonhuman primates

Social communication by means of odor signals is widespread among mammals. In pigs, for example, the C19-steroids 5-alpha-androst-16-en-3-one and 5-alpha-androst-16-en-3-ol are secreted by the boar and induce the mating stance in the sow. In humans, the same substances have been shown to be compounds of body odor and are presumed to affect human behavior. Using an instrumental conditioning paradigm, we here show that squirrel monkeys, spider monkeys and pigtail macaques are able to detect androstenone at concentrations in the micromolar range and thus at concentrations at least as low as those reported in pigs and humans. All three species of nonhuman primates were considerably less sensitive to androstenol, which was detected at concentrations in the millimolar range. Additional tests, using a habituation-dishabituation paradigm, showed that none of the 10 animals tested per species was anosmic to the two odorous steroids. These results suggest that androstenone and androstenol may be involved in olfactory communication in the primate species tested and that the specific anosmia to these odorants found in approximately 30% of human subjects may be due to their reduced number of functional olfactory receptor genes compared with nonhuman primates.     

Different odor tests contribute differently to the evaluation of olfactory loss

In a clinical context, the importance of the sense of smell has increasingly been recognized, for example, in terms of the evaluation of neurodegenerative disorders. In this study, 2 strategies of olfactory testing, a simple one and a more complex one, were compared with respect to their suitability to assess olfactory dysfunction. Odor threshold (T), discrimination (D), and identification (I) were assessed in a control sample of 916 males and 1160 females, aged 6-90 years, and in 81 men and 21 women, aged 38-80 years, suffering from idiopathic Parkinson's disease (IPD). Sums of the 3 subtest results T, D, and I yielded threshold discrimination identification (TDI) scores reflecting olfactory function. Sensitivity of any of the 3 subtests to confirm the diagnosis established by the composite TDI score was assessed separately for each test. Principal component analyses were applied to determine any common source of variance among the 3 specific subtests. Sensitivities of the subtests to provide the diagnosis established by the composite TDI score were 64% (T), 56% (D), and 47% (I), respectively. In IPD patients, each of the subtests provided the correct diagnosis (sensitivity >90%), as olfaction was impaired in 99% of the patient group. Two principal components emerged in both controls and IPD patients, with eigenvalues >0.5. The first component received high loadings from all factors. The second component received high loadings from odor threshold, whereas loadings from odor discrimination and identification were much smaller. In conclusion, combined testing of several components of olfaction, especially including assessment of thresholds, provides the most significant approach to the diagnosis of smell loss.