Ana G. Gutiérrez-García, Carlos M. Contreras & Remedios Mendoza-López
Universidad Veracruzana, México
Abstract:
2-Heptanone is an alarm pheromone contained in some human fluids, but its role is unknown in chemical communication. In part one of this study, a sample of 24 women provided urine specimens taken around their supposed ovulation days, and a second sample 12 days later. As exclusion criteria, women with anxiety (based on the State-Trait Anxiety Inventory, Spielberger), mood disorders (based on the Clinical Diagnosis of Depression Questionnaire), and premenstrual dysphoric disorder (based on the Daily Symptoms Report) were not included in the study. Gas chromatography/mass spectrometry indicated that urinary 2-heptanone content was increased approximately two-fold during pre-menstruation compared with the days around ovulation. In part two of this study, 141 male and female volunteers, sniffed this ketone and with a simple questionnaire it was determined that the longest tested duration (180 s) of sniffing 2-heptanone lowered the acceptance of sniffing this ketone again, compared with the shorter sniffing durations (5 and 60 s), with no differences between sexes. The increased concentration of 2-heptanone during the day before menstruation may be considered as part of the functional changes preceding menstruation and sniffing this ketone may produce sensorial-emotional changes depending on time of sniffing, the significance of this deserves further study.
Keywords: 2-Heptanone, Chemosignals, Menstrual cycle, Pheromones, Olfactory system
References:
Achiraman, S., Archunan, G., Sankarganesh, D., Rajagopal, T., Rengarajan, R. L., Kokilavani, P., …, & Kannan, S. (Aug, 2011). Biochemical analysis of female mice urine with reference to endocrine function: a key tool for estrus detection. Zoological Science, 28(8), 600-605. http://dx.doi.org/10.2108/zsj.28.600
Ackerl, K., Atzmueller, M., & Grammer, K. (Apr, 2002). The scent of fear. Neuroendocrinology Letters, 23(2), 79-84. Retrieved from http://bit.ly/1dCACMi
Ahn, R. S., Choi, J. H., Choi, B. C., Kim, J. H., Lee, S. H., & Sung, S. S. (Dec, 2011). Cortisol, estradiol-17β, and progesterone secretion within the first hour after awakening in women with regular menstrual cycles. Journal of Endocrinology, 211(3), 285-295. doi: 10.1530/JOE-11-0247 Retrieved from http://bit.ly/1JZVclR
Albrecht, J., Demmel, M., Schöpf, V., Kleemann, A. M., Kopietz, R., May, J., …, & Wiesmann, M. (Jan, 2010). Smelling chemosensory signals of males in anxious versus nonaxious condition increases state anxiety of female subjects. Chemical Senses, 36(1), 19-27. doi: 10.1093/chemse/bjq087 Retrieved from http://bit.ly/1ADrsJt
Andreano, J. M., Arjomandi, H., & Cahill, L. (Jul, 2008). Menstrual cycle modulation of the relationship between cortisol and long-term memory. Psychoneuroendocrinology, 33(6), 874-882. doi: 10.1016/j. psyneuen.2008.03.009 Retrieved from http://bit.ly/1LOX9R7
Atasoy, A. F., Hayaloglu, A. A., Kirmaci, H., Levent, O. & Türkoǧlu, H. (Oct, 2013). Effects of partial substitution of caprine for ovine milk on the volatile compounds of fresh and mature Urfa cheeses. Small Ruminant Research, 115(1-3), 113-123. http://dx.doi.org/10.1016/j.smallrumres.2013.09.002
Cakmakci, S., Dagdemir, E., Hayaloglu, A. A., Gurses, M., Cetin, B. & Tahmas-Kahyaoglu, D. (Aug, 2013). Effect of Penicillium roqueforti and incorporation of whey cheese on volatile profiles and sensory characteristics of mould-ripened Civil cheese. International Journal of Dairy Technology, 66(4), 512-526. doi: 10.1111/1471- 0307.12069 Retrieved from http://bit.ly/1Fflxpw
Calderón Narvaez, G. (1992). Cuestionario clínico para el diagnóstico de los cuadros depresivos. Revista Médica IMSS, 30, 377-380.
Carnielli, V. P., Sulkers, E. J., Moretti, C., Wattimena, J. L., Goudoever van, J. B., Degenhart, H. J., …, & Sauer, P. J. (Oct, 1994). Conversion of octanoic acid into long-chain saturated fatty acids in premature infants fed a formula containing medium-chain triglycerides. Metabolism: Clinical and Experimental, 43(10), 1287- 1292. Retrieved from http://bit.ly/1RwyrIj
Chen, D., & Haviland-Jones, J. (Dec, 2000). Human olfactory communication of emotion. Perceptual and Motor Skills, 91(3 Pt 1), 771-781. doi: 10.2466/pms.2000.91.3.771
Childs, E., Dlugos, A., & De Wit, H. (May, 2010). Cardiovascular, hormonal, and emotional responses to the TSST in relation to sex and menstrual cycle phase. Psychophysiology, 47(3), 550-559. doi: 10.1111/j.1469- 8986.2009.00961.x Retrieved from http://bit.ly/1coDmeL
Contreras, C. M., Gutiérrez-García, A. G. & Molina-Jiménez, T. (Sep, 2013). Anterior olfactory organ removal produces anxiety-like behavior and increases spontaneous neuronal firing rate in basal amygdala. Behavioural Brain Research, 252, 101-109. doi:10.1016/j.bbr.2013.05.037 Retrieved from http://bit.ly/1BvifOj
Contreras, C. M., Gutiérrez-García, A. G., Molina-Jiménez, T., & Mendoza-López, M. R. (Aug, 2012). 2-Heptanone increases the firing rate of the basal amygdala: role of anterior olfactory epithelial organs. Neuropsychobiology, 66(3), 167-173. doi: 10.1159/000339946 Retrieved from http://bit.ly/1Rwymo3
Delgado, F. J., González-Crespo, J., Cava, R., & Ramírez, R. (Dec, 2011). Formation of the aroma of a raw goat milk cheese during maturation analysed by SPME-GC-MS. Food Chemistry, 129(3), 1156-1163. doi:10.1016/j. foodchem.2011.05.096 Retrieved from http://bit.ly/1HYb1as
Derntl, B., Kryspin-Exner, I., Fernbach, E., Moser, E., & Habel, U. (Jan, 2008a). Emotion recognition accuracy in healthy young females is associated with cycle phase. Hormones and Behavior, 53(1), 90-95. doi:10.1016/j. yhbeh.2007.09.006 Retrieved from http://bit.ly/1SHEifC
Derntl, B., Windischberger, C., Robinson, S., Lamplmayr, E., Kryspin-Exner, I., Gur, R.C., …, & Habel, U. (Sep, 2008b). Facial emotion recognition and amygdala activation are associated with menstrual cycle phase. Psychoneuroendocrinology, 33(8), 1031-1040. doi:10.1016/j.psyneuen.2008.04.014 Retrieved from http://bit.ly/1GKzfX1
Distel, H., Ayabe-Kanamura, S., Martínez-Gómez, M., Schicker, I., Kobayakawa, T., Saito, S., & Hudson, R. (Apr, 1999). Perception of everyday odors: correlation between intensity, familiarity and strength of hedonic judgement. Chemical Senses, 24(2), 191-199. doi: 10.1093/chemse/24.2.191. Retrieved from http://bit.ly/1Ku5rwL
Djurhuus, C. B., Gravholt, C. H., Nielsen, S., Mengel, A., Christiansen, J. S., Schmitz, O. E., & Møller, N. (Jul, 2002). Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans. American Journal of Physiology and Endocrinology Metabolism, 283(1), E172-E177. Doi: 10.1152/ajpendo.00544.2001. Retrieved from http://bit.ly/1dCAsEw
Duchesne, A., & Pruessner, J. C. (Dec, 2013). Association between subjective and cortisol stress response depends on the menstrual cycle phase. Psychoneuroendocrinology, 38(12), 3155-3159. doi: 10.1016/j. psyneuen.2013.08.009 Retrieved from http://bit.ly/1Ku5t7L
Freeman, E. W., DeRubeis, R. J., & Rickels, K. (Nov, 1996). Reliability and validity of a daily diary for premenstrual syndrome. Psychiatry Research, 65(2), 97-106. doi:10.1016/S0165-1781(96)02929-0. Retrieved from http://bit.ly/1ADrfFS
Gallagher, M., Wysocki, C. J., Leyden, J. J., Spielman, A. I., Sun, X., & Preti, G. (Sep, 2008). Analyses of volatile organic compounds from human skin. British Journal of Dermatology, 159(4), 780-791. doi: 10.1111/j.1365- 2133.2008.08748.x Retrieved from http://1.usa.gov/1eEzYOv
Gehrig, R. F., & Knight, S. G. (Nov, 1958). Formation of ketones from fatty acids by spores of Penicillium roqueforti. Nature, 182(4644), 1237. doi:10.1038/1821237a0
Gildersleeve, K. A., Haselton, M. G., Larson, C. M., & Pillsworth, E. G. (Feb, 2012). Body odor attractiveness as a cue of impending ovulation in women: evidence from a study using hormone-confirmed ovulation. Hormones and Behavior, 61(2), 157-166. doi: 10.1016/j.yhbeh.2011.11.005. Retrieved from http://bit.ly/1J9y7xL
Gröschl, M., Rauh, M., Schmid, P. & Dörr HG. (Sep, 2001). Relationship between salivary progesterone, 17-hydroxyprogesterone, and cortisol levels throughout the normal menstrual cycle of healthy postmenarcheal girls. Fertility and Sterility, 76(3), 615-617. Retrieved from http://bit.ly/1d4P0Mv
Guapo, V. G., Graeff, F. G., Zani, A. T., Labate, C.M., dos Reis, R. M., & Del-Ben, C.M. (Aug, 2009). Effects of sex hormonal levels and phases of the menstrual cycle in the processing of emotional faces. Psychoneuroendocrinology, 34(7), 1087-1094. doi: 10.1016/j.psyneuen.2009.02.007. Retrieved from http://bit.ly/1FkKG3c
Gutiérrez-Castellanos, N., Martínez-Marcos, A., Martínez-García, F., & Lanuza, E. (Sep, 2010). Chemosensory function of the amygdala. Vitamins and Hormones, 83, 165-196. doi: 10.1016/S0083-6729(10)83007-9
Gutiérrez-García, A. G., & Contreras, C. M. (Mar, 2013). Anxiety: an adaptive emotion. In F. Durbano (Ed.), New Insights into Anxiety Disorders (pp. 21-37). Rijeka, Croacia: INTECH. doi: 10.5772/53223 Retrieved from http://bit.ly/1LOX0xb
Gutiérrez-García, A. G., Contreras, C. M., Mendoza-López, M. R., Cruz-Sánchez, S., García-Barradas, O., Rodríguez-Landa, J. F., & Bernal-Morales, B. (Feb, 2006). A single session of emotional stress produces anxiety in Wistar rats. Behavioural Brain Research, 167(1), 30-35. doi:10.1016/j.bbr.2005.08.011 Retrieved from http://bit.ly/1FJmwBT
Gutiérrez-García, A. G., Contreras, C. M., Mendoza-López, M. R., García-Barradas, O., & Cruz-Sánchez, J. S. (Feb, 2007). Urine from stressed rats increases immobility in receptor rats forced to swim: role of 2-heptanone. Physiology and Behavior, 91(1), 166-172. doi:10.1016/j.physbeh.2007.02.006 Retrieved from http://bit.ly/1Bvi6un
Hlavacova, N., Wawruch, M., Tisonova, J., & Jezova, D. (Dec, 2008). Neuroendocrine activation during combined mental and physical stress in women depends on trait anxiety and the phase of the menstrual cycle. Annals of the New York Academy of Sciences, 1148, 520-525. doi: 10.1196/annals.1410.030 Retrieved from http://bit.ly/1FkKEIG
Jong-Yeon, K., Hickner, R. C., Dohm, G. L., & Houmard, J. A. (Apr, 2002). Long- and medium-chain fatty acid oxidation is increased in exercise-trained human skeletal muscle. Metabolism, 51(4), 460-464. doi:10.1053/ meta.2002.31326 Retrieved from http://bit.ly/1FSDCyx
Jurado, S., Villegas, M., Méndez, L., Rodríguez, F., Loperena, V., & Varela. R. (1998, mayo-jun). La estandarización del inventario de depresión de Beck para los residentes de la Ciudad de México. Salud Mental, 21(3), 26-31. Recuperado de http://bit.ly/1HTjvlU
Kiyokawa, Y., Kikusui, T., Takeuchi, Y., & Mori, Y. (May, 2005). Mapping the neural circuit activated by alarm pheromone perception by c-fos inmunihistochemistry. Brain Research, 1043(1-2), 145-154. doi:10.1016/j. brainres.2005.02.061 Retrieved from http://bit.ly/1FSDwa1
Kudielka, B. M., & Kirschbaum, C. (Jan, 2003). Awakening cortisol responses are influenced by health status and awakening time but not by menstrual cycle phase. Psychoneuroendocrinology, 28(1), 35-47. doi:10.1016/ S0306-4530(02)00008-2 Retrieved from http://bit.ly/1PTBYTU
Lacy Costello de, B., Amann, A., Al-Kateb, H., Flynn, C., Filipiak, W., Khalid, T., …, & Ratcliffe, N. M. (Mar, 2014). A review of the volatiles from the healthy human body. Journal of Breath Research, 8(1), 014001. doi:10.1088/1752-7155/8/1/014001 Retrieved from http://bit.ly/1FJms54
Larroche, C. (Jan, 1996). Internal substrate concentrations during biotransformation of octanoic acid into 2-heptanone by spores of Penicillium roquefortii. Journal of Industrial Microbiology and Biotechnology, 16(1), 29-35. doi: 10.1007/BF01569918 Retrieved from http://bit.ly/1BvhVPL
Larroche, C., Besson, I., & Gros, J. B. (Feb, 1994). Behavior of spores of Penicillium roquefortii during fed-batch bioconversion of octanoic acid into 2-heptanone. Biotechnology and Bioengineering, 44(6), 699-709. doi: 10.1002/bit.260440606 Retrieved from http://bit.ly/1SHE4VE
Leinders-Zufall, T., Lane, A. P., Puce, A. C., Ma, W., Novotny, M., Shipley, M. T., & Zufall, F. (Nov, 2000). Ultrasensitive pheromone detection by mammalian vomeronasal neurons. Nature, 405(6788), 792-796. doi:10.1038/35015572.
Miller, S. L., & Maner, J. K. (Feb, 2010). Scent of a woman: men’s testosterone responses to olfactory ovulation cues. Psychological Sciences, 21(2), 276-283. doi: 10.1177/0956797609357733 Retrieved from http://bit.ly/1d4OPkd
Molina-Jiménez, T., Gutiérrez-García, A. G., & Contreras, C. M. (2013, jul-ago). An alarm pheromone increases the responsivity of amygdaline-hippocampal neurons. Salud Mental, 36(4), 279-284. Retrieved from http://bit.ly/1Jdlf8g
Mujica-Parodi, L. R., Strey, H. H., Frederick, B., Savoy, R., Cox, D., Botanov, Y., …, & Weber, J. (Jul, 2009). Chemosensory cues to conspecific emotional stress activate amygdala in humans. PLoS One, 4(7), e6415. doi: 10.1371/journal.pone.0006415 Retrieved from http://bit.ly/1DfSm8t
Navarrete-Palacios, E., Hudson, R., Reyes-Guerrero, G., & Guevara-Guzmán, R. (Jul, 2003). Lower olfactory threshold during the ovulatory phase of the menstrual cycle. Biological Psychology, 63(3), 269-279. doi:10.1016/S0301-0511(03)00076-0 Retrieved from http://bit.ly/1PTBBZx
Navarrete-Palacios, Hudson, Reyes-Guerrero & Guevara-Guzmán (Jul, 2003). Lower olfactory threshold during the ovulatory phase of the menstrual cycle. Biol Psychol, 63(3), 269-279.
Novotny, M. V. (Feb, 2003). Pheromones, binding proteins and receptor responses in rodents. Biochemical Society Transactions, 31(Pt 1), 117-122. Retrieved from http://bit.ly/1RwxzDM
Osada, K., Yamazaki, K., Curran, M., Bard, J., Smith, B. C. P., & Beauchamp, G. K. (May, 2003). The scent of age. Proceeding Biological Sciences, 270(1518), 929-933. doi: 10.1098/rspb.2002.2308 Retrieved from http://bit.ly/1LSHI9S
Papamandjaris, A. A., MacDougall, D. E., & Jones, P. J. (Feb, 1998). Medium chain fatty acid metabolism and energy expenditure: obesity treatment implications. Life Sciences, 62(14), 1203-1215. doi:10.1016/S0024- 3205(97)01143-0 Retrieved from http://bit.ly/1HTj8b2
Pasanen, P., Korpi, A., Kalliokoski, P., & Pasanen, A. L. (Jun, 1997). Growth and volatile metabolite production of Aspergillus versicolor in house dust. Environment International, 23(4), 425-432. doi:10.1016/S0160- 4120(97)00027-5 Retrieved from http://bit.ly/1GKya1l
Pause, B. M., Ohrt, A., Prehn, A., & Ferstl, R. (Nov, 2004). Positive emotional priming of facial affect perception in females is diminished by chemosensory anxiety signals. Chemical Senses, 29(9), 797-805. doi: 10.1093/ chemse/bjh245 Retrieved from http://bit.ly/1GKy8Xm
Pause, B. M., Adolph, D., Prehn-Kristensen, A., & Ferstl, R. (Nov, 2009). Startle response potentiation to chemosensory anxiety signals in socially anxious individuals. International Journal of Psychophysiology, 74(2), 88-92. doi: 10.1016/j.ijpsycho.2009.07.008 Retrieved from http://bit.ly/1FJmdqt
Paz, R., & Pare, D. (Jun, 2013). Physiological basis for emotional modulation of memory circuits by the amygdala. Current Opinion Neurobiology, 23(3), 381-386. doi: 10.1016/j.conb.2013.01.008 Retrieved from http://1.usa.gov/1GKy8qa
Phelps, E. A. (Apr, 2002). Human emotional and memory: interaction of the amygdala and hippocampal complex. Current Opinion Neurobiology, 14, 198-202. doi:10.1016/j.conb.2004.03.015 Retrieved from http://bit.ly/1d4OH46
Pohorecky, L. A., Blakley, G. G., Ma, E. W., Soini, H. A., Wiesler, D., Bruce, K. E., & Novotny, M. V. (Apr, 2008). Social housing influences the composition of volatile compounds in the preputial glands of male rats. Hormones and Behavior, 53(4), 536-545. doi: 10.1016/j.yhbeh.2007.12.006 Retrieved from http://bit.ly/1FJm1aM
Prehn, A., Ohrt, A., Sojka, B., Ferstl, R. & Pause, B. M. (Feb, 2006). Chemosensory anxiety signals augment the startle reflex in humans. Neurosciences Letters, 394(2), 127-130. doi:10.1016/j.neulet.2005.10.012 Retrieved from http://bit.ly/1d4OGwZ
Prehn-Kristensen, A., Wiesner, C., Bergmann, T. O., Wolff, S., Jansen, O., Mehdorn, H. M., …, & Pause, B. M. (Jun, 2009). Induction of empathy by the smell of anxiety. PLoS One, 4(6), e5987. doi: 10.1371/journal. pone.0005987 Retrieved from http://bit.ly/1SHDRll
Puts, D. A., Bailey, D. H., Cárdenas, R. A., Burriss, R. P., Welling, L. L., Wheatley, J. R., & Dawood, K. (Jan, 2013). Women’s attractiveness changes with estradiol and progesterone across the ovulatory cycle. Hormones and Behavior, 63(1), 13-19. doi: 10.1016/j.yhbeh.2012.11.007 Retrieved from http://bit.ly/1d4OFJF
Reed, S. C., Levin, F. R., & Evans, S. M. (Jun, 2008). Changes in mood, cognitive performance and appetite in the late luteal and follicular phases of the menstrual cycle in women with and without PMDD (premenstrual dysphoric disorder). Hormones and Behavior, 54(1), 185-193. doi: 10.1016/j.yhbeh.2008.02.018 Retrieved from http://1.usa.gov/1coCOWb
Santos, J. E. R., Villarino, B. J., Zosa, A. R., & Dayrit, F. M. (Dec, 2011). Analysis of volatile organic compounds in virgin coconut oil and their sensory attibutes. Philippine Journal of Science, 140(2), 161-171. Retrieved from http://bit.ly/1FkKiSm
Schaft van der, P. H., Burg ter, N., Bosch van den, S., & Cohen, A. M. (Mar, 1992). Fed-batch production of 2-heptanone by Fusarium poae. Applied Microbiology and Biotechnology, 36(6), 709-711. doi: 10.1007/ BF00172179 Retrieved from http://bit.ly/1LSJQhO
Singh, D., & Bronstad, P. M. (Apr, 2001). Female body odor is a potential cue to ovulation. Proceeding Biological Sciences, 268(1469), 797-801. doi: 10.1098/rspb.2001.1589 Retrieved from http://bit.ly/1PTDyoC
Spielberg, C. D., & Díaz-Guerrero, R. (1975). IDARE. Inventario de Ansiedad: Rasgo-Estado. Ciudad de México: Manual Moderno.
Torres-Castillo, M., Hernández, E. & Ortega-Soto, H. (1991, jun). Validez y reproducibilidad del Inventario para Depresión de Beck en un hospital de cardiología. Salud Mental, 14(2), 1-6. Recuperado de http://bit.ly/1d4PiCW
Wood, W. F. (Dec, 2003). Volatile components in metatarsal glands of sika deer, Cervus nippon. Journal of Chemical Ecology, 29(12), 2729-2733. doi: 10.1023/B:JOEC.0000008016.44795.8ª Retrieved from http://bit.ly/1FSEva4
Woodward, S. L., Thompson, M. E., & Gangestad, S. W. (Jan, 2015). Women exposed to the scents of fertile-phase and luteal-phase women: evaluative, competitive, and endocrine responses. Adaptive Human Behavior and Physiology. doi: 10.1007/s40750-014-0019-8 Retrieved from http://bit.ly/1JdmUuB
Xu, F., Schaefer, M., Kida, I., Schafer, J., Liu, N., Rothman, D. L., …, & Shepherd, G. M. (Sep, 2005). Simultaneous activation of mouse main and accessory olfactory bulbs by odors or pheromones. Journal of Comparative Neurology, 489(4), 491-500. doi: 10.1002/cne.20652 Retrieved from http://bit.ly/1EG6FQz