Human Pheromones: Linking Neuroendocrinology and Ethology (revisited) International Society for Human Ethology, 2010 James V. Kohl Clinical Laboratory Scientist ASCP, ASCLS, AMT

Kohl, Atzmueller, Fink, Grammer (2001) Human Pheromones: integrating neuroendocrinology and ethology. Neuroendocrinology Letters 22(5): Adapted for presentation from: and Kohl (2007) The Mind's Eyes: human pheromones, neuroscience, and male sexual preferences Journal of Psychology & Human Sexuality, 18(4): Concurrently published in the Handbook of the Evolution of Human Sexuality Guest editor: Michael R. Kauth Editor: Eli Coleman. Taylor and Francis, Inc.

Support for the concept: Kohl, Kelahan, Hoffmann (2009) Human pheromones increase women's observed flirtatious behaviors and ratings of attraction 13th Annual Meeting of the Society for Behavioral Neuroendocrinology. East Lansing, Michigan.

Linking neuroendocrinology and ethology Neuroendocrinology: the study of the interactions between the nervous system and the endocrine system. Ethology: the scientific study of animal behavior. “The interaction between sensory input and hormonal levels appears to be a general rule in endocrine relationships underlying behavior.” (LeMagnen,1982) In other words: Sensory input effects hormones that affect behavior.

What are Pheromones? Pheromones are species specific sensory input from the social environment that influence “…a definite behavior or a developmental process.” Karlson & Luscher (1959) Pheromones': a new term for a class of biologically active substances. Nature Jan 3;183(4653):55-6. [e.g., by causing changes in levels of hormones]

Levels of Biological Organization Subatomic Particles; Atoms; Small Molecules; Macromolecules; Subatomic Particles; Atoms; Small Molecules; Macromolecules; Molecular Assemblies; (e.g., genes ) Organelle Molecular Assemblies; (e.g., genes ) Organelle Cell Cell Tissue Tissue Organ Organ Organ system Organ system Organism Organism Population; Species ; Community; Ecosystem; Biosphere Population; Species ; Community; Ecosystem; Biosphere

Sexual differentiation (Naftolin, 1981) This gene-cell-tissue-organ-organ system pathway allows natural selection to proceed at a pace and in directions keyed to environmental cues, like food odors and pheromones. The Gonads-Hormones-Behavior (G-H-B) model: A few genes cause gonadal differentiation and the gonadal hormones are responsible for the more widespread and contemporary aspects of structural development and function in the brain and body.

Gene-cell-tissue-organ-organ system In the G-H-B model, mammalian pheromones activate gene expression in gonadotropin releasing hormone (GnRH)-secreting nerve cells of tissue in the medial preoptic area of the anterior hypothalamus, which is the area of the brain that modulates the hypothalamic GnRH pulse. The brain is the most important organ of any organ system involved in behavior.

Pheromones effect hormones and control sexual behaviors The effect of pheromones on reproductive hormone status is mediated by GnRH neurons. GnRH plays an important role in the “control of sexual behaviors” via their link to reproductive hormone status [e.g., testosterone and estradiol] and sexual behavior that involves GnRH neurons. Boehm, U., Zou, Z., & Buck, L.B. (2005). Feedback loops link odor and pheromone signaling with reproduction. Cell, 123, Pheromones “control” definite behaviors by causing changes in levels of hormones. Shepherd, G. M. (2006). Behaviour: Smells, brains, and hormones. Nature, 439,

Sex differences in behavior (Naftolin, 1981) Complex and highly variable social factors in humans often obscure the exact mechanisms of events [that cause sex differences in behavior]. However, see Mak et al, (2007): Neurons in the olfactory bulb that express GnRH receive signals from pheromones and send projections to the hypothalamus, which results in the release of luteinizing hormone (LH) and follicular-stimulating hormone (FSH) by the anterior pituitary. Together, LH and FSH control the release of steroid hormones, such as estrogen, that influence sexual behavior…. (i.e., in the G-H-B model)

Nature SEXUAL DIFFERENTIATION PRENATAL PRE- and POSTNATAL GnRH Nerve cell Migration Olfactory placode Olfactory Bulbs Limbic System Hypothalamic GnRH Hypothalamus GnRH pulse frequency and amplitude extrapituitary effects Pituitary LH / FSH HPG axis HPA axis Adrenal metabolites (androsterone) (etiocholanolone) FSHLH Gonads Testes (androgenic metabolites) Ovaries (estrogenic metabolites) Adrenals Pheromones PHEROMONESPHEROMONES Synaptogenesis Synaptolysis Apoptosis Synaptogenesis Synaptolysis Apoptosis NEUROTRANSMISSION CyclicTonic MaleFemale Neuronal feedback PositiveNegative Aging Sexual Expression Sexual Identity Sexual orientation Learning and Memory Pheromones alter GnRH-modulated: neural circuitry, odor hedonics, mood, memory, motivation, cognitive behavioral state, and potentiating responses to other stimuli, and link Nature to Nurture via affective reactions Nurture The influence of pheromones from the same sex or from the opposite sex on postnatal sexual differentiation Pheromones From the same sex From the opposite sex Extrahypothalamic GnRH Luteinizing Hormone: The link between sex and the sense of smell

Hypothalamus Medial preoptic area of the anterior hypothalamus MPOA/AH MP-AHN Sexual preference difference (1)

Pheromones, GnRH, other Hormones and Behavior One central neuronal (i.e., GnRH) pathway links: noradrenergic, dopaminergic, serotoninergic, and opiodergic pathways, as well as inhibitory neurotransmitters like gamma­aminobutyric acid and excitatory amino acids like glutamic and aspartic acids and other brain peptides including pineal secretions like melatonin and corticotrophin­releasing hormone and the complex interactions among them (e.g., the effects of hormones)… …to functional species-specific influences, which are linked to behavioral affect by the same hormone-secreting cells, that pheromones directly effect.

Pheromones and the hypothalamic GnRH pulse GnRH modulates the concurrent maturation of the neuroendocrine system, the reproductive system and the central nervous system. GnRH is required for LH release Increased GnRH pulse frequency favors LH release. The opposite sex pheromones of other mammals cause LH release. Axillary pheromones of men cause LH and mood change in women

Prepubertal conditioning "There is now ample evidence that GnRH is secreted episodically in the prepubertal child long before physical signs of puberty appear (Jakacki et al., 1982). The onset of puberty therefore appears to be associated with an amplification of pulsatile gonadotropin secretion.” Hopwood, N.J., Kelch, R.P., Hale, P.M., Mendes, T.M., Foster, C.M., & Beitins. I.Z. (1990) The onset of puberty: biological and environmental factors. In: Bancroft, J, & Reinisch, J.M. (eds.) Adolescence and Puberty. (pages 29 ‑ 49) New York: Oxford University Press.

The neuroendocrinology of diverse sexual preferences Unconditioned stimulus (UCS): Pheromones Conditioned stimulus (CS): visual, auditory, tactile, gustatory—combined? The CS (e.g., visual input), gains behavioral significance after being paired with a biologically active UCS (e.g., pheromones). Odors/pheromones are the proximate cause Hormone-driven preferences are their effect.

Affective primacy 1.Positive and negative affective reactions can be evoked with minimal stimulus input and virtually no cognitive processing. 2.Affect dominates social interaction and it is the major currency in social interactions 3.Affective reactions can occur without extensive perceptual and cognitive encoding. They are made with greater confidence than cognitive judgments, and can be made sooner.

Affective primacy is Olfactory primacy Olfactory input from the social environment fits the assertions of affective primacy. For example, chemical cues allow humans to select for, and to mate for, traits of reproductive fitness that cannot be assessed simply from visual cues. The affect of pheromones on our emotions is linked to the effect of pheromones on the hormones of the hypothalamic-pituitary- gonadal axis – an unconscious affect.

Affect, olfactory primacy, and other sensory input Affect is conditioned in the presence of other sensory input. Mammalian neuroanatomical pathways link vision and olfaction. Cooper et al. (1994)

Conditioning the response to visual stimuli (in rats) Social-environmental odor cues, which males learn to visually associate with sexual activity, can be used to condition LH release. After minimal conditioning, an arbitrary odor ultimately will elicit a male LH response, even in the absence of odor previously associated with a female. Regardless of whatever other sensory input (e.g., visual input) is involved, the functional significance of the conditioned change in LH secretion lies principally in the unequivocal demonstration that olfactory cues can activate the male hypothalamic-pituitary-gonadal axis in a way that mimics, in every respect, the activation achieved by exposure to a female. Graham & Desjardins (1980)

High Estrogen/Androgen ratios, physical features… Feminine features: small jaw, full lips, large breasts, narrow waist, shorter, higher vocal pitch, light complexion, etc. …AND THE PHEROMONES OF WOMEN.

Low Estrogen/Androgen ratios, physical features… Masculine features: growth of the jaw, brow ridges, center of the face from the brow to the bottom of the nose, more facial hair, taller, darker, more muscular, etc. …AND THE PHEROMONES OF MEN.

Hormone-dependent features Used with permission from Victor Johnson

J.V. Kohl; L.C. Kelahan; H. Hoffmann HUMAN PHEROMONES INCREASE WOMEN’S OBSERVED FLIRTATIOUS BEHAVIORS AND RATINGS OF ATTRACTION. Conclusions: The known effect of androstenol on luteinizing hormone in women and what appears to be an associated behavioral affect of androsterone meet criteria that characterize human pheromones. Kelahan-testing and results; Hoffmann-professorship; Kohl-study design Poster session:

Terms of Endeerment “[Cindy]... had gone alone to a portable commode hidden in a thicket to change her tampon, unaware that a young stag was nearby... Smelling her [natural] secretions, [the male deer] became sexually aroused. He bounded through the trees and knocked Cindy to the ground. Then while prancing up and down with his forefoot on her shoulder, the sexually excited deer sprinkled her with semen." Gibbons, D.L. (1989) Unusual case: Sex in the woods. Medical Aspects of Human Sexuality, 23, 10(Oct), 63.

Sexual Odors / Food Odors “It is important to remember that the animal perceives erotic odors in a manner analogous to his perception of food odors.” Bloch, I. (1933) Odoratus Sexualis: A Scientific and Literary Study of Sexual Scents and Erotic Perfumes. New York: American Anthropol. Soc.