Pheromone effects on the human hypothalamus in relation to sexual orientation and gender

Abstract

Pheromones are chemicals that serve communicational purposes within a species. In most terrestrial mammals, pheromones are detected by either the olfactory epithelium or the vomeronasal organ and processed by various downstream structures including the medial amygdala and the hypothalamus to regulate motivated behaviors and endocrine responses. The search for human pheromones began in the 1970s. Whereas bioactive ligands are yet to be identified, there has been accumulating evidence that human body odors exert a range of pheromone-like effects on the recipients, including triggering innate behavioral responses, modulating endocrine levels, signaling social information, and affecting mood and cognition. In parallel, results from recent brain imaging studies suggest that body odors evoke distinct neural responses from those observed with common nonsocial odors. Two endogenous steroids androsta-4,16,- dien-3-one and estra-1,3,5(10),16-tetraen-3-ol are considered by some as candidates for human sex pheromones. The two substances produce sexually dimorphic effects on human perception, mood, and physiological arousal. Moreover, they reportedly elicit different hypothalamic response patterns in manners contingent on the recipients’ sex and sexual orientation. Neuroendocrine mechanisms underlying the effects of human chemosignals are not yet clear and await future detailed analyses.

Introduction

Chemical communication is ubiquitous across the animal kingdom and has been shown in humans as well. In 1959, Karlson and Lüscher coined the term “pheromone” to refer to substances that are “secreted to the outside by an individual and received by a second individual of the same species, in which they release a specific reaction, for example, a definite behavior or a developmental process” (Karlson and Lüscher, 1959). Substances that elicit an immediate behavioral response are classified as releaser pheromones, whereas those that more slowly influence endocrine state or development are primer pheromones. In the same year, Butenandt discovered Bombykol or (E,Z)-10,12-hexadecadienol, which is released in minute amounts by female silkworms to attract mates. Bombykol was the first pheromone to be characterized chemically. Since then, a number of pheromones serving various communicational purposes have been identified in yeasts, bacteria, insects, fish, and mammals. They come in different chemical forms, from simple molecules like formic acid to more complex ones including steroids, peptides, and proteins (Kikuyama et al., 1995; Sorensen et al., 2005; Fujiwara-Tsujii et al., 2006). More often than not, pheromones are multicomponent, comprising different compounds in a specific ratio, and the components work in synergy (Greenwood et al., 2005). There are sex pheromones, aggregation pheromones, alarm pheromones, territorial pheromones, trail and recruitment pheromones, and so on. Some specific mammalian pheromonal effects include regulating sexual receptivity, accelerating puberty, suppressing pregnancy, modulating parental behavior, inducing stress, and conveying identity (Bruce, 1959; Colby and Vandenberg, 1974; Fleming et al., 1979; Dorries et al., 1997; Haga et al., 2010; Brechbuhl et al., 2013). It must be noted that these effects do not all fit into the original rigid definition of pheromone (e.g., the communication of identity). As more forms of intraspecific chemical communication have been identified, the term pheromone is now commonly used for chemical signals that convey information between members of the same species. Apart from releaser and primer pheromones, researchers recognize the category of signaler pheromones, those that convey information such as identity about the sender. In 2000, Jacob and McClintock, based on their work in humans, proposed a further category of modulator pheromones, which modulate the psychological state of the recipient (Jacob and McClintock, 2000). The roles of releaser, primer, signaler, and modulator are likely not mutually exclusive, for instance, two volatiles in male mouse urine dehydro-exo-brevicomin and 2-sec-butyl-4,5-dihydrothiazole have been found to exert both releaser and primer effects (Novotny, 2003).