Brain response to putative pheromones in lesbian women

Abstract

In animals, the choice of sexual partner is highly influenced by signals from sex-specific pheromones. These signals are processed by specific nuclei located in the anterior hypothalamus, identified as male and female mating centers (1–5). A lesion of the respective mating center as well as impairment of pheromone transduction may alter the coital approach in a sex-specific way (3–5). For example, electrolytic lesion of the preoptic area is reported to shift the mean preference of male ferrets away from the estrous females to the stud males (3, 5). Male rats are found to reduce their coital behavior after destruction of the preoptic area and show more interest in stimulus males than receptive females (1). Female ferrets, however, preferred females after destruction of the ventromedial hypothalamic nucleus (2) and did not allow males to intromit (4), whereas female rats increased the proportion of female approaches after kindling of the preoptic area (6).

In humans, reproductive functions are mediated by neuronal circuits of the anterior hypothalamus. There is reason to believe that these circuits also participate in the integration of the hormonal and sensory cues that are necessary for our sexual behavior and may also be involved in our sexual preferences (7). The preoptic area of the hypothalamus harbors cells releasing luteinic hormone-releasing hormone (8). These cells develop from the migrating neuroblasts of the olfactory mucosa (9) and mediate estrogen feedback. The estrogen feedback differs between males and females and also is reported to differ between homosexual men (HoM) and heterosexual men (HeM) (10). In addition, the anterior hypothalamus contains neuronal conglomerates (interstitial hypothalamic nuclei), of which two are reported to be sexually dimorphic in humans, and in a single study, one was found to differ in volume between HoM and HeM (10–13). A difference between HoM and HeM has also been found in the volume of suprachiasmatic nucleus (14).

In a previous positron emission tomography (PET) study of regional cerebral blood flow (rCBF) in heterosexual subjects, we found that smelling of two steroids, 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST), activated the anterior hypothalamus in a sex-differentiated manner (15). AND is a progesterone derivative detected in human sweat in concentrations that are ≈10 times higher in men compared with women (16). EST is an estrogen-like steroid that is detected in the urine of pregnant women (17). Both compounds are reported to induce sex-specific effects on the autonomic nervous system, mood, and context-dependent sexual arousal even without conscious perception (18–24), and both have been proposed as candidate compounds for human pheromones. Notwithstanding that the higher complexity of human behavior precludes direct extrapolations from the animal data to human biology, the colocalization of circuits processing signals from the two putative pheromones with the regions mediating mating behavior raises the question about a possible involvement of these same circuits in the physiology of human sexuality and sexual orientation. This issue is further emphasized by recent findings from HoM. Like heterosexual women (HeW) but unlike HeM, HoM activated the preoptic and ventromedial hypothalamic nuclei when smelling AND (25) but the classical olfactory regions (the amygdala, the piriform cortex, and the anterior insular cortex) (26–32) when smelling EST. The pattern of activation was reciprocal in HeM. Notably, signals from common odorants, such as cedar oil and lavender oil, were processed by the classical olfactory regions in HeM as well as in HoM and HeW (25).

Very little is currently known about the physiology of female homosexuality. However, if the chemosensory processing of AND and EST is related to sexual orientation rather than the biological sex, the pattern of activation in lesbian women would be expected to deviate from that of HeW. To investigate this hypothesis, PET experiments were carried out with measurements of rCBF in 12 lesbian women while they smelled AND, EST, and four ordinary odors (OO). Smelling of odorless air (denoted below as AIR) served as the base-line condition, and activations were defined as increases in rCBF during smelling of AND, EST, and OO in relation to air. The experimental design was identical to that of our previous study (25), and the results were compared with the previously generated data from HeM and HeW (25).

Activations were calculated with a one-group random-effect analysis (SPM99). Talairach coordinates indicate local maxima. Bold text indicates a significant cluster at T = 0.001 (corrected P < 0.05); the areas covered by the respective cluster are indicated. Regular text indicates a significant cluster at T = 0.01 (corrected P < 0.05). Italic text indicates a cluster at T = 0.01 (corrected P < 0.1). The clusters calculated at T = 0.01 were included to illustrate that the distribution of activations of the olfactory circuits during smelling of the two steroids was similar in the three groups.

Activations shared by the respective groups were calculated with conjunctional analysis (SPM99). Talairach coordinates indicate local maxima. Calculations at T = 0.001 are shown (corrected P < 0.05; *, corrected P = 0.06).

LH, luteinizing hormone; FSH, follicle-stimulating hormone.

Acknowledgments

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