Review
Sexual differentiation of pheromone processing: Links to male-typical mating behavior and partner preference

https://doi.org/10.1016/j.yhbeh.2009.02.008Get rights and content

Abstract

Phoenix et al. (Phoenix, C., Goy, R., Gerall, A., Young, W., 1959. Organizing actions of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 65, 369–382.) were the first to propose an essential role of fetal testosterone exposure in the sexual differentiation of the capacity of mammals to display male-typical mating behavior. In one experiment control male and female guinea pigs as well as females given fetal testosterone actually showed equivalent levels of mounting behavior when gonadectomized and given ovarian steroids prior to adult tests with a stimulus female. This finding is discussed in the context of a recent, high-profile paper by Kimchi et al. (Kimchi, T., Xu, J., Dulac, C., 2007. A functional circuit underlying male sexual behaviour in the female mouse brain. Nature 448, 1009–1014.) arguing that female rodents possess the circuits that control the expression of male-typical mating behavior and that their function is normally suppressed in this sex by pheromonal inputs that are processed via the vomeronasal organ (VNO)-accessory olfactory nervous system. In another Phoenix et al. experiment, significantly more mounting behavior was observed in male guinea pigs and in females given fetal testosterone than in control females following adult gonadectomy and treatment with testosterone. Literature is reviewed that attempts to link sex differences in the anatomy and function of the accessory versus the main olfactory projections to the amygdala and hypothalamus to parallel sex differences in courtship behaviors, including sex partner preference, as well as the capacity to display mounting behavior.

Introduction

In their classic paper Phoenix et al. (1959) reported the results of 4 experiments that transformed our thinking about the mechanism controlling the development of sex differences in the capacity of rodent species (in this case, guinea pigs) to display sex-appropriate mating behaviors. Experiments 1 and 2 showed that administering testosterone propionate (TP) to pregnant guinea pigs reduced (defeminized) the capacity of their female offspring to show lordosis responses to manual (human) flank stimulation later in life following ovariectomy and injections of estradiol and progesterone. Phoenix et al. took the bold step (for 1959) of speculating in their Discussion that “An assumption seldom made explicit is that modification of behavior follows an alteration in the structure or function of the neural correlates of the behavior. We are assuming that testosterone or some metabolites act on these central nervous tissues in which patterns of sexual behavior are organized.” My assignment in this essay is to link the organizational changes in aspects of sexual behavior resulting from fetal exposure to TP to changes in the neural processing and actions of socially relevant olfactory cues (‘pheromones’). All of the lordosis responses studied by Phoenix et al. were triggered by manual flank stimulation from a human hand. Thus it seems unlikely that either the sex difference in lordosis responsiveness or the defeminizing actions of fetal TP on females' lordosis behavior can be attributed to organizational actions of androgen on neural circuits that convey pheromonal inputs to parts of the brain that control lordosis behavior. Instead, the defeminizing effect of fetal androgen on subjects' lordosis capacity more likely reflects a change in the neural responsiveness to ovarian steroids and/or in the processing of somatosensory inputs to the hypothalamus derived from manual flank stimulation.

Phoenix et al. also reported that fetal exposure to TP enhanced female guinea pigs' capacity to display male-typical mounting behavior during tests given in adulthood. In Experiment 1 Phoenix et al. compared mounting behavior by gonadectomized subjects directed towards other male or female subjects during tests of lordosis behavior. When gonadectomized subjects were tested in the absence of adult hormone treatments only control males and females given TP fetally in doses/times that induced genital masculinization later displayed mounting; this behavior was not seen in control females or in females given TP fetally in doses/times that failed to masculinize the genitals. Interestingly, when these same groups of gonadectomized guinea pigs were treated in adulthood with estradiol and progesterone, control males and females as well as females given TP fetally displayed equivalent numbers of mounts directed towards the conspecifics used in lordosis testing. This latter observation is interesting in light of a recent proposal (Kimchi et al., 2007) that the circuitry controlling male-typical mating behavior lies dormant in the female rodent's brain, with its function only being revealed when the female is deprived of pheromonal signaling following the disabling of vomeronasal organ (VNO) inputs to the olfactory nervous system (more on this below). In Experiment 3 Phoenix et al. reported that adult treatment of gonadectomized subjects with TP stimulated appreciable mounting behavior in control males and in females given fetal TP in doses/times that induced genital masculinization, with significantly less mounting being shown by control females. In Experiment 4 perinatal exposure to exogenous TP failed either to disrupt or enhance the capacity of male guinea pigs to display male-typical sexual behavior in adulthood (comparisons were made with untreated control males). Although details are missing from the Methods section of Phoenix et al., I presume that the mounting behavior shown by subjects in their experiments was directed towards stimulus females that had been ovariectomized and primed with ovarian hormones so as to make them both attractive to conspecifics as well as receptive when mounted. There is now a substantial body of literature for rodent species that links male-typical attraction to estrous females as well as the male-typical capacity to display mounting and other male sex behaviors to male-typical anatomical and functional attributes of the main as well as accessory olfactory projections to the medial amygdala (Me) and the bed nucleus of the stria terminalis (BNST) as well as subnuclei of the hypothalamus, including the medial preoptic area (mPOA) and ventromedial hypothalamic nucleus (VMN). Phoenix et al. hinted at this forthcoming body of neuroscience research (to be reviewed, below) when they stated that “…the existence of a bisexuality is assumed. We suggest, however, that in the adult this bisexuality is unequal in the neural tissues as it is in the case of the genital tissues.”

Section snippets

The two olfactory nervous systems in mammals

Until recently, it was widely believed that pheromones that influence sexual attraction as well as mating behavior are exclusively detected in terrestrial vertebrates by the VNO, which is housed in a cartilaginous sheath in the roof of the mouth (Fig. 1). Pheromonal odorants, dissolved in nasal mucus, are actively pumped into the lumen of the VNO (Meredith and O'Connell, 1979) where they stimulate electrical activity in sensory neurons which express two different families of G-protein linked

Display of male-typical mating behavior in both sexes

A critical result of Phoenix et al. (1959) was that male guinea pigs, like females exposed to testosterone during fetal life, later showed significantly higher levels of mounting behavior than control females after all subjects had been gonadectomized and treated chronically with TP in adulthood. It must be noted; however, that under these circumstances even control females showed a low level of mounting behavior in tests with other receptive females. These behavioral results are consistent

Role of sexually dimorphic VNO-accessory olfactory signaling in the control of male-typical courtship and mating behaviors

Early work of Gorski et al. (1978) established that the volume of a sub-nucleus of the rat mPOA is sexually dimorphic—with the nucleus being 3–4 times larger in males than in females. Subsequent work of McCarthy et al. (Amateau et al., 2004, Amateau and McCarthy, 2002, Amateau and McCarthy, 2004) showed that the proliferation of dendritic spines on mPOA neurons is greater in male than in female rats as a result of a signaling cascade that begins with estradiol, formed neonatally in the male

Role of sexually dimorphic main olfactory system signaling in the control of male-typical courtship and mating behaviors

In contrast to the case of VNO sensory neurons, there is no evidence that sensory neurons in the MOE are sexually dimorphic in any manner. These OSNs project to glomeruli in the MOB which, in turn, are innervated by abutting mitral cells that extend axons mainly to the olfactory cortex. It addition, it has been known for some time (Davis et al., 1978, Scalia and Winans, 1975) that a subset of MOB mitral cells project to targets in the posterolateral cortical nucleus (PLCN) and anterior cortical

Acknowledgments

Preparation of this review was supported by NIH grant HD 044897. I thank Joe Oberlander and two anonymous referees for helpful comments on the manuscript.

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