ReviewThe role of oxytocin in mating and pregnancy
Highlights
► This review discusses the role of oxytocin release during and after mating. ► Oxytocin is involved in human sexuality. ► Animal models showed that oxytocin is important for female reproduction. ► In rodents, oxytocin is also involved in the establishment of prolactin surges of pregnancy.
Introduction
In female mammals, reproduction is a complex process that includes many different components, from courtship and mating to pregnancy and lactation. Interestingly, many hormones play important roles in these different stages, serving different functions for each. Estrogen and progesterone are well-known players in all of these stages of reproduction. However, oxytocin (OT) also contributes in mating, pregnancy and lactation. The present review will discuss research that emphasizes the role of OT on mating and the initiation of pregnancy.
OT secretions are of two types; OT is released centrally within the brain and into the periphery via the posterior pituitary. Within the brain, OT is produced mainly by two hypothalamic areas: (1) the parvocellular neurons of the paraventricular nucleus (PVN), the axons of which project to the posterior pituitary as well as other brain regions such as the brainstem and spinal cord, and (2) the magnocellular neurons within both the supraoptic nucleus (SON) and a subregion of the PVN, which possesses a large number of dendrites that release OT from vesicles into the extracellular space. OT-producing neurons have both autocrine and paracrine functions (Douglas and Meddle, 2008). OT is released in the brain in large amounts from the dendrites and soma of the magnocellular neurons, a process regulated independently from axonal release (Leng et al., 2008). The two types of release seem to be independently controlled and may play different roles (Neumann, 2007). Indeed, dendritic release is less dependent on electrical activity than axonal OT release than on intracellular calcium concentrations (Sabatier, 2006). Furthermore, the timing of the central and peripheral releases is not necessarily synchronized (Leng et al., 2008). The timing, control and roles of the two types of OT release are usually investigated independently. So far, few studies have clarified the combined roles of these two types of release in response to stimuli. Another intriguing aspect of OT is the fact that some brain areas rich in OT receptor expression may have very few OT axonal projections. This could be explained by dendritic and somatic releasing capacities which provide a paracrine signaling capable of diffusing far away from the releasing site to activate distant OT receptors. This dissociation also suggests that at least in part, OT action in the brain results from its neurohormonal capacity.
OT actions seem to be mediated by single receptors (Breton and Zingg, 1997) that demonstrate a species-specific expression. In the brain, the receptor was first described in rats using receptor autoradiography (Freund-Mercier et al. 1987). To our knowledge only one study has described OT receptor distribution in the human brain. Loup et al. (1991) used autoradiography and detected OT-binding sites in the basal nucleus of Meynert, the diagonal band of Broca, the lateral septal nucleus, the preoptic/anterior hypothalamus, the ventral pallidum and the lateral septum. This study, performed on 12 human subjects, did not discover any evidence of OT receptor expression in the striatum or the amygdala. Extensive research has allowed for a better understanding of the receptor distribution in rodents, particularly in rats, mice and voles. Interestingly, the high variability of expression is seen even among these close relatives. There are some brain regions where the receptor's expression is conserved between these three species such as in the lateral septal nucleus, where it is also seen in humans (Gimpl and Fahrenholz, 2001, Young and Zingg, 2009). OT binding activity in the bed nucleus of the stria terminalis (BNST), the central nucleus of the amygdala, and the ventromedial hypothalamus (VMH) has been found in these rodent relatives, but not yet in humans (Gimpl and Fahrenholz, 2001, Young and Zingg, 2009). In contrast, the striatum shows abundant binding in the prairie vole, partial binding in the rat, and none in the mouse (Young and Zingg, 2009). This species specific expression is associated with variations in mating and social behaviors. Furthermore, there is differential species-specific steroid-modulation in many brain areas which have also been shown to be influenced by maternal care received during development (Champagne et al., 2001). Evidently, these results emphasize the difficulty of extrapolating findings from animal studies to humans.
Very little is known about OT's role in human sexuality and reproduction. Although the hormone has been highlighted in the popular press, where it has been called the “love hormone,” research findings demonstrating its contribution to human love, particularly centrally, are very limited. However, in the periphery its activity may be responsible for increasing arousal through receptors, some of which are located in sexual organs. Research using animal models such as rats and non-human primates has revealed both peripheral and central release during and after mating as well as during pregnancy, which may help to clarify its role. Here we will argue that the effects of OT in mating are still mysterious and are more likely to be peripheral than central. To date, modulation of prolactin during pregnancy is OT's best-understood role in reproduction. In this review we will first summarize the results of studies investigating OT involvement in human sexuality. Secondly, we will discuss research findings using animal models suggesting peripheral and central OT contributions in mating in females and in the establishment of pregnancy.
Section snippets
Humans
While the role of OT in human reproduction still requires further elucidation, it does appear to be involved at both central and systemic levels. fMRI studies have reported activation of OT receptor-rich areas of the brain after orgasm and after presentation of visual stimuli of a loved one (Bartels and Zeki, 2000). However, to date, research on the role of OT in human reproduction has mainly concentrated on the periphery. OT has been clearly implicated in the contraction of male and female
Animal models
It has been shown that OT is released in the brain, where it is involved in the display of lordosis behavior (see review Ferri-Kolwicz and Flanagan-Cato, this issue) and the prolactin surges of pregnancy in the female (Arey and Freeman, 1989, Arey and Freeman, 1992, Egli et al., 2004). Though the function of OT in the central nervous system is becoming clearer, the role for peripheral OT release during mating in the female remains poorly understood. Neurons in the SON and the PVN release
Role of oxytocin in pregnancy
In rodents, VCS is sufficient to activate the neuroendocrine system, releasing the hormones involved in the initiation of pregnancy (Freeman et al., 1974). An important player in the initiation and maintenance of pregnancy is prolactin (see Egli et al., 2010 for review). In rodents, VCS during mating or mechanical stimulation induces the release of twice-daily surges of prolactin (Butcher et al., 1972, Smith and Neill, 1976) which are necessary for the rescue of the corpus luteum and the
Conclusions
Central roles for OT release during and after mating in females have been well identified in rodents. Animal models have helped clarify analgesic effects, and the memory of sexual partners in the rodent is well described. Researchers suspect an effect of OT on sexual satiety as well. At the level of the anterior pituitary gland, OT is also an important modulator of prolactin surges during pregnancy in rodents. Although the function of OT release into the periphery is not as well explained, it
Acknowledgments
We are grateful for Elizabeth Soehngen's contribution of ideas and for helping edit the manuscript.
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