Neil V. Watson

Pre- and postnatal bisphenol A treatment results in persistent deficits in the sexual behavior of male rats, but not female rats, in adulthood.

Perinatal administration of the endocrine disruptor bisphenol A (BPA) reportedly inhibits the sexual behavior of sexually naïve adult male rats. In order to evaluate the effects of BPA administration during early development on later reproductive behavior, we administered one of five doses of bisphenol A daily to pregnant female rats throughout gestation and lactation, and quantified the appetitive and consummatory sexual behaviors of the resultant male and female offspring over multiple sexual encounters in adulthood. Males receiving low dose perinatal BPA (50 μg/kg bw/day) showed persistent deficits in sexual behavior in adulthood. Males receiving the highest dose (5 mg/kg bw/day), however, were indistinguishable from controls with respect to consummatory sexual behaviors but showed decreased latencies to engage in those behaviors when sexually naïve, with significant non-linear, or U-shaped, dose-response relationships observed on the first and last day of testing. Adult female sexual behavior was not affected by early BPA administration at any dose tested. These results are consistent with previous reports that BPA exerts behavioral effects especially at low doses, and further indicates that BPA can cause lasting impairment of sexual behavior in males, but does not alter the normal development of female appetitive or consummatory sexual behaviors. To our knowledge, this is the first report indicating that adult sexual performance is impaired in sexually experienced animals following perinatal exposure to bisphenol A.

Social neuroendocrinology : Effects of social contexts and behaviors on sex steroids in humans.

In this paper we provide a critical review of research concerned with social/environmental mechanisms that modulate human neuroendocrine function. We survey research in four behavioral systems that have been shaped through evolution: competition, partnering, sex, and pregnancy/parenting. Generally, behavioral neuroendocrine research examines how hormones affect behavior. Instead, we focus on approaches that emphasize the effects of behavioral states on hormones (i.e., the “reverse relationship”), and their functional significance. We focus on androgens and estrogens because of their relevance to sexually selected traits. We conclude that the body of research employing a reversed or bidirectional perspective has an incomplete foundation: participants are mainly heterosexual men, and the functionality of induced shifts in neuroendocrine factors is generally unknown. This area of research is in its infancy, and opportunities abound for developing and testing intriguing research questions.

Relationship status and testosterone in North American heterosexual and non-heterosexual men and women : Cross-sectional and longitudinal data

Previous research has found that single heterosexual (Het) men have higher salivary testosterone (T) concentrations than partnered Het men. Here, we used both longitudinal and cross-sectional analyses to examine a more diverse population (n = 258) that included Het and non-heterosexual (Non-Het) women and men. Results showed that, for Het men (but not Het women) and Non-Het women (but not Non-Het men), baseline T was significantly lower in partnered than unpartnered individuals. Longitudinal analyses indicated that changes in partnered status were not associated with changes in testosterone concentrations; instead, women and men with lower T at baseline were significantly more likely to be partnered at follow-up. These findings thus suggest that partnered status is associated with stable, trait-level T values, rather than current state. Furthermore, the observed effect is limited to individuals (male or female) who are oriented toward female partners. The results are discussed in terms of evolutionary trade-offs between single and multiple partners, and the possibility of female choice and/or disinterest.

Associations between testosterone secretion and sexual activity in women

Some studies show an increase in testosterone (T) after sexual activity; this literature has inconsistent findings, focuses mostly on men, and does not employ control activities. The present study examined within-subject effects of intercourse versus control activities (cuddling; exercise) on salivary T. The initial sample included 49 women (mostly heterosexual), though not all participants returned all samples or engaged in all activities, leaving a smaller sample for endocrine analyses (n=16). Participants attended an initial session in the laboratory where they completed questionnaires, and then engaged in the activities on their own. On three separate nights, they provided pre-activity, post-activity, and next-morning saliva samples and completed brief questionnaires at the last two timepoints. Womens T was higher pre-intercourse than pre-control activity. Womens T was also higher post-intercourse than post-control activity, though the percent change in T from pre- to post-activity was highest for cuddling, then intercourse, then exercise. Next-morning T did not differ by activity. Data pointed to an association between T and orgasming, sexual desire, and relationship commitment. Analyses on post-activity appraisals suggest that the close intimate physicality of a sexual and non-sexual nature can affect T and be beneficial in short-term and perhaps longer-lasting ways for womens sexuality and relationships.

Testosterone levels in women and men who are single, in long-distance relationships, or same-city relationships

Research points to an association between testosterone (T) and partnering in some women and men, and this association has been interpreted as an effect of either relationship status (i.e. differences in relationship status lead to differences in T) or relationship orientation (i.e. T is associated with the likelihood of entering relationships). To address whether physical partner presence was associated with decreased T, we examined T levels in people (72 women; 49 men) who were single, in long-distance relationships, or in same-city relationships. No participants were using exogenous hormones, including hormonal contraceptives. Participants provided a saliva sample and responded to questions about their relationship status. Single men had higher T than long-distance and same-city partnered men, which supports the relationship orientation interpretation. In contrast, same-city partnered women had lower T than single women and women in long-distance relationships, which supports the relationship status interpretation. We conclude that physical partner presence is not necessary to see an association between partnering and hormones in men (since same-city and long-distance partnered men had similar T levels), but may be necessary in women (since same-city partnered women had lower T than long-distance partnered women).

Androgens Increase Survival of Adult-Born Neurons in the Dentate Gyrus by an Androgen Receptor-Dependent Mechanism in Male Rats

Gonadal steroids are potent regulators of adult neurogenesis. We previously reported that androgens, such as testosterone (T) and dihydrotestosterone (DHT), but not estradiol, increased the survival of new neurons in the dentate gyrus of the male rat. These results suggest androgens regulate hippocampal neurogenesis via the androgen receptor (AR). To test this supposition, we examined the role of ARs in hippocampal neurogenesis using 2 different approaches. In experiment 1, we examined neurogenesis in male rats insensitive to androgens due to a naturally occurring mutation in the gene encoding the AR (termed testicular feminization mutation) compared with wild-type males. In experiment 2, we injected the AR antagonist, flutamide, into castrated male rats and compared neurogenesis levels in the dentate gyrus of DHT and oil-treated controls. In experiment 1, chronic T increased hippocampal neurogenesis in wild-type males but not in androgen-insensitive testicular feminization mutation males. In experiment 2, DHT increased hippocampal neurogenesis via cell survival, an effect that was blocked by concurrent treatment with flutamide. DHT, however, did not affect cell proliferation. Interestingly, cells expressing doublecortin, a marker of immature neurons, did not colabel with ARs in the dentate gyrus, but ARs were robustly expressed in other regions of the hippocampus. Together these studies provide complementary evidence that androgens regulate adult neurogenesis in the hippocampus via the AR but at a site other than the dentate gyrus. Understanding where in the brain androgens act to increase the survival of new neurons in the adult brain may have implications for neurodegenerative disorders.

Distribution of androgen receptor immunoreactivity in the brainstem of male rats

Gonadal steroids such as testosterone and estrogen are necessary for the normal activation of male rat sexual behavior. The medial preoptic area (MPOA), an important neural substrate regulating mating, accumulates steroids and also expresses functional androgen receptors (AR). The MPOA is intimately connected with other regions implicated in copulation, such as the bed nucleus of the stria terminalis and medial amygdala. Inputs to the MPOA arise from several areas within the brainstem, synapsing preferentially onto steroid sensitive MPOA cells which are activated during sexual activity. Given that little is known about the distribution of AR protein in the brainstem of male rats, we mapped the distribution of AR expressing cells in the pons and medulla using immunocytochemistry. In agreement with previous reports, AR immunoreactivity (AR-ir) was detected in ventral spinal motoneurons and interneurons. In addition, AR-ir was detected in areas corresponding to the solitary tract, lateral paragigantocellular and alpha and ventral divisions of the gigantocellular reticular nuclei, area postrema, raphe pallidus, ambiguus nucleus, and intermediate reticular nucleus. Several regions within the pons contained AR-ir, such as the tegmental and central gray, parabrachial nucleus, locus coeruleus, Barringtons nucleus, periaqueductal gray, and dorsal raphe. In contrast with in situ hybridization studies, auditory and somatosensory areas were AR-ir negative, and, except for very light staining in the prepositus nucleus, areas carrying vestibular information did not display AR-ir. Additionally, cranial nerve motoneurons of the hypoglossal, facial, dorsal vagus, and spinal trigeminal did not display AR-ir in contrast to previous reports. The data presented here indicate that androgens may influence numerous cell groups within the brainstem. Some of these probably constitute a steroid sensitive circuit linking the MPOA to motoneurons in the spinal cord via androgen responsive cells in the caudal ventral medulla.

Spatial memory performance in androgen insensitive male rats.

Masculinization of the developing rodent brain critically depends on the process of aromatization of circulating testosterone (T) to its estrogenic metabolite 17beta-estradiol, which subsequently interacts with estrogen receptors to permanently masculinize the brain. However, it remains unclear what role other androgenic mechanisms may play in the process of masculinization. A novel way of examining this is through the study of male rats that express the tfm mutation of the androgen receptor (AR) gene; such males are fully androgen insensitive and manifest a female phenotype due to a failure of AR-mediated masculinization of peripheral structures. Because tfm-affected males develop secretory testes and have near-normal T titers during development, aromatization would be expected to proceed normally, and brain mechanisms may be developmentally masculinized despite the feminized periphery. We compared tfm-affected males (X(tfm)Y) with normal males and females in the Morris Water Maze, a task in which males typically perform better than females. Performance of tfm-affected males was intermediate between that of normal males and females. While an overall male superiority was found in the task, the X(tfm)Y group reached male-typical escape latencies faster than females. Furthermore, in the X(tfm)Y group, the granule cell layer of the dentate gyrus was significantly larger than in females. These results support the suggestion that that AR mediated mechanisms contribute to the masculinization of spatial behaviours and hippocampal morphology, and this may be independent of estrogenic processes.

Perinatal BPA exposure demasculinizes males in measures of affect but has no effect on water maze learning in adulthood

Bisphenol A (BPA) is an endocrine disrupting agent that can alter the normal gonadal steroid-sensitive sexual differentiation of the brain and behavior. While reproductive behavior and physiology are known to be altered by perinatal exposure to this compound, less is known about BPAs effects on sex differences in learning and measures of affect. In order to evaluate the effects of perinatal BPA treatment on learning and affect in adulthood, we exposed rats to one of five doses of BPA through gestation and lactation then examined adult behavior in the Morris Water Maze (MWM), the Elevated Plus Maze (EPM) and the Forced Swim Test (FST). No effect of BPA was observed in the MWM, but on both the EPM and FST, low doses (5 μg/kg) of BPA eliminated sex differences found between controls; furthermore, a non-monotonic dose-response observed in previous studies was confirmed for these tasks. Overall, our study adds to the growing data suggesting that BPA interferes with the normal development of affective behaviors in a non-linear, dose-dependent manner.

Effects of ability- and chance-determined competition outcome on testosterone

Winning competitions has been shown to lead to higher testosterone (T) relative to losing in men and males of other species. In Experiment 1, 38 women and 37 men provided a saliva sample, completed a novel computer-based vocabulary competition task at which they won or lost based on their own ability, provided feedback about the competition via questionnaire, and then produced a second saliva sample. Task outcome and performance was not sexually differentiated, and overall task performance was negatively correlated with T. Male but not female winners had lower baseline and post-competition T, and male losers had a larger decrease in T from baseline to post-competition. In Experiment 2, 31 men and 43 women completed the same as above, but were randomly assigned to win or lose. In this case, competition outcome did not affect T for men but there was an effect such that women who would have had an ability-determined loss showed a larger decrease in T than women who would have had an ability-determined win. Thus, earned wins appear to attenuate a decline in T in men, consistent with past research into the competition effect and T, and perhaps women under complex circumstances.