Androgen Receptor Expression in Satellite Cells in the Levator Ani of the Rat

The sexual differentiation of the spinal nucleus of bulbocavernosus (SNB) and the bulbocavernosus (BC) and levator ani (LA) muscles that the SNB innervates, are masculinized by androgens acting on the BC/LA. The site of androgen receptors (AR) responsible for the masculinization of the neuromuscular system is not known. A potential site of action is satellite cells: proliferation of these cells is androgen-dependent and satellite cells seem to contribute to the size of the LA. Fluorescent immunohistochemistry and confocal microscopy were used to co-localize satellite cells and AR within the LA of postnatal day one and three male and female rats. Results indicate that satellite cells express AR and reveal a difference in proportion of satellite cells expressing AR between the LA and control muscle. Interpretations of these findings, including whether the relatively small proportion of AR accounted for by satellite cells is enough to masculinize the SNB system, are discussed.MAS

Non-neural and Neural Contributions of Androgen Receptors to Socio-sexual Behaviours in Mice

Sexual differentiation of the brain and behaviour is mediated in part by androgens acting on androgen receptors (AR), however it remains unclear whether differentiation is due to action on AR in neural and/or non-neural tissues. To evaluate the role of neural and non-neural AR on sexual differentiation, four experiments were conducted using two models of AR overexpression: neural versus global overexpression of AR. In Chapter 1, the theoretical framework for investigating non-neural contributions of androgens on the sexual differentiation of the nervous system and behaviour is evaluated. In Chapter 2, the transgenic models are characterized by confirming AR overexpression in neural tissue of both neural and global AR overexpression mice, and in a non-neural tissue of global, but not neural, overexpression mice. Next, transgenic mice and wildtype littermates are compared on measures of aggression, copulation and social investigation in response to a male and female stimulus animal. In Chapter 3, neural and global AR overexpression models are tested on an olfactory choice paradigm and neural activity in response to female odors is evaluated. In Chapter 4, the organizational and activational effects of sex hormones on male-typical preference for volatile and non-volatile female cues are assessed by manipulating gonadal hormones during the critical period of development and in adulthood in females. Lastly, in Chapter 5, the role of adult circulating androgens in male-typical preference for volatile and non-volatile female cues is examined in both global and neural AR overexpression males and wildtype littermates by gonadectomy and hormone replacement in adulthood. Together, results suggest that 1) there are distinct roles for both neural and non-neural AR on the organization and activation of male-typical behaviour, 2) that the underlying circuitry responsible for the activation of preference for female cues is present in females, and 3) a nonlinear relationship between AR and male-typical behaviour is proposed, such that AR signaling in either less than or in excess of the normal male range decreases male-typical behaviour.Ph.D

Turning sex inside-out: Peripheral contributions to sexual differentiation of the central nervous system

<p>Abstract</p> <p>Sexual differentiation of the nervous system occurs via the interplay of genetics, endocrinology and social experience through development. Much of the research into mechanisms of sexual differentiation has been driven by an implicit theoretical framework in which these causal factors act primarily and directly on sexually dimorphic neural populations within the central nervous system. This review will examine an alternative explanation by describing what is known about the role of peripheral structures and mechanisms (both neural and non-neural) in producing sex differences in the central nervous system. The focus of the review will be on experimental evidence obtained from studies of androgenic masculinization of the spinal nucleus of the bulbocavernosus, but other systems will also be considered.</p

Gender Nonconformity and Birth Order in Relation to Anal Sex Role Among Gay Men

This is an accepted manuscript published by Springer.Androphilia is associated with an elevated number of older brothers among natal males. This association, termed the fraternal birth order effect, has been observed among gay men who exhibit marked gender nonconformity. Gender nonconformity has been linked to gay men's preferred anal sex role. The present study investigated whether these two lines of research intersect by addressing whether the fraternal birth order effect was associated with both gender nonconformity and a receptive anal sex role (243 gay men, 91 heterosexual men). Consistent with previous research, we identified the fraternal birth order effect in our sample of gay men. Also, gay men were significantly more gender-nonconforming on adulthood and recalled childhood measures compared to heterosexual men. When gay men were compared based on anal sex role (i.e., top, versatile, bottom), all groups showed significantly greater recalled childhood and adult male gender nonconformity than heterosexual men, but bottoms were most nonconforming. Only gay men with a bottom anal sex role showed evidence of a fraternal birth order effect. A sororal birth order effect was found in our sample of gay men, driven by versatiles. No significant associations were found between fraternal birth order and gender nonconformity measures. These results suggest that the fraternal birth order effect may apply to a subset of gay men who have a bottom anal sex role preference and that this subgroup is more gender-nonconforming. However, there were no significant associations between fraternal birth order and gender nonconformity at the individual level. As such, based on the present study, whether processes underpinning the fraternal birth order effect influence gender nonconformity is equivocal.Natural Sciences and Engineering Research Council of Canada Discovery Grant awarded to DPV (RGPIN-2016-06446

Handedness is a biomarker of variation in anal sex role behavior and Recalled Childhood Gender Nonconformity among gay men

This is an accepted manuscript published by the Public Library of Science.Developmental theories of the biological basis of sexual orientation suggest that sexually differentiated psychological and behavioural traits should be linked with sexual orientation. Subgroups of gay men delineated by anal sex roles differ according to at least one such trait: gender expression. The present study assessed the hypothesis that handedness, a biologically determined sexually differentiated trait, corresponds to differences in subgroups of gay men based on anal sex role. Furthermore, it assessed whether handedness mediates the association between gender nonconformity and male sexual orientation. Straight and gay men (N = 333) completed the Edinburgh Inventory of Handedness and the Recalled Childhood Gender Nonconformity Scale. Gay men also completed measures of anal sex role preference. As in previous studies, gay men showed greater non-right-handedness and gender nonconformity than straight men. Also, among gay men, bottoms/versatiles (i.e., gay men who take a receptive anal sex role, or who take on both a receptive and insertive anal sex role) were more gender-nonconforming than tops (i.e., gay men who take an insertive anal sex role). In support of the hypothesis, bottoms/versatiles were more non-right-handed than tops and handedness mediated the male sexual orientation and anal sex role differences in Recalled Childhood Gender Nonconformity. Together, these findings suggest that developmental processes linked to handedness underpin variation among men in sexual orientation and gender nonconformity as well as variation among subgroups of gay men that are delineated by anal sex roles.The research reported in this article was supported by a doctoral Canadian graduate scholarship National Sciences and Engineering Research Council of Canada (NSERC; http://www.nserc-crsng.gc.ca) grant to ASG, and NSERC Discovery Grants to DAM (RGPIN-2016-06302) and DPV (RGPIN-2016-06446)

Removal of reproductive suppression reveals latent sex differences in brain steroid hormone receptors in naked mole-rats, Heterocephalus glaber

Abstract Background Naked mole-rats are eusocial mammals, living in large colonies with a single breeding female and 1–3 breeding males. Breeders are socially dominant, and only the breeders exhibit traditional sex differences in circulating gonadal steroid hormones and reproductive behaviors. Non-reproductive subordinates also fail to show sex differences in overall body size, external genital morphology, and non-reproductive behaviors. However, subordinates can transition to breeding status if removed from their colony and housed with an opposite-sex conspecific, suggesting the presence of latent sex differences. Here, we assessed the expression of steroid hormone receptor and aromatase messenger RNA (mRNA) in the brains of males and females as they transitioned in social and reproductive status. Methods We compared in-colony subordinates to opposite-sex subordinate pairs that were removed from their colony for either 1 day, 1 week, 1 month, or until they became breeders (i.e., produced a litter). Diencephalic tissue was collected and mRNA of androgen receptor (Ar), estrogen receptor alpha (Esr1), progesterone receptor (Pgr), and aromatase (Cyp19a1) was measured using qPCR. Testosterone, 17β-estradiol, and progesterone from serum were also measured. Results As early as 1 week post-removal, males exhibited increased diencephalic Ar mRNA and circulating testosterone, whereas females had increased Cyp19a1 mRNA in the diencephalon. At 1 month post-removal, females exhibited increased 17β-estradiol and progesterone. The largest changes in steroid hormone receptors were observed in breeders. Breeding females had a threefold increase in Cyp19a1 and fivefold increases in Esr1 and Pgr, whereas breeding males had reduced Pgr and increased Ar. Conclusions These data demonstrate that sex differences in circulating gonadal steroids and hypothalamic gene expression emerge weeks to months after subordinate animals are removed from reproductive suppression in their home colony

Evidence for distinct biodevelopmental influences on male sexual orientation

This is an accepted manuscript published by the National Academy of SciencesSeveral biological mechanisms have been proposed to influence male sexual orientation, but the extent to which these mechanisms cooccur is unclear. Putative markers of biological processes are often used to evaluate the biological basis of male sexual orientation, including fraternal birth order, handedness, and familiality of same-sex sexual orientation; these biomarkers are proxies for immunological, endocrine, and genetic mechanisms. Here, we used latent profile analysis (LPA) to assess whether these biomarkers cluster within the same individuals or are present in different subgroups of nonheterosexual men. LPA defined four profiles of men based on these biomarkers: 1) A subgroup who did not have these biomarkers, 2) fraternal birth order, 3) handedness, and 4) familiality. While the majority of both heterosexual and nonheterosexual men were grouped in the profile that did not have any biomarker, the three profiles associated with a biomarker were composed primarily of nonheterosexual men. We then evaluated whether these subgroups differed on measures of gender nonconformity and personality that reliably show male sexual orientation differences. The subgroup without biomarkers was the most gender-conforming whereas the fraternal birth order subgroup was the most female-typical and agreeable, compared with the other profiles. Together, these findings suggest there are multiple distinct biodevelopmental pathways influencing same-sex sexual orientation in men.Natural Sciences and Engineering Research Council of Canada Discovery Grant awarded to DPV (RGPIN-2016-06446)

Removal of reproductive suppression reveals latent sex differences in brain steroid hormone receptors in naked mole-rats, Heterocephalus glaber

This is an accepted manuscript published by BioMed Central.Naked mole-rats are eusocial mammals, living in large colonies with a single breeding female and 1–3 breeding males. Breeders are socially dominant, and only the breeders exhibit traditional sex differences in circulating gonadal steroid hormones and reproductive behaviors. Non-reproductive subordinates also fail to show sex differences in overall body size, external genital morphology, and non-reproductive behaviors. However, subordinates can transition to breeding status if removed from their colony and housed with an opposite-sex conspecific, suggesting the presence of latent sex differences. Here, we assessed the expression of steroid hormone receptor and aromatase messenger RNA (mRNA) in the brains of males and females as they transitioned in social and reproductive status.The research reported in this manuscript was supported by Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grants 312458 (DAM) and 402633 (MMH), a Connaught Foundation New Investigator award to MMH, a doctoral Canadian graduate scholarship (CGS) NSERC grant to ASG, and a doctoral Postgraduate scholarship (PGS) NSERC to DEP