Two sexually dimorphic cell groups in the human brain

Allen, LS; Hines, Melissa; Je, Shryne; Gorski, RA

doi:10.1523/jneurosci.09-02-00497.1989

Cited by 428 publications

(197 citation statements)

References 53 publications

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“…1). The INAH3 volume size and the presence of a sex difference in INAH3 volume size fully agreed with previously reported data (54,64,69,70), as did the sex difference for the number of neurons in INAH3. A number of different names have been used to refer to the two Un subnuclei (68): i) periventricular and uncinate nucleus (the former closer to the third ventricle than the latter) (61); ii) INAH4 (closer to the third ventricle than the INAH3) (64); and, most recently, iii) lateral and medial subdivisions of the Un (62).…”

Section: Sex Differences In the Human Brainsupporting

confidence: 91%

“…We found this nucleus to be 2.5 times larger in men than in women and to contain 2.2 times as many cells (63). Allen et al, (64) described four interstitial nuclei of the anterior hypothalamus (INAH1-4) and found, in men compared to women, a larger volume of the INAH3 and INAH2 subdivisions (respectively 2.8 and 2 times greater). The fact that they could not find a sex difference in INAH1 (= SDN-POA), as found by us (63), could be fully explained by the strong age effect on the sex differences of this nucleus (58,65).…”

Section: Sex Differences In the Human Brainmentioning

confidence: 45%

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Sexual differentiation of the human brain in relation to gender identity and sexual orientation

Savić

Garcı́a-Falgueras

Swaab

2010

Progress in Brain Research

125

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SummaryDuring the intrauterine period the fetal brain develops in the male direction through a direct action of testosterone on the developing nerve cells, or in the female direction through the absence of this hormone surge. In this way, our gender identity (the conviction of belonging to the male or female gender) and sexual orientation are programmed into our brain structures when we are still in the womb. However, since sexual differentiation of the genitals takes place in the first two months of pregnancy and sexual differentiation of the brain starts in the second half of pregnancy, these two processes can be influenced independently, which may result in transsexuality. This also means that in the event of ambiguous sex at birth, the degree of masculinization of the genitals may not reflect the degree of masculinization of the brain. There is no proof that social environment after birth has an effect on gender identity or sexual orientation.KEY WORDS: gender identity, homosexuality, human brain, sexual orientation, sexual differentiation, transsexuality. Sexual organization and activation of the human brainThe process of sexual differentiation of the brain brings about permanent changes in brain structures and functions via interactions of the developing neurons with the environment, understood in its widest sense. The environment of a developing neuron is formed by the surrounding nerve cells and the child's circulating hormones, as well as the hormones, nutrients, medication and other chemical substances from the mother and the environment that enter the fetal circulation via the placenta. All these factors may have a lasting effect on the sexual differentiation of the brain. The testicles and ovaries develop in the sixth week of pregnancy. This occurs under the influence of a cascade of genes, starting with the sex-determining gene on the Y chromosome (SRY). The production of testosterone by a boy's testes is necessary for sexual differentiation of the sexual organs between weeks 6 and 12 of pregnancy. The peripheral conversion of testosterone into dihydrotestosterone is essential for the formation of a boy's penis, prostate and scrotum. Instead, the development of the female sexual organs in the womb is based primarily on the absence of androgens (1). Once the differentiation of the sexual organs into male or female is settled, the next thing that is differentiated is the brain, under the influence, mainly, of sex hormones on the developing brain cells. The changes (permanent) brought about in this stage have organizing effects; later, during puberty, the brain circuits that developed in the womb are activated by sex hormones. This paradigm of sexual differentiation of the brain has been well established, ever since the first paper by Phoenix et al. (2). The fetal brain is protected against the effect of circulating estrogens from the mother by the protein α-fetoprotein, which is produced by the fetus and binds strongly to estrogens but not to testosterone (3,4). However, estrogens do not only reach th...

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Section: Sex Differences In the Human Brainsupporting

confidence: 91%

Section: Sex Differences In the Human Brainmentioning

confidence: 45%

Sexual differentiation of the human brain in relation to gender identity and sexual orientation

Savić

Garcı́a-Falgueras

Swaab

2010

Progress in Brain Research

125

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“…In humans, postmortem studies have also discovered several sexually dimorphic nuclei with higher cell numbers and larger volume in males within this region (Allen et al, 1989;Swaab and Fliers, 1985). Clusters of enlarged hypothalamic volume in men as well as in adolescent boys have also been detected in vivo (Goldstein et al, 2001;Lombardo et al, 2012).…”

Section: Discussionmentioning

confidence: 96%

Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain

Hoekzema

Schagen

Kreukels

et al. 2015

Psychoneuroendocrinology

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The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural gray matter (GM) volumes in 55 female-to-male and 38 male-to-female adolescents, 44 boys and 52 girls without GD and applied both univariate and multivariate analyses. In girls, more GM volume was observed in the left superior medial frontal cortex, while boys had more volume in the bilateral superior posterior hemispheres of the cerebellum and the hypothalamus. Regarding the GD groups, at whole-brain level they differed only from individuals sharing their gender identity but not from their natal sex. Accordingly, using multivariate pattern recognition analyses, the GD groups could more accurately be automatically discriminated from individuals sharing their gender identity than those sharing their natal sex based on spatially distributed GM patterns. However, region of interest analyses indicated less GM volume in the right cerebellum and more volume in the medial frontal cortex in female-to-males in comparison to girls without GD, while male-to-females had less volume in * Corresponding author. the bilateral cerebellum and hypothalamus than natal boys. Deviations from the natal sex within sexually dimorphic structures were also observed in the untreated subsamples. Our findings thus indicate that GM distribution and regional volumes in GD adolescents are largely in accordance with their respective natal sex. However, there are subtle deviations from the natal sex in sexually dimorphic structures, which can represent signs of a partial sex-atypical differentiation of the brain.

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“…Homologies between sexually dimorphic nuclei in various animal species including rats, hamsters, guinea pig, gerbils or quail and the dimorphic structures of the preoptic area in humans and monkeys [8,40,[45][46][47]133] remain unclear at present and information coming from different species is still likely to improve our understanding of the neural bases of behavior in primates including humans.…”

Section: Summary and Concluding Statementsmentioning

confidence: 99%

Topography in the preoptic region: Differential regulation of appetitive and consummatory male sexual behaviors

Balthazart

Ball

2007

Frontiers in Neuroendocrinology

193

168

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Several studies have suggested dissociations between neural circuits underlying the expression of appetitive (i.e. sexual motivation) and consummatory components (i.e., copulatory behavior) of vertebrate male sexual behavior. The medial preoptic area (mPOA) clearly controls the expression of male copulation but, according to a number of experiments, is not necessarily implicated in the expression of appetitive sexual behavior. In rats for example, lesions to the mPOA eliminate maletypical copulatory behavior but have more subtle or no obvious effects on measures of sexual motivation. Rats with such lesions still pursue and attempt to mount females. They also acquire and perform learned instrumental responses to gain access to females. However, recent lesions studies and measures of the expression of the immediate early gene c-fos demonstrate that, in quail, subregions of the mPOA, in particular of its sexually dimorphic component the medial preoptic nucleus, can be specifically linked with either the expression of appetitive or consummatory sexual behavior. In particular more rostral regions can be linked to appetitive components while more caudal regions are involved in consummatory behavior. This functional sub-region variation is associated with neurochemical and hodological specializations (i.e. differences in chemical phenotype of the cells or in their connectivity), especially those related to the actions of androgens in relation to the activation of male sexual behavior, that are also present in rodents and other species. It could thus reflect general principles about POA organization and function in the vertebrate brain.

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Two sexually dimorphic cell groups in the human brain

Cited by 428 publications

References 53 publications

Sexual differentiation of the human brain in relation to gender identity and sexual orientation

Sexual differentiation of the human brain in relation to gender identity and sexual orientation

Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain

Topography in the preoptic region: Differential regulation of appetitive and consummatory male sexual behaviors

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