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

Abstract

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...

The Change of Heterosexual Preference in Adolescents: Implications of Stress and Cognitive Regulation on Sexual Orientation

“…Some researchers focused on the organizing effect of prenatal sex steroid hormones and the key role of hypothalamus. They insisted that sexual orientation is determined during early development, as well as the physiological gender, and left little room for learning models of sexual orientation Rahman, 2005;Savic, Garcia-Falgueras, & Swaab, 2010;Swaab, 2004). However, their hypothesis is not compatible with the clinical data and genetic research findings (Davis et al, 1996;Friedman & Downey, 2010;Joel, 2011;Langstrom, Rahman, Carlstrom, & Lichtenstein, 2010), and our case presentation.…”

“…Many researchers pointed to the third interstitial nucleus of the anterior hypothalamus, because it is 2.5 times larger in men than in women, and this volume difference in other mammals results from prenatal testosterone exposure (Herbert, 2008;Savic, Garcia-Falgueras, & Swaab, 2010). Moreover, patterns of cerebral asymmetry and functional brain connectivity/network are also linked to sexual orientation in men and women (Savic & Lindstrom, 2008;Corsello et al, 2011).…”

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

“…Leading theories on the etiology of this condition involve a sex-atypical cerebral programming that diverges from the sexual differentiation of the rest of the body, postulated to reflect the organizational effects of altered levels of sex steroid hormones during a specific period of fetal development (Bao and Swaab, 2011;CohenKettenis and Gooren, 1999;Savic et al, 2010;Swaab, 2007). Some twin studies suggest a role for genetic factors in the development of GD, potentially involving polymorphisms in genes encoding elements of the sex steroid signaling or metabolic pathways (Heylens et al, 2012).…”

Sex differences in the brain–an interplay of sex steroid hormones and sex chromosomes

“…SDN is believed to be involved in the regulation of male sexual behaviour [74] although its precise role has not yet been determined. Interestingly, some studies also suggested SDN's role in a partner preference in rams [75] and even in humans [76], although differences in SDN volume between homosexual and heterosexual men were not confirmed by follow-up studies, and it is now accepted that SDN does not have a role in sexual orientation in humans (reviewed in [77]). …”