In mammals, sex differences in the adult brain are established very early in development, when the brain is still very immature. In the case of having inherited the SRY gene, during embryogenesis, testosterone secreted by the testes enters the brain and is converted to estradiol by the aromatase. Then the estradiol acts by binding to intracellular estrogen receptors (ERs) located predominantly in neurons, masculinizing specific brain regions. But ERs are also transcription factors that, when they are exposed to their ligand, dimerize and form complexes with coactivator proteins and corepressors, modifying the transcription of multiple target genes in a cascade effect and ultimately neuronal function. Given the intimate relationship between steroids and brain dimorphism, and steroid coactivators and gene transcription, in the present work, we further explore the implication of ERs α and β, and steroid coactivators NCoA-1, NCoA-2, NCoA-3, NCoA-4, NCoA-5 and p300-CREBBP, in the genesis of brain dimorphism. Based on our data, we believe that the coactivators NCOA-1, NCOA-2 and p300-CREBBP could be considered as candidate genes for GI.
Part of the book: Oxytocin and Health
Gender incongruence (GI) is defined as an individual’s discontent with their assigned gender at birth and their identification with a gender other than that associated with their sex based on physical sex characteristics. The origin of GI appears to be multifactorial. From the extensive research that has been conducted over the past few years, four main factors have been identified as key mechanisms: genes, hormones, epigenetics, and the environment. One of the current hypotheses suggests that GI could be related to a different sexual differentiation of the brain as a result of changes in the DNA sequence of the estrogen receptors ERs and androgen receptor AR genes. These changes in the DNA sequence would imply a variability in the sensitivity of the hormone receptors, causing a genetic vulnerability.
Part of the book: Human Sexuality