Molecular basis of Gender Dysphoria: Androgen and estrogen receptors

Spanish scientists confirm the role of androgens and estrogens in brain sexual development

Pink María Fernandez García, a biologist and professor of psychobiology at the University of A Coruña, is one of the researchers of Research Group in Behavioral and Molecular Diagnostics Applied to Health (DICOMOSAHer research interests focus primarily on the molecular basis of learning, the negative effects of child abuse, and the development of brain feminization/masculinization. On this last topic, she has several publications of high scientific quality on the molecular and endocrine basis of transsexuality. On a personal note, we recognize her as a woman who combines the reflective detachment characteristic of science with the emotional depth of a devoted adoptive mother to three African children. You can consult her personal blog here.

But here I do not intend to construct a personal profile of Dr. Rosa María; what I present as news are the results of her latest publication in the international journal Psychoneuroendochronology. ¹ We previously reviewed their article on the same topic, which you can find here:

According to the authors of the research, although transsexuality has been linked to sex steroid receptors, the results have been inconsistent until now. They argue that this inconsistency could be due to excessively small sample sizes and the heterogeneity among the subjects diagnosed with gender dysphoria included in the studies—negative aspects that they attempt to address in the work under discussion.

The publication I am referring to investigates the role played by the androgen receptor (AR), estrogen receptors alpha (ERalpha) and beta (ERbeta), and the aromatase enzyme (CYP19A1) in a large, homogeneous sample of transsexuals, both MtF ² (n= 549), as FtM ³ (n= 425).

The results The following findings highlight the following:

1. In the development of atypical MtF gender identity there is an inverse interaction between the ERbeta and AR polymorphisms.
2. However, in the development of the atypical FtM gender identity, although the ERbeta and/or ERalfa polymorphisms are involved, there is no interaction between them, as is the case in the MtF gender identity.
3. Furthermore, the ERbeta and alpha polymorphisms are also involved in the development of typical male and female gender identity.
4. There is a common characteristic in MtF and FtM gender identities: the involvement of the same polymorphisms in both estrogen receptors.

The action of estrogens in masculinization, feminization and brain sexual behavior is widely demonstrated, as well as their role in brain growth and differentiation.

The authors conclude This highlights that the key receptors in the brain feminization/masculinization process can follow two pathways: in cases of male-to-female (MtF) transsexuality, a specific allele combination of ERbeta, ERalfa, and AR would occur. Similarly, female-to-male (FtM) transsexuality is associated with specific polymorphisms of the ERbeta and ERalfa receptors, but not AR.

1. Rosa Fernández, Antonio Guillamón et al. Molecular basis of Gender Dysphoria: androgen and estrigen receptor interaction. Psychoneuroendocrinology, 2018, 98, 161-167
2. Male to female transsexuality
3. Female to male transsexuality