The influence of microsatellite polymorphisms in sex steroid receptor genes ESR1, ESR2 and AR on sex differences in brain structure

Neuroimage. 2020 Nov 1:221:117087. doi: 10.1016/j.neuroimage.2020.117087. Epub 2020 Jun 25.

Abstract

The androgen receptor (AR), oestrogen receptor alpha (ESR1) and oestrogen receptor beta (ESR2) play essential roles in mediating the effect of sex hormones on sex differences in the brain. Using Voxel-based morphometry (VBM) and gene sizing in two independent samples (discovery n ​= ​173, replication ​= ​61), we determine the common and unique influences on brain sex differences in grey (GM) and white matter (WM) volume between repeat lengths (n) of microsatellite polymorphisms AR(CAG)n, ESR1(TA)n and ESR2(CA)n. In the hypothalamus, temporal lobes, anterior cingulate cortex, posterior insula and prefrontal cortex, we find increased GM volume with increasing AR(CAG)n across sexes, decreasing ESR1(TA)n across sexes and decreasing ESR2(CA)n in females. Uniquely, AR(CAG)n was positively associated with dorsolateral prefrontal and orbitofrontal GM volume and the anterior corona radiata, left superior fronto-occipital fasciculus, thalamus and internal capsule WM volume. ESR1(TA)n was negatively associated with the left superior corona radiata, left cingulum and left inferior longitudinal fasciculus WM volume uniquely. ESR2(CA)n was negatively associated with right fusiform and posterior cingulate cortex uniquely. We thus describe the neuroanatomical correlates of three microsatellite polymorphisms of steroid hormone receptors and their relationship to sex differences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cerebral Cortex / anatomy & histology*
  • Cerebral Cortex / diagnostic imaging
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor beta / genetics*
  • Female
  • Gray Matter / anatomy & histology*
  • Gray Matter / diagnostic imaging
  • Humans
  • Hypothalamus / anatomy & histology*
  • Hypothalamus / diagnostic imaging
  • Magnetic Resonance Imaging
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Neuroimaging
  • Polymorphism, Genetic
  • Receptors, Androgen / genetics*
  • Sex Characteristics*
  • White Matter / anatomy & histology*
  • White Matter / diagnostic imaging
  • Young Adult

Substances

  • AR protein, human
  • ESR1 protein, human
  • ESR2 protein, human
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Receptors, Androgen