Sex Hormones
sex hormones
Sex hormone regulation of neural gene expression
Gonadal steroid hormones are the principal drivers of sex-variable biology in vertebrates. In the brain, estrogen (17β-estradiol) establishes neural sex differences in many species and modulates mood, behavior, and energy balance in adulthood. To understand the diverse effects of estradiol on the brain, we profiled the genomic binding of estrogen receptor alpha (ERα), providing the first picture of the neural actions of any gonadal hormone receptor. To relate ERα target genes to brain sex differences we assessed gene expression and chromatin accessibility in the posterior bed nucleus of the stria terminalis (BNSTp), a sexually dimorphic node in limbic circuitry that underlies sex-differential social behaviors such as aggression and parenting. In adult animals we observe that levels of ERα are predictive of the extent of sex-variable gene expression, and that these sex differences are a dynamic readout of acute hormonal state. In neonates we find that transient ERα recruitment at birth leads to persistent chromatin opening and male-biased gene expression, demonstrating a true epigenetic mechanism for brain sexual differentiation. Collectively, our findings demonstrate that sex differences in gene expression in the brain are a readout of state-dependent hormone receptor actions, rather than other factors such as sex chromosomes. We anticipate that the ERα targets we have found will contribute to established sex differences in the incidence and etiology of neurological and psychiatric disorders.
Dynamic endocrine modulation of the nervous system
Sex hormones are powerful neuromodulators of learning and memory. In rodents and nonhuman primates estrogen and progesterone influence the central nervous system across a range of spatiotemporal scales. Yet, their influence on the structural and functional architecture of the human brain is largely unknown. Here, I highlight findings from a series of dense-sampling neuroimaging studies from my laboratory designed to probe the dynamic interplay between the nervous and endocrine systems. Individuals underwent brain imaging and venipuncture every 12-24 hours for 30 consecutive days. These procedures were carried out under freely cycling conditions and again under a pharmacological regimen that chronically suppresses sex hormone production. First, resting state fMRI evidence suggests that transient increases in estrogen drive robust increases in functional connectivity across the brain. Time-lagged methods from dynamical systems analysis further reveals that these transient changes in estrogen enhance within-network integration (i.e. global efficiency) in several large-scale brain networks, particularly Default Mode and Dorsal Attention Networks. Next, using high-resolution hippocampal subfield imaging, we found that intrinsic hormone fluctuations and exogenous hormone manipulations can rapidly and dynamically shape medial temporal lobe morphology. Together, these findings suggest that neuroendocrine factors influence the brain over short and protracted timescales.
Exploring sex hormones and menstrual cycle influence on fear memory through a multidimensional approach
FENS Forum 2024
Sex hormones-dependent modulation of thalamic inputs to striatal fast-spiking interneurons
FENS Forum 2024