Understanding the broad influence of sex hormones and sex differences in the brain

Abstract

Sex hormones act throughout the entire brain of both males and females via both genomic and non-genomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes where they are associated with presynaptic terminals, mitochondria, spine apparatus, post-synaptic densities. Sex hormone receptors also are found in glial cells. Hormonal regulation of a variety of signaling pathways as well as direct and indirect effects upon gene expression induce spine synapses, up- or down-regulate and alter the distribution of neurotransmitter receptors, regulate neuropeptide expression and cholinergic and GABAergic activity as well as calcium sequestration and oxidative stress. Many neural and behavioral functions are affected, including mood, cognitive function, blood pressure regulation, motor coordination, pain and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not-yet-precisely-defined genetic factors including the mitochondrial genome. These sex differences and responses to sex hormones in brain regions, and upon functions not previously regarded as subject to such differences, indicates that we are entering a new era of our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

Effects of social subordination and oestradiol on resting‐state amygdala functional connectivity in adult female rhesus monkeys

“…Previous studies have demonstrated that both people suffering from depression and male rats subjected to chronic stress have exhibited hippocampal atrophy . By contrast, female rats showed neuroprotective actions from E2 in the hippocampus, which appeared to spare them from the damage observed in male rats following chronic stress by regulating tropic factors and excitatory neurotransmission to maintain hippocampal activity within an optimal range . Hence, our results suggest that in DOM females E2 treatment improved hippocampal function and enhanced FC with the amygdala, whereas, in SUB females, E2 worked towards the same end, albeit by reducing FC.…”

Ovarian hormones: a long overlooked but critical contributor to cognitive brain structures and function

“…When studying ovarian hormones, it is important to consider the nature of effects. Broadly, sex hormone effects on the brain and behavior can be organizational or activational . Organizational effects generally concern hormone exposure during sensitive periods of development; they are permanent and have historically been tied to sexual differentiation, in that hormone‐influenced brain circuits persist throughout life and are important for sex‐typed behaviors.…”

Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders

“…It is now well established that organizational and activational effects of sex steroid hormones play an important role in brain sex differentiation [7,28,29,30,31]. Indeed, neuroprotective actions of estrogen in females underlie sex differences in susceptibility to disorders such as PD and schizophrenia [7,32,33,34], whilst aberrant levels of fetal testosterone have been associated with male preponderance to neurodevelopmental disorders such as autism and ADHD [35,36].…”