Abstract
Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo.
Highlights
Over the last decades, several lines of research have extended the pivotal actions of ovarian hormones such as estrogen and progesterone outside of the reproductive tract
Further work in animal models mimicking the hormonal environment of the postpartum period revealed a characteristic behavioral phenotype with vulnerability to helplessness, increased anxiety, and aggression that has been associated with differences in expression of several key genes, such as 5-HTT, brain-derived neurotrophic factor (BDNF), glutamatergic and γ-aminobutyric acid (GABA)-A receptor type 4 (Suda et al, 2008)
Pharmacological and behavioral approaches have been combined to demonstrate the critical role of sex steroid hormones in mediating effects on synaptic plasticity, memory, mood, and cognition
Summary
Several lines of research have extended the pivotal actions of ovarian hormones such as estrogen and progesterone outside of the reproductive tract. Several mechanisms through which ovarian hormones may influence glutamatergic neurotransmission have been proposed: progesterone has been shown to suppress the excitatory glutamate response in a dosedependent fashion (Smith et al, 1987a), while estrogen exhibits facilitating effects on glutamate transmission (Yokomaku et al, 2003).
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