Neurosteroids’ effects and mechanisms for social, cognitive, emotional, and physical functions

Abstract

SummaryHormones are trophic factors that integrate central and peripheral nervous system functions, and can influence social, cognitive, emotional and physical (SCEP) processes. Greater understanding of behavioral and neurobiological underpinnings of mental, cognitive, and/or physical changes with maturation is becoming increasingly important as the world's population ages. There are individual differences in how people age, but the factors that influence these differences are not well understood. Social supports are one factor that may influence the trajectory of age-related processes. The loss of close relationships, especially among older persons, is one of the greatest risk factors for mental and physical decline. Progesterone, secreted by the ovaries, or produced de novo in the brain, is readily converted centrally to 5α-pregnan-3α-ol-20-one (3α,5α-THP), and can influence SCEP, through rapid, non-classical steroid-mediated actions. Our hypothesis is that 3α,5α-THP is a key trophic factor in SCEP and development. Our research has demonstrated that 3α,5α-THP facilitates social and sexual behavior of rodents, which evokes further increases in 3α,5α-THP in midbrain and hippocampus, brain areas involved in SCEP. The role of 3α,5α-THP to influence social and/or sexual experience, and thereby SCEP, is discussed in this review. Further understanding of these neurobiological and/or behavioral factors may lead to findings that ultimately can promote health and prevent disease.

Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine–serotonin systems in the prefrontal cortex of juvenile female rats

“…Besides dihydrotestosterone (DHT) synthesis, 5α-R is the rate-limiting enzyme in the biosynthesis of 3α,5α-reduced neurosteroids (3α,5α-NS), such as allopregnanolone (AlloP). 3α,5α-NS modulate emotional responses and cognitive function (Frye, 2009;Paris et al, 2011b), which are mediated in part by the PFC (Davidson, 2002;Paris et al, 2011b). With this in mind and the finding that short-term exposure to BPA affects 5α-R levels in the PFC of adult female rats (Castro et al, 2013b), we believe that this enzyme might be a potential target for BPA-mediated effects in the female perinatal brain.…”

Environmental enrichment attenuates the age-related decline in the mRNA expression of steroidogenic enzymes and reduces the methylation state of the steroid 5α-reductase type 1 gene in the rat hippocampus

“…Young rats, which have higher allopregnanolone levels in the cortex (proestrous and late pregnancy), have been shown to exhibit better performance on the object recognition task than diestrous rats or rats in early pregnancy (Frye, 2009). Similarly, other studies have indicated that allopregnanolone can improve memory impairment and inhibit the symptoms of aging and neurodegenerative diseases.…”

Sex differences in the physiology of eating

“…Recognition of its importance has fundamentally changed endocrinology in recent decades. In the brain, locally produced steroids are called neurosteroids (240,477,478,611). In anthropoid primates, the adrenal glands are a major source of precursor molecules for local steroid synthesis.…”