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Steroid hormones and brain development: some guidelines for understanding actions of pseudohormones and other toxic
1Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021.
Abstract:
Gonadal, adrenal, and thyroid hormones affect the brain directly, and the sensitivity to hormones begins in embryonic life with the appearance of hormone receptor sites in discrete populations of neurons. Because the secretion of hormones is also under control by its neural and pituitary targets, the brain-endocrine axis during development is in a delicately balanced state that can be upset in various ways, and any agent that disrupts normal hormone secretion can upset normal brain development. Moreover, exogenous substances that mimic the actions of natural hormones can also play havoc with CNS development and differentiation. This paper addresses these issues in the following order: First, actions of glucocorticoids on the developing nervous system related to cell division dendritic growth and neurotransmitter phenotype will be presented followed by a discussion of the developmental effects of synthetic steroids. Second, actions of estrogens related to brain sexual differentiation will be described, followed by a discussion of the actions of the nonsteroidal estrogen, diethylstilbestrol, as an example of exogenous estrogenic substances. The most important aspect of the potency of exogenous estrogens appears to be the degree to which they either bypass protective mechanisms or are subject to transformations to more active metabolites. Third, agents that influence hormone levels or otherwise modify the neuroendocrine system, such as nicotine, barbiturates, alcohol, opiates, and tetrahydrocannabinol, will be noted briefly to demonstrate the diversity of toxic agents that can influence neural development and affect personality, cognitive ability, and other aspects of behavior.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Hormones and external substances significantly impact developing brain function, affecting neural pathways and behavior. Disruptions during embryonic development can lead to lasting changes in personality and cognitive abilities.
Area of Science:
- Neuroendocrinology
- Developmental Neuroscience
Background:
- Hormones like gonadal, adrenal, and thyroid hormones directly influence brain development from embryonic stages.
- The brain-endocrine axis is a delicate system susceptible to disruption by various agents.
- Exogenous substances mimicking natural hormones can severely impact central nervous system (CNS) development.
Purpose of the Study:
- To examine the effects of hormones and exogenous substances on the developing nervous system.
- To discuss the impact on cell division, dendritic growth, neurotransmitter phenotype, and brain sexual differentiation.
- To highlight how neuroendocrine system modifications influence behavior and cognitive abilities.
Main Methods:
- Review of existing literature on hormonal and exogenous substance effects on neural development.
- Analysis of glucocorticoid and estrogen actions on the developing brain.
- Discussion of the impact of synthetic steroids and nonsteroidal estrogens like diethylstilbestrol.
- Brief overview of agents like nicotine, alcohol, and opiates affecting the neuroendocrine system.
Main Results:
- Glucocorticoids influence cell division, dendritic growth, and neurotransmitter phenotypes in the developing nervous system.
- Estrogens play a critical role in brain sexual differentiation, with exogenous estrogens like DES posing significant risks.
- Synthetic steroids and various exogenous agents can disrupt normal brain development and differentiation.
Conclusions:
- The developing brain is highly sensitive to hormonal and exogenous influences.
- Disruptions to the brain-endocrine axis during development can have profound and lasting effects on behavior and cognition.
- Understanding these impacts is crucial for preventing developmental abnormalities.