DHEA effects on brain and behavior: Insights from comparative studies of aggression

Gene Devine

Super Moderator
DHEA serum production, like testosterone, decrease as we age. Life Extension for many years has advocated daily supplementation to make up for this deficiency. More importantly to men on TRT where upstream metabolites are compromised due to HTPA suppression supplementing to "back fill" the pathways is just as important. In the abstract below there are some very important take aways for supplementing DHEA.

Highlights• We review the essential roles of DHEA in the regulation of aggression, an important social behavior.
• We integrate studies of songbirds, rodents, non-human primates, and humans.
• Songbirds and hamsters are excellent small animal models for studying the functions of DHEA.
• The brain is an important target of DHEA.


Abstract
Historically, research on the neuroendocrinology of aggression has been dominated by the paradigm that the brain receives sex steroid hormones, such as testosterone (T), from the gonads, and then these gonadal hormones modulate behaviorally relevant neural circuits. While this paradigm has been extremely useful for advancing the field, recent studies reveal important alternatives. For example, most vertebrate species are seasonal breeders, and many species show aggression outside of the breeding season, when the gonads are regressed and circulating levels of gonadal steroids are relatively low. Studies in diverse avian and mammalian species suggest that adrenal dehydroepiandrosterone (DHEA), an androgen precursor and prohormone, is important for the expression of aggression when gonadal T synthesis is low. Circulating DHEA can be converted into active sex steroids within the brain. In addition, the brain can synthesize sex steroids de novo from cholesterol, thereby uncoupling brain steroid levels from circulating steroid levels. These alternative mechanisms to provide sex steroids to specific neural circuits may have evolved to avoid the costs of high circulating T levels during the non-breeding season. Physiological indicators of season (e.g., melatonin) may allow animals to switch from one neuroendocrine mechanism to another across the year. DHEA and neurosteroids are likely to be important for the control of multiple behaviors in many species, including humans. These studies yield fundamental insights into the regulation of DHEA secretion, the mechanisms by which DHEA affects behavior, and the brain regions and neural processes that are modulated by DHEA. It is clear that the brain is an important site of DHEA synthesis and action.
 

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Understanding Your Hormones

Estradiol (E2)

A form of estrogen produced from testosterone. Important for bone health, mood, and libido. Too high can cause side effects; too low can affect well-being.

DHT

Dihydrotestosterone is a potent androgen derived from testosterone. Affects hair growth, prostate health, and masculinization effects.

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The biologically active form of testosterone not bound to proteins. Directly available for cellular uptake and biological effects.

Scientific Reference

Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab. 2010 Aug;95(8):3955-64.

DOI: 10.1210/jc.2010-0102 | PMID: 20534765 | PMCID: PMC2913038

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