Causes and consequences of age-related steroid hormone changes: Insights gained from nonhuman primates

K. G. Sorwell, H. F. Urbanski

    Research output: Contribution to journalReview article

    16 Scopus citations

    Abstract

    Similar to humans, rhesus macaques (Macaca mulatta) are large, long-lived diurnal primates, and show similar age-related changes in the secretion of many steroid hormones, including oestradiol, testosterone, cortisol and dehydroepiandrosterone (DHEA). Consequently, they represent a pragmatic animal model in which to examine the mechanisms by which these steroidal changes contribute to perturbed sleep-wake cycles and cognitive decline in the elderly. Using remote serial blood sampling, we have found the circulating levels of DHEA sulphate, as well as oestradiol and testosterone, decline markedly in old monkeys. Furthermore, using the real-time polymerase chain reaction, we have shown that the genes for the enzymes associated with the conversion of DHEA to oestradiol and testosterone (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and aromatase) are highly expressed in brain areas associated with cognition and behaviour, including the hippocampus, prefrontal cortex and amygdala. Taken together, these findings suggest that the administration of supplementary DHEA in the elderly may have therapeutic potential for cognitive and behavioural disorders, although with fewer negative side effects outside of the central nervous system. To test this, we have developed a novel steroid supplementation paradigm for use in old animals; this involves the oral administration of DHEA and testosterone at physiologically relevant times of the day to mimic the circadian hormone patterns observed in young adults. We are currently evaluating the efficacy of this steroid supplementation paradigm with respect to reversing age-associated disorders, including perturbed sleep-wake cycles and cognitive decline, as well as an impaired immune response.

    Original languageEnglish (US)
    Pages (from-to)1062-1069
    Number of pages8
    JournalJournal of Neuroendocrinology
    Volume25
    Issue number11
    DOIs
    StatePublished - Nov 1 2013

    Keywords

    • Circadian rhythms
    • Dehydroepiandrosterone
    • Oestradiol
    • Testosterone

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology
    • Endocrine and Autonomic Systems
    • Cellular and Molecular Neuroscience

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