Perimenopausal regulation of steroidogenesis in the nonhuman primate

Krystina G. Sorwell, Steven Kohama, Henryk Urbanski

    Research output: Contribution to journalArticle

    22 Citations (Scopus)

    Abstract

    Human aging is characterized by a marked decrease in circulating levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), hormonal changes associated with cognitive decline. Despite beneficial effects of DHEA supplementation in rodents, studies in elderly humans have generally failed to show cognitive improvement after treatment. In the present study we evaluate the effects of age and estradiol supplementation on expression of genes involved in the de novo synthesis of DHEA and its conversion to estradiol in the rhesus macaque hippocampus. Using reverse transcription polymerase chain reaction (RT-PCR) we demonstrate the expression of genes associated with this synthesis in several areas of the rhesus brain. Furthermore, real-time PCR reveals an age-related attenuation of hippocampal expression level of the genes CYP17A1, STS, and 3BHSD1/2. Additionally, short-term administration of estradiol is associated with decreased expression of CYP17A1, STS, SULT2B1, and AROMATASE, consistent with a downregulation not only of estrogen synthesis from circulating DHEA, but also of de novo DHEA synthesis within the hippocampus. These findings suggest a decline in neurosteroidogenesis may account for the inefficacy of DHEA supplementation in elderly humans, and that central steroidogenesis may be a function of circulating hormones and menopausal status.

    Original languageEnglish (US)
    JournalNeurobiology of Aging
    Volume33
    Issue number7
    DOIs
    StatePublished - Jul 2012

    Fingerprint

    Dehydroepiandrosterone
    Primates
    Estradiol
    Gene Expression
    Hippocampus
    Dehydroepiandrosterone Sulfate
    Macaca mulatta
    Reverse Transcription
    Real-Time Polymerase Chain Reaction
    Rodentia
    Estrogens
    Down-Regulation
    Hormones
    Polymerase Chain Reaction
    Brain

    Keywords

    • Aging
    • Dehydroepiandrosterone
    • Hormone replacement
    • Menopause
    • Neurosteroidogenesis

    ASJC Scopus subject areas

    • Clinical Neurology
    • Neuroscience(all)
    • Aging
    • Developmental Biology
    • Geriatrics and Gerontology

    Cite this

    Perimenopausal regulation of steroidogenesis in the nonhuman primate. / Sorwell, Krystina G.; Kohama, Steven; Urbanski, Henryk.

    In: Neurobiology of Aging, Vol. 33, No. 7, 07.2012.

    Research output: Contribution to journalArticle

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