TY - JOUR
T1 - Perimenopausal regulation of steroidogenesis in the nonhuman primate
AU - Sorwell, Krystina G.
AU - Kohama, Steven G.
AU - Urbanski, Henryk F.
N1 - Funding Information:
We thank Vasilios Garyfallou for help with blood sample processing and with the design of gene primers and probes. This work was supported by NIH grants AG023477 , AG029612 , AG036670 , HD018185 , HD029186 , and RR000163 .
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
KW - Aging
KW - Dehydroepiandrosterone
KW - Hormone replacement
KW - Menopause
KW - Neurosteroidogenesis
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U2 - 10.1016/j.neurobiolaging.2011.05.004
DO - 10.1016/j.neurobiolaging.2011.05.004
M3 - Article
C2 - 21683476
AN - SCOPUS:84861200815
SN - 0197-4580
VL - 33
SP - 1487.e1-1487.e13
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 7
ER -