Endocrine Abstracts (2007) 13 P272

A central physiological role for attenuated circulating DHEAS levels in aged female Rhesus Macaques?

Henryk Urbanski, Dario Lemos, Brandon Sitzmann, Vasilios Garyfallou & Steven Kohama

In humans and rhesus monkeys (Macaca mulatta) the zona reticularis of the adrenal gland produces large amounts of dehydoepiandrosterone (DHEA) and its sulfated form, DHEAS. The circulating levels of these steroids are particularly high during early adulthood, and they then decline gradually during aging, especially in females. To help elucidate the physiological function of this steroidal loss we examined the 24-hour plasma profiles of DHEAS in female rhesus monkeys, using a remote blood sampling set-up that comprised an iv catheter and swivel. RIA of the plasma samples revealed a pronounced 24-hour rhythm of DHEAS, with peaks occurring in the morning in association with activity onset, and nadirs in the evening in association with sleep onset. Importantly, plasma DHEAS levels showed a marked age-associated attenuation, which preceded the onset of menopause.

Because DHEA and DHEAS are known precursors in the biosynthesis of sex steroids, we also examined whether specific brain areas express the enzymes necessary for the complete conversion of DHEA and DHEAS to estradiol. Using RT-PCR we detected the expression of the following key genes in the amygdala, hippocampus, hypothalamus and prefrontal cortex: sulfatase, sulfotransferase, 17β-HSD-4, 3β-HSD-2, and aromatase. Taken together, the data suggest that postmenopausal changes in estrogen-dependent brain functions may stem not only from a decreased output of ovarian estradiol but also from a decreased output of adrenal DHEA and DHEAS.

Supported by NIH Grants AG19914, HD29186 and RR00163.

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