PET imaging of brain sex steroid hormone receptors and the role of estrogen in depression

Androgens and estrogens are steroid hormones that are involved in several neurodegenerative and psychiatric disorders. Decreased levels of steroid hormones are associated with e.g. decreased cognition, anxiety and depression. Androgens and estrogens exert their biological effects through their corresponding receptors. To better understand the role of androgen and estrogen receptors in the brain, it would be advantageous to be able to quantify the expression of these receptors in living subjects.

Positron emission tomography (PET) is a non-invasive imaging technique that may allow quantification of steroid receptors in the brain. FDHT and FES are validated PET tracers for imaging of androgen and estrogen receptors in respectively prostate and breast cancer. In this thesis, FDHT and FES were evaluated as PET tracers for imaging of androgen and estrogen receptors in the brain of male and female rats. However, FDHT PET proved unsuitable for imaging of brain androgen receptors, whereas FES PET was only able to visualize estrogen receptors in brain regions with high receptor density like pituitary and hypothalamus.

Furthermore, the effect of estrogen replacement and stress on brain activity (FDG PET) and behavior (forced swim test, open-field test) was evaluated in ovariectomized rats with reduced levels of circulating estrogens. Ovariectomized rats are considered as a model for post-menopausal women. Immediate treatment with estrogens could prevent a reduction in metabolism in fear processing brain regions and the depression-like behaviors induced by ovariectomy. Exposure to additional stress did not aggravate the effect of estrogen depletion on depressive-like behavior and brain metabolism.

Dissertation: http://hdl.handle.net/11370/c5578a14-a23b-4b0d-a5ed-10c71b315313