Steroid Hormone Biochemistry Research

Richard Hochberg, Ph.D.

Our laboratory is involved in a broad array of studies concerning the actions of members of the various families of steroid hormones, including glucocorticoids, and more specifically the sex steroids, especially estrogens and androgens. Our interests are concentrated in two areas: The first includes the investigation of the actions of a unique metabolite of steroids that were first discovered in our laboratory, the steroid fatty acid esters. While we have shown these non-polar metabolites exist in all of the steroids families, our current studies are concentrated on androgen and estrogen esters. These esters are the most potent of the naturally occurring sex steroids. Furthermore, the estrogen fatty acid esters have been shown to be intimately involved in inhibiting the biological factors known to initiate atherosclerosis; and it is suspected that their absence may be a crucial factor in the increase in heart disease that accompanies the menopause. We are performing various studies on the relationship of the estrogen fatty acid esters to processes involved in heart disease.

The second area of interest in this laboratory concerns the use of synthetic chemisty to design and produce unusual steroid receptor ligands that are biological probes with important research, diagnostic and therapeutic uses. For example, we are conducting experiments to design an estrogen that is capable of acting only locally and not systemically. This estrogen would be useful for the treatment of vaginal dyspareunia, and aging skin in women for whom systemic estrogen therapy is contraindicated, or who are not willing to take the risks associated with estrogen treatment. In addition to these studies, our laboratory is designing and synthesizing radiochemical probes for diagnostic purposes. These biologically active steroids have properties that allow visualizing tissues and tumors through steroid receptor mediated action. These radiochemical probes include 123I estrogens for SPECT imaging of breast cancer, 18F-androgens for PET imaging of prostate and ovarian cancer; 18F-glucocorticoids for PET imaging of the brain. Using these radiolabelled hormones, cancers can be localized and the effects of surgery and chemotherapy can be assessed.