We are investigating the relationship of estradiol (and other estrogens) esterification to the protection of LDL from oxidation. We are studying the ability of the various E2-esters to protect LDL from oxidation in several model systems, including oxidation by several different cells. Further, we are investigating various pharmacological estrogens for their ability to be esterified by LCAT. Some of these commonly used estrogens are not esterified at all, while others are esterified at rates more rapid than E2. Obviously, if our hypothesis linking LCAT esterification to protection against atherosclerosis is correct, these differences can have important ramifications in women's health. Other studies are investigating whether E2, in contrast to potent estrogens that we have found, are not esterified can protect against atherosclerosis in vivo. For this study we are using the LDL-receptor knockout mouse, an animal that has high levels of LDL, and develops heart disease rapidly. Other studies are investigating the mechanism by which tiny amounts of the E2-esters interferes with LDL oxidation.
Estradiol-esters in the ovary
In addition to these studies, we are investigating the role of the estradiol esters in cell growth and proliferation in the ovary. It is known that oxidative stimulation by small amounts of various oxidants cause cell proliferation. We have found that ovarian follicular fluid contains very large amounts of LCAT synthesized E2-esters. The hypothesis that we are investigating is these estrogen esters control the growth of ovarian thecal cells.
We have shown that relatively large amounts of testosterone fatty acid esters are present in male fat. These esters are highly androgenic and have a very long biological half-life because they are protected from metabolic catabolism. We hypothesize that these esters are capable of paracrine stimulation of the growth of neighboring androgen target organs and thus, because of their proximity, can maintain these organs without a requirement for blood-borne testosterone. We are investigating the effect of various trophic factors and hormones on the synthesis and hydrolysis of androgen esters, and the correlation of these stimuli in the growth or maintenance of various androgen dependent organs.