The role of androgens in the female has been thought to be merely as a precursor steroid to the production of estrogens. However, a previous publication by Dr. Wes Garrett, a former graduate student in this laboratory, reported on the discovery of a novel steroidogenic pathway which converts androstenedione to the very potent anabolic androgen, 19-nortestosterone. Currently, we have localized high amounts of nuclear androgen receptors immunohistochemically to the granulosa cells and demonstrated that androgens, not estrogens, synergize with FSH in vitro to induce aromatase enzyme and LH receptors. Future studies will be aimed towards not only defining the mechanism by which androgens and gonadotropins interact to induce these and other parameters, but to also identify specific proteins induced by androgens and possible mediation of growth factors to elicit the androgen response.

 

The second area of research is a collaborative effort with Dr. Ellen Silbergeld (Department of Epidemiology and Toxicology). Our past efforts have been directed at the effect of paternal lead exposure on embryo development and their subsequent generations. These studies have demonstrated that low levels of paternal lead exposure upregulates a specific protein which appears at the two-cell stage and also results in seriously impairing hippocampal neuronal development with reduced offspring. The reduced numbers of siblings appears to be consequence of a decrease in number of embryos which implant within the uterus, and not the number of embryos fertilized. Our future studies will be concerned with identifying this major protein induced at the two cell stage, since this is the time period that paternal genes are expressed in rodent embryo, and other studies will be directed at lead alteration of zinc-finger loop proteins (protamines, protein kinases, etc.) and paternally imprinted genes, e.g., IGF II.