Larry D. Anderson, Ph.D.
Laboratory of Ovarian Endocrinology
A major focus within this laboratory has been on the metabolism of androgens in the ovary, since an imbalance of this steroidogenic pathway is associated with various reproductive disorders, e.g. hirsutism, polycystic ovarian disease, and postmenopause. Those studies revealed the ovarian production of large amounts of a previously unreported steroid, 19-oic-androstenedione identified by HPLC and GC/MS, which serves as precursor of the highly potent androgen, 19-nor-testosterone by granulosa cells, in vitro. We have demonstrated specific androgen receptors in the nuclei of granulosa and stromal cells by immunohistochemistry, and a synergistic action with FSH to induce aromatase enzyme activity and LH receptors. Present studies center on quantifying the number of androgen receptors and mRNA expression during follicular development using Scatchard analysis and RNA protection assays, respectively. Subsequent investigations will concentrate on the specific gene products regulated by androgens throughout the development of the follicle and ovarian stromal cells. Other studies concentrate on the effects of lead (Pb++) on male reproduction. While lead is toxic to mammalian reproduction and development, its effects on prenatal development are assumed to be primarily related to in utero exposures via exposed mothers. Our recent studies provide evidence that lead affects the initial genomic expression in embryos fathered by males exposed to lead at concentrations well below that which affect their fertility. This effect is first observed as a dose- dependent increase in a predominant set of at least 5 proteins appearing at first cleavage with approximate molecular weights of 68-70 kD. A similar set of proteins are also observed in mouse embryos and implicated as the initial expression of the embryonic genome involving paternal genes. Studies are continuing to identify by 2-D gels and Western blotting this set of proteins, in addition to possible modification of sperm protamines, protein kinase C, and other proteins containing zinc finger loops, as well as determine a transgenerational effect by examining F2 embryos resulting from F1 animals not directly exposed to lead.
Recent Publications
Garrett WM, Hoover DJ, Shackleton CHL, Anderson LD 1991 Androgen metabolism by porcine granulosa cells during the process of luteinization in vitro: Identification of 19-oic-androstenedione as a major metabolite and possible precursor for the formation of C18 neutral steroid. Endocrinology 129:2941-1950.
Garrett WM, Anderson LD 1994 Androgen modulation of FSH action in porcine granulosa cells and immunohistochemical localization of androgen and estrogen receptors in porcine ovaries. Society for the Study of Reproduction 50:151.
Gandley RE, Couture M, Silbergeld EK, Anderson LD 1992 Paternal exposure to lead alters initial genomic expression in offspring. Society of Toxicology 12:213.
Gandley RE, Anderson LD, Silbergeld ED 1995 Lead: Male-mediated effects on reproduction and development in the rat. Proceedings of the National Academy of Science USA, in press.
