Histology, Cell biology
Estrogens regulate a variety of cellular and developmental responses, through interaction of the hormone with specific receptors of the nuclear receptor superfamily. After binding an estrogen, the receptor-estrogen complex mediates changes in transcription in the nucleus of the cell that lead to specific hormonal responses. Dr. Welshons’ lab studies the mechanisms by which estrogens regulate the synthesis and degradation of the estrogen receptor protein and message in estrogen-responsive MCF-7 human breast cancer cells, mechanisms of estrogen-stimulated proliferation, and the progression of breast cancer cells from hormone dependence to hormone independence. In addition, his lab studies estrogen action in fetal development, its relationship to environmental xenoestrogen exposure, and the mechanisms and prediction of environmental endocrine disruptor effects on the development of the reproductive tract. One current focus in this is how the physiology of delivery of environmental estrogens can substantially increase the impact of selected environmental estrogens on fetal development, relative to weak activity in the adult. This work on circulating xenobiotic estrogens studied in tissue culture models, tested in animal models in collaboration with F.S. vom Saal also at this institution, contributes to the national regulatory process for the evaluation of endocrine disruption by synthetic chemicals.
Nagel, S.C., vom Saal, F.S., Thayer, K.A., Dahr, M.G., Boechler, M. and Welshons, W.V., 1997. Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vitro bioactivity of the xenobiotic estrogens bisphenol A and 4-octylphenol. Environ. Health Perspect. 105: 70-76. [Abstract]
vom Saal, F.S., Timms, B.G., Montano, M.M., Palanza, P., Thayer, K.A., Nagel, S.C., Dahr, M.D., Ganjam, V.K., Parmigiani, S. and Welshons, W.V., 1997. Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proc. Natl. Acad. Sci. (USA) 94: 2056-2061.[Abstract]
Welshons, W.V., vom Saal, F.S. and Nagel, S.C., 1997. Relative binding affinity serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol – Response (Letter to the Editor). Environ. Health Perspect. 105: 571-572.
Ruh, M.F., Taylor, J.A., Howlett, A.C. and Welshons, W.V., 1997. Failure of cannabinoid compounds to stimulate estrogen receptors. Biochem. Pharmacol. 53: 35-41. [Abstract]
Gray, L.E., Kelce, W.R., Wiese, T., et al., and Welshons, W.V., 1997. Endocrine screening methods workshop report – Detection of estrogenic and androgenic hormonal and antihormonal activity for chemicals that act via receptor or steroidogenic enzyme mechanisms. Reproductive Toxicology 11: 719-750.
Judy, B.M. and Welshons, W.V., 1998. Cellular localization of receptors mediating actions of steroid hormones. In: Handbook of Physiology, Section 7: The Endocrine System, Volume I: Cellular Endocrinology, ed. P.M. Conn and H.M. Goodman, American Physiology Society, pp. 437-460.
Nagel, S.C., vom Saal, F.S. and Welshons, W.V., 1998. The effective free fraction of estradiol and xenoestrogens in human serum measured by whole cell uptake assays: physiology of delivery modifies estrogenic activity. Proc. Soc. Exp. Biol. Med. 217: 300-309. [Abstract]
Welshons, W.V., vom Saal, F.S. and Nagel, S.C., 1998. The importance of protocol design and data reporting to research on endocrine disruption – Response. Environ. Health Perspect. 106: A315-A317.
vom Saal, F.S., Cooke, P.S., Buchanin, D.L., Palanza, P., Thayer, K.A., Nagel, S.C., Parmigiani, S. and Welshons, W.V., 1998. A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production and behavior. Toxicol. Industrial Health 14: 239-260. [Abstract]
vom Saal, F.S., Welshons, W.V. and Hansen, L.G., 1998. Organochlorine levels and breast cancer. New England J. Med. 338: 988. [Abstract]
Welshons, W.V., Nagel, S.C., Thayer, K.A., Judy, B.M. and vom Saal, F.S., 1999. Low-dose bioactivity of xenoestrogens in animals: Fetal exposure to low doses of methoxychlor and other xenoestrogens increases adult prostate size in mice. Toxicol. Industrial Health 15: 12-25.
Nagel, S.C., vom Saal, F.S. and Welshons, W.V., 1999. Developmental effects of estrogenic chemicals are predicted by an in vitro assay incorporating modification of cell uptake by serum. J. Steroid Biochem. Molec. Biol. 69: 343-357.
Cunha, G.R., Forsberg, J.G., Golden, R., Haney, A., Iguchi, T., Newbold, R., Swan, S. and Welshons, W., 1999. New approaches for estimating risk from exposure to diethylstilbestrol. Environ. Health Perspect. 107 (Suppl 4): 625-630.
Laux, D.E., Curran, E.M., Welshons, W.V., Lubahn, D.B. and Huang, T.H.M., 1999. Hypermethylation of the Wilms’ tumor suppressor gene CpG island in human breast carcinomas. Breast Cancer Res. Treat. 56: 35-43.
Lee, A.V., Guler, B.L., Sun, X., Oesterreich, S., Zhang, Q.P., Curran, E.M. and Welshons, W.V., 2000. Oestrogen receptor is a critical component required for insulin-like growth factor (IGF)-mediated signalling and growth in MCF-7 cells. Eur J Cancer 36 (Suppl 4): 109-110.
vom Saal, F.S. and Welshons, W.V., 2000. NIH Panel Confirms That Endocrine Disrupting Chemicals Cause Effects at Very Low Doses. Risk Policy Report 7: 47-50.
Thayer, K.A., Ruhlen, R.L., Howdeshell, K.L., Buchanan, D.L., Cooke, P.S., Preziosi, D.E., Welshons, W.V., Haseman, J.K. and vom Saal, F.S., 2001. Altered prostate growth and daily sperm production in male mice exposed prenatally to sub-clinical doses of 17a-ethinyl estradiol. Human Reproduction 16: 988-996.
Gobert, G.N., Hueser, C.N., Curran, E.M., Sun, Q.-Y., Glinskii, S., Welshons, W.V., Eisenstark, A. and Schatten, H., 2001. Immunolocalization of NuMA and phosphorylated proteins during the cell cycle in human breast and prostate cancer cells as analyzed by immunofluorescence and postembedding immunoelectron microscopy. Histochemistry and Cell Biology 115: 381-395.
Oesterreich, S., Zhang, P., Guler, R.L., Sun, X., Curran, E.M., Welshons, W.V., Osborne, C.K. and Lee, A.V., 2001. Re-expression of estrogen receptor a in estrogen receptor a-negative MCF-7 cells restores both estrogen and insulin-like growth factor-mediated signaling and growth. Cancer Res. 61: 5771-5777.