Environmental
Health Perspectives Volume 107, Number 2, February 1999
Developmental Synergism of Steroidal Estrogens in Sex
Determination
Judith M. Bergeron, Emily Willingham, C. Todd Osborn, III, Turk
Rhen, and David Crews
Institute of Reproductive Biology, Department of Zoology,
University of Texas at Austin, Austin, TX 78712 USA
Abstract
Gonadal sex in the red-eared slider turtle, Trachemys
scripta, is determined by incubation temperature during
embryonic development. Evidence suggests that temperature
determines sex by influencing steroid hormone metabolism and/or
sensitivity: steroidogenic enzyme inhibitors or exogenous sex
steroid hormones and their man-made analogs override (or enhance)
temperature effects on sex determination. Specifically,
nonaromatizable androgens and aromatase inhibitors induce testis
differentiation at female-producing temperatures, whereas
aromatizable androgens and estrogens induce ovary differentiation
at male-producing temperatures. Moreover, natural estrogens and
temperature synergize to produce more females than would be
expected if estrogens and temperature had purely additive effects
on sex determination. In this study, we use sex reversal of turtle
embryos incubated at a male-producing temperature to examine
synergism among steroidal estrogens: estrone, 17ß-estradiol,
and estriol. A low dose of 17ß-estradiol (200 ng) showed
significant synergism when administered with a single low dose of
estriol (10 ng). Likewise, a single low dose of estrone (250 ng)
had a synergistic effect when combined with the same low dose of
estriol (10 ng). We conclude that the weak natural estrogens
estrone and 17ß-estradiol synergize with a low dose of the
more potent estriol to reverse gonadal sex during the critical
period of sexual differentiation. These results suggest that weak
environmental estrogens may also synergize with stronger natural
estrogens. Key words: estradiol, estriol, estrogen, estrone,
synergy, temperature-dependent sex determination. Environ Health
Perspect 107:93-97 (1999). [Online 8 January 1999]
Address correspondence to D. Crews, Institute of Reproductive
Biology, Department of Zoology, University of Texas at Austin,
Austin, TX 78712 USA.
The authors wish to thank R. Vohra and Y. Tasnif for technical
assistance, J. Branch for graphics, and J.A. McLachlan and S.F.
Arnold for discussions on the research design and interpretation of
the results. This work was partially supported by NIH T32 MH18837,
NIMH Research Scientist Award, and NSF IBN 9723617 to D.C.
Received 6 May 1997; accepted 20 August 1998.