Abstract: 458

HIGHER SERUM TESTOSTERONE IN THE ESTROGEN RECEPTOR– KNOCKOUT (ERKO) MOUSE IS DUE TO INCREASED LEYDIG CELL STEROIDOGENESIS.

BT Akingbemi^{1 *}, CS Rosenfeld^{2 *}, DB Lubahn^{2 3} , MP Hardy^{1 *}
Center for Biomedical Research, Population Council, New York, NY. ¹
Department of Animal Sciences, University of Missouri, Columbia, MO. ²
Departments of Biochemistry, and Child Health, University of Missouri, MO. ³

Leydig cells express both isoforms of the estrogen receptor (ER and ER). Male ERKO mice lack ER and become infertile as adults but have higher serum testosterone (T) levels compared to wild-type, WT C57BL/6J/129 litter mates. Whether the elevation in serum T is caused by increases in Leydig cell number or T biosynthesis by individual Leydig cells is not known. The present study measured serum T and its production normalized to Leydig cell number. Leydig cells were incubated in the presence and absence of ovine LH (100 ng/ml). T concentrations were measured by RIA (n = 4 replicate experiments). Serum T levels were significantly higher in ERKO (5.8 ± 0.4, ng/ml) than in WT (2.9 ± 0.07, p < 0.001). Basal T production by purified ERKO Leydig cells (61.8 ± 2.6, ng/10⁶ cells h^-1) was also higher than WT (33.2 ± 3.8, p < 0.001). LH–stimulated T production (ng/10⁶ cells h^-1) by ERKO and WT Leydig cells was, respectively, 620 ± 27.2 and 406.9 ± 38.3, representing 10- and 12-fold increases over basal levels (p < 0.001). The observed increase in T biosynthesis correlates with serum T, both were 2-fold higher than control, and is most likely due to elevated serum LH seen in ERKO males. Direct estrogen effects on Leydig cell steroidogenesis are not excluded, but 0.5 and 1.0 M 17–estradiol did not inhibit T production by ERKO or WT Leydig cells in vitro. We conclude that individual ERKO Leydig cells have an increased capacity for T biosynthesis compared to control, and suggest that infertility is due to factors other than T, such as fluid build up in the excurrent ducts. Supported by NIH grants FO5 TW 05350, ES 08272 and HD 32588.

    This abstract is being presented on Tuesday, August 3 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.