Effects of octamethylcyclotetrasiloxane (D4) on the luteinizing hormone (LH) surge and levels of various reproductive hormones in female Sprague-Dawley rats.

The objectives of this study were to assess the potential for D(4) to suppress the pre-ovulatory lutenizing hormone (LH) surge, to block or delay ovulation, and to evaluate potential effects on reproductive hormones in rats. Female Sprague-Dawley Crl:CD (SD) IGS BR rats received whole-body vapor inhalation exposure to D(4) (0, 700, or 900ppm) 6h per day for 3 days. Trunk blood obtained on proestrus at 10a.m. was evaluated for levels of follicle stimulating hormone (FSH), estradiol (E2), estrone (E1), and progesterone (P4). Other rats had serial blood samples collected via cannula at 2, 4, 6, 8, and 10p.m. on the day of proestrus and plasma evaluated for LH and prolactin (PRL). Trunk blood was collected at 8a.m. of estrus and plasma evaluated for FSH, E2, E1, and P4. At 10a.m. on proestrus, significant increases in E1 levels in the 700 and 900ppm groups and significant increases in P4 levels in the 900ppm group were noted. At 8a.m. on estrus, significant increases in E1, E2, in the E1/E2 ratio and decreases in FSH were noted in the 700 and 900ppm groups. The major effect on the LH profile was observed most clearly when the rats were grouped by ovulatory status, animals that did or did not ovulate. Regardless of treatment, suppression of the LH surge correlated with blocked ovulation. The percentage of rats that ovulated was (700ppm, 42%; 900ppm, 31%) compared to controls (79%). Overall, the data indicate that high exposures to D(4) attenuated the pre-ovulatory LH surge and significantly decreased the portion of female rats that ovulated.

In vitro and in vivo evaluation of the estrogenic, androgenic, and progestagenic potential of two cyclic siloxanes.

The purpose of these experiments was to determine the potential estrogenic, androgenic, and progestagenic activity of two cyclic siloxanes, octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5). Receptor-binding experiments and a luciferase reporter gene assay were used to determine if the materials were able to bind and activate either the estrogen receptors (ERs) or progesterone receptors (PRs)-alpha or beta. The rat uterotrophic assay (RUA) for estrogenic activity and the Hershberger assay for androgenic activity were utilized as the in vivo assays. For the ER-binding studies, D4 was shown to bind to ERalpha but not to ERbeta. D5 did not bind to either of the two receptors. D4 activated the reporter gene at 10 microM, while D5 was considered negative in the estrogen reporter gene assay. Neither material was a ligand for the PRs. Both the RUA and Hershberger assays were conducted using whole-body inhalation of the two materials for 16 h/day. D4 resulted in a small but significant increase in both wet and blotted uterine weight as well as increases in both luminal and glandular epithelial cell height in both Sprague Dawley and Fischer 344 rats. D5 was negative in both rat strains, indicating that D5 does not possess estrogenic activity. Neither material possessed any significant antiestrogenic activity. Both materials were negative in the Hershberger assay indicating that neither material possesses any significant androgenic activity. Our studies have shown that D4 exhibits a low affinity for ERalpha in vitro and a weakly estrogenic response in vivo.