Steroidal teratogens

Brown, D. and Keeler, R. F. (1978a). Structure-activity relation of steroid teratogens. 1. Jervine ring system, J. Agric. Food Chem., 26 561-563. 

Brown, D., and Keeler, R. F. 1978. Structure-Activity Relation of Steroid Teratogens 3. Solanidan-epimers. Journal of Agricultural and Food Chemistry 26 566-569. 

Habert, R. and Picon, R. (1984). Testosterone, dihytrostestosterone and estradiol-17/ levels in maternal and fetal plasma and in fetal testes in the rat. J. Steroid Biochem. 21 183-198. Hansen, D.K. and Hodes, M.E. (1983). Comparative teratogenicity of phenytoin among several inbred strains of mice. Teratology 28 175-179. 

The structural features of the solanum alkaloids are based on two primary skeletal configurations solanidane, with or without glycoside functionalities, as featured by the toxic and teratogenic steroidal alkaloids a-chaconine and a-solanine with the indolizidine type E-F ring (Figure 2.7a) and the spirosolane... 

Steroidal alkaloids found in Veratrum spp. and Solanum spp. with their relative teratogenic potency, as determined in a hamster bioassay. 

Figure 2.7 Two steroidal alkaloids from Solanum spp. (a) a-chaconine, with teratogenic activity, and (b) tomatidine, non-teratogenic alkaloid.

Figure 2.9 (a) Cyclopamine, steroidal alkaloid teratogen from Veratrum spp., and (b) zygacine, non-teratogenic alkaloid from Zygadenus spp. 

Gaffield, W. and Keeler, R.F. (1996). Steroidal alkaloid teratogens molecular probes for investigation of craniofacial malformations, J. Toxicol. Toxin Rev., 15, 303-326. 

Retinoic acid works through a family of retinoic acid receptors. Activated retinoic acid receptors act as transcription factors, just as activated steroid receptors do (chapter 20), and alter the transcription of genes affecting cell division and survival. This underlies both the teratogenic potential and the therapeutic utilities of these potent molecules. 

Biotin deficiency in experimental animals is teratogenic, and a number of the resultant birth defects resemble human birth defects. Up to half of pregnant women have elevated excretion of 3-hydroxy-isovaleric acid (Section 11.4), which responds to supplements of biotin, in the first trimester, suggesting that marginal stams may be common in early pregnancy and may be a factor in the etiology of some birth defects. This may be the result of increased catabolism of biotin as a result of steroid induction of biotin catabolic enzymes there is increased excretion of bisnorbiotin and biotin sulfoxide (Zempleni and Mock, 2000a Mock et al., 2002). 

SAFETY PROFILE Poison by intraperitoneal route. Moderately toxic by subcutaneous route. An experimental teratogen. Other experimental reproductive effects. Mutation data reported. A steroid. When heated to decomposition it emits vet toxic fumes of SOx and NOx. See also CORTISONE. 

SAFETY PROFILE An experimental teratogen. Other experimental reproductive effects. A steroid. When heated to decomposition it emits acrid smoke and fumes. 

SAFETY PROFILE Confirmed carcinogen with experimental carcinogenic, neoplastigenic, tumorigenic, and teratogenic data. A promoter. Human reproductive effects by ingestion fertility effects. Experimental reproductive effects. Human mutation data reported. A steroid hormone much used in medicine. When heated to decomposition it emits acrid smoke and irritating fumes. 

Keeler RF, Binns W. Teratogenic compounds of Veratrum californicum (Durand). V. Comparison of cyclopian effects of steroidal alkaloids from the plant and structurally related compounds from other sources. Teratology. 1968 1(1) 5-10. 

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