TABLE 4-1 Receptor-Mediated Developmental Toxicity

Receptor (official namea)

Endogenous Ligands

Developmentally Toxic Ligand and Modifier

Typical Effects

Recent References

Basic Helix-Loop-Helix Transcription Superfamily

Aryl hydrocarbon AHR

Unknown

Agonists: TCDD and related polycyclics

Cleft palate, hydronephrosis

Couture et al. 1990; Mimura et al. 1997; Abbott et al. 1998

Nuclear Hormone Receptors

Androgen AR (NR3C4)

Testosterone

Dihydro-testosterone

Agonists: 17 α-ethinyl-testosterone and related progestins

Antagonistsb: Flutamide

Agonists: Masculinization of female external genitals

Antagonists: Inhibition of Wolffian duct and prostate development and feminization of external genitals in males

Kassim et al. 1997

Estrogen

Estradiol

Agonist: DES

Agonist: various genital-tract defects in males and females

Cunha et al. 1999

ERa, ERb (NR3A1 and 2)

Antagonist: tamoxifen, clomiphene—weak

Glucocorticoid GR (NR3C1)

Cortisol

Agonists: cortisone, dexamethasone, triamcinolone

Cleft palate

Fawcett et al. 1996

Retinoic acid

RARα, β, and γ (NR1B1, 2, and 3)

All-trans & 9-cis retinoic acids

Agonists: numerous natural and synthetic retinoids

Antagonists: BMS493, AGN 193109 and others

Almost all organ systems can be affected

Collins and Mao 1999; Chazaud et al. 1999; Kochhar et al. 1998; Elmazar et al. 1997.

RARα, β, and γ (NR1B1, 2, and 3)

9-cis retinoic acid

 

 

 

Thyroid hormone TRa and b (NR1A1 and NR1A2)

Thyroxine (T4 and T3)

Antagonist: nitrophen

Lung, diaphragm, harderian-gland defects

Brandsma et al. 1994



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