Table 1.
Endocrine-disrupting pollutants with antiandrogenic toxicity through binding of the AR.
| Androgen-disruptor | Effects and associated mechanism | References |
|---|---|---|
| Diphenylmethanes | ||
| DDT | Decreased fertility, cryptorchidism; inhibition of DHT binding to AR, perturbed Ca++ mobilization, phosphorylation of c-ERB2/c-met; inhibition of p450scc | [9, 74, 130–134] |
| DDE | Cryptorchidism; inhibition of DHT binding to AR, MAPK pathway and PI3K activation, interacts with GPR30 | [9, 74, 133–136] |
| Methoxychlor | Inhibition of somatic growth, reduced accessory sex glandweight, elevation of serum prolactin; suppression ofLeydig cell function; inhibition of spermatogenesis, decreased seminal vesicles and epididymal weight, pubertal delay; induction of CYP28, CYP23A and CAR, alterations in germline DNA methylation, ER activation, antiandrogen and transgenerational effects | [82–85, 87] |
| Bisphenol A (BPA) | Aberrant development of prostate and urethra, increased anogenital distance, altered periductal stroma, increases susceptibility to prostate hormonal carcinogenesis, inhibition of DHT binding to AR, ligands mutated ARs | [93, 95, 134, 137–139] |
| Flutamides | ||
| Vinclozolin | Hypospadias, undescended testes, delayed puberty, prostate disease among subsequent generations; inhibition of DHT binding to AR, alters germline DNA methylation patterns | [100, 134, 140–143] |
| Linuron | Disruption of reproductive tract development; reduction of epididymal and accessory sex gland weight; increased serum estradiol and luteinizing hormone | [113] |
| Organochlorines | ||
| Lindan (γ-HCH) | Alterations in testes histology; inhibition of DHT binding to AR | [74, 117] |
| Procymidone | Fetal rat: shortened anogenital distance, permanent nipples, hypospadias, ectopic undescended testes, reduced weight and altered histology of prostate (and several other androgen-dependent tissues) | [8] |
| Dieldrin/aldrin | Reproductive performance affected at doses causing maternal intoxication; inhibition of DHT binding to AR | [74] |
| Phthalates | ||
| Butylbenzylphthalate | Reduced anogenital distance and weights of testes, epididymis, ventral prostate, and glans penis, female-like areolas/nipples, hypospadias, cryptorchidism, oligospermia, infertility; inhibition of DHT binding to AR | [80, 134, 144, 145] |
| Others | ||
| Nonyilphenol | MAPK pathway activation, PKC/cAMP modulation, reduced CYP1A1 expression; Reduction of 5α-reductase and 3α-hydroxysteroid-dehydrogenase activities; inhibition of DHT binding to AR | [7, 8] |