Table 3.
Endocrine-disruptors chemicals and putative mechanisms of action associated with central precocious puberty
| Category | Chemicals related with pubertal disorders | Main sources | Putative mechanisms involved in pubertal disorders, especially in CPP | Possible molecular targets in GnRH network in rodent models (259, 260, 261) |
|---|---|---|---|---|
| Bisphenols | Bisphenol A | Plasticizers, drink and food containers, building materials | - Estrogenic activity by binding to estrogen receptors - Impairment of kisspeptin neurons maturation at the arcuate nucleus |
- At hypothalamic nuclei: estrogen receptor-∞, estrogen receptor-ß, kisspeptin,
GABA, glutamate, RFamide-related peptide 3 - Effects on DNA methylation (Dnmt1, Dnmt3a, Dnmt3b, Esr1) - Effects on histone posttranslational modifications |
| Phthalates | Phthalates compounds | Plasticizers, consumer products (especially cosmetics), food packing, toys | - Estrogenic activity by binding to estrogen receptors - Antiandrogenic activity - Increased kisspeptin activity |
At hypothalamic nuclei: estrogen receptor-∞, estrogen receptor-ß, kisspeptin |
| Pesticides | Persistent (DDT and DDE) and nonpersistent | Agricultural applications | - Estrogenic activity by binding to estrogen receptors - Antiandrogenic activity by altering sex steroid synthesis enzymes |
- At hypothalamic nuclei: estrogen receptor-∞, estrogen receptor-ß, glutamate
- Effects on DNA methylation (Esr1) |
| Heavy metal | Mercury | Diet-delivered, especially in fish and seafoods | Accumulation in the hypothalamus, the pituitary, and the gonads | |
| Essential oil | Lavender oil components | Lavender-fragranced products | Premature breast development: estrogenic and antiandrogenic properties of components of lavender essential oil | |
| Pharmaceutical | Paracetamol | Analgesics and antipyretics | - Inhibition of prostaglandins signalling possibly disrupting physiological
roles of prostaglandins in the development of the brain and the gonads - Increase of estrogen production - Inhibition of androgen production |
|
| Parabens | Parabens | Consumer products (cosmetics and personal care) | Estrogenic activity | At hypothalamic nuclei: estrogen receptor-∞ |
| Flame retardants | Polybrominated diphenyl ethers (PBDE) | Plastics, textiles, furniture | Estrogenic and androgenic properties | |
| Polychlorinated biphenyl (PCB) | Mixtures | Oils, additives | Action on estrogen receptors and neurotransmitter receptors | - At hypothalamic nuclei: estrogen receptor-∞, estrogen receptor-ß, kisspeptin
- Effects on miRNAs |
| Phytoestrogens | Genistein | Soybean, oats | Estrogenic properties | At hypothalamic nuclei: estrogen receptor-ß, kisspeptin |
| Dioxins | Dioxin | Industrialized products | Antiandrogenic activity |