Polychlorinated Biphenyls (PCBs) are endocrine disruptors that may act as thyroid hormone (TH) analogues/antagonists to alter the homeostasis of the thyroid axis. Recently, we have shown that perinatal exposure to Aroclor 1254 (A1254), a commercial mixture of more than 90 PCB congeners, leads to sex-specific changes of the thyrotropin-releasing hormone (TRH) mRNA synthesis in hypophysiotropic neurons of the hypothalamic paraventricular nucleus (PVN), and thyroid-stimulating hormone (TSH) serum levels in adult rats. As opposed to males, females showed no modifications in gene expression of hypophysiotropic TRH, but serum TSH significantly increased with respect to controls. To examine whether this central interference could be ascribed to specific PCB congeners, Sprague Dawley pregnant dams received 10 mg/kg of a mixture of PCB 138, 153, 180, and 126 every day from E10 to E19, and the same dose twice a week from P1 to P21 while breastfeeding. Both in post-weaned and adult female rats, serum levels of free 3,5,3´-triiodo-L-thyronine and free L-thyroxine remained unchanged with respect to controls. However, in adult females the perinatal treatment significantly increased the integrated optical density of immunoreactive (IR)-TRH prohormone (pro-TRH) in the median eminence (ME), decreased that of IR-TH receptor (THR)-β1 in hypophysiotrophic PVN neurons, and reduced percentage and number of IR-TSH cells in the anterior pituitary. We concluded that accumulation of pro-TRH in the ME was compatible with a reduced release of TRH; this reduction contributed to impair the survival of pituitary TSH cells, and less THR- β1 in the PVN was “compensated” by unchanged THR-α1 and - β2, yielding a stable amount of pro-TRH in the PVN. Collectively, our morphofunctional results suggest that perinatal exposure of female rats to PCBs induces an inadequate adaptation of the TRH-TSH axis in the adulthood, likely leading over time to central hypothyroidism. 

Endocrine disruptor, TRH, TSH, Central hypothyroidism