Perinatal exposure to Aroclor 1254 disrupts thyrotropin-releasing hormone mRNA expression in the paraventricular nucleus of male and female rats

Toxicology. 2024 Nov:508:153935. doi: 10.1016/j.tox.2024.153935. Epub 2024 Aug 27.

Abstract

Polychlorinated biphenyls (PCBs) are industrial pollutants that act as endocrine disruptors and alter thyroid function. However, it is still unclear whether PCBs can affect hypothalamic thyrotropin releasing hormone (Trh) mRNA expression through TH signaling disruption. As salt-loading dehydration induces tertiary hypothyroidism in the hypothalamic parvocellular paraventricular nuclei (paPVN), and perinatal exposure to Aroclor 1254 (A1254) disrupts the hydric balance in rats, we hypothesized that TRH synthesis could be altered during dehydration in TRH neurons that control the hypothalamic-pituitary-thyroid (HPT) axis activity in rats perinatally exposed to A1254. We examined Trh mRNA expression in the paPVN and the response to salt-loading dehydration (hyperosmotic (hyper) stress) in the progeny of Wistar pregnant rats receiving 0 mg/kg BW (control) or 30 mg/kg BW A1254 daily from gestational days 10-19. Three-month-old offspring were subjected to normosmotic or hyper conditions and Trh mRNA, glucocorticoid receptor (GR) mRNA expression were measured in the PVN by RT-PCR. TRH mRNA and TRH+ neurons were measured in the paPVN by fluorescent in situ hybridization (FISH). As expected, Trh mRNA levels were decreased in the paPVN of male and female rats in the hyper group. Basal Trh mRNA expression and serum TSH were decreased in male rats in the A1254 group. Notably, Trh mRNA levels were further decreased in the paPVN of male and female A1254 + hyper rats, in which the GR mRNA expression was significantly decreased. These results support the hypothesis that perinatal exposure to A1254 results in inadequate adaptive response of the HPT axis in adulthood and contributes to dysregulation of the HPT axis response to salt-loading dehydration.

Keywords: Endocrine disruptor; HPT axis; Salt-loading dehydration; Trh mRNA.

MeSH terms

  • Animals
  • Chlorodiphenyl (54% Chlorine)* / toxicity
  • Endocrine Disruptors / toxicity
  • Female
  • Male
  • Paraventricular Hypothalamic Nucleus* / drug effects
  • Paraventricular Hypothalamic Nucleus* / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • Rats
  • Rats, Wistar*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Thyrotropin-Releasing Hormone* / genetics
  • Thyrotropin-Releasing Hormone* / metabolism

Substances

  • Thyrotropin-Releasing Hormone
  • RNA, Messenger
  • Chlorodiphenyl (54% Chlorine)
  • Receptors, Glucocorticoid
  • Endocrine Disruptors