Prenatal thyroxine treatment disparately affects peripheral and amygdala thyroid hormone levels

Pradeep Kumar Shukla, Laura J. Sittig, Brian M. Andrus, Daniel J. Schaffer, Kanchi K. Batra, Eva E. Redei

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

A prenatal hypothyroid state is associated with behavioral abnormalities in adulthood. Wistar Kyoto (WKY) rats exhibit hypothyroidism and increased depressive and anxiety-like behaviors. Thus, the WKY could illuminate the mechanisms by which the reversal of developmental hypothyroidism in humans and animals results in adult behavioral improvement. We examined the outcome of maternal thyroxine (T4) treatment on thyroid hormone-regulated functions and adult behavior of the WKY offspring. Pregnant WKY dams completed gestation with and without T4 administration and their adult male offspring were tested. Measures included depressive and anxiety-like behaviors, and thyroid hormone (TH) concentrations in both plasma and specific brain regions. In addition, the expression of two proteins affecting thyroid hormone trafficking and metabolism, monocarboxylate transporter 8 (MCT-8) and iodothyronine deiodinase type III (Dio3), and of several behavior-altering molecules, glucocorticoid receptor (GR), prepro-thyrotropin releasing hormone (prepro-TRH) and corticotrophin releasing hormone (CRH), were determined in the hippocampus and amygdala of the offspring. Prenatal T4 treatment of WKYs did not affect adult depressive behavior but increased anxiety-like behavior and decreased plasma levels of THs. In the hippocampus of males treated with T4 in utero, Dio3 and MCT-8 protein levels were increased, while in the amygdala, there were increases of free T4, MCT-8, GR, prepro-TRH protein and CRH mRNA levels. These results show that T4 administration in utero programs adult peripheral and amygdalar thyroid hormone levels divergently, and that the resulting upregulation of anxiety-related genes in the amygdala could be responsible for the exacerbated anxiety-like behavior seen in WKYs after prenatal T4 treatment.

Original languageEnglish (US)
Pages (from-to)791-797
Number of pages7
JournalPsychoneuroendocrinology
Volume35
Issue number6
DOIs
StatePublished - Jul 1 2010

Fingerprint

Amygdala
Thyroxine
Thyroid Hormones
Anxiety
Corticotropin-Releasing Hormone
Glucocorticoid Receptors
Hypothyroidism
Hippocampus
Proteins
Inbred WKY Rats
Up-Regulation
Mothers
Pregnancy
Messenger RNA
Brain
Genes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Prenatal thyroxine treatment disparately affects peripheral and amygdala thyroid hormone levels. / Shukla, Pradeep Kumar; Sittig, Laura J.; Andrus, Brian M.; Schaffer, Daniel J.; Batra, Kanchi K.; Redei, Eva E.

In: Psychoneuroendocrinology, Vol. 35, No. 6, 01.07.2010, p. 791-797.

Research output: Contribution to journalArticle

Shukla, Pradeep Kumar ; Sittig, Laura J. ; Andrus, Brian M. ; Schaffer, Daniel J. ; Batra, Kanchi K. ; Redei, Eva E. / Prenatal thyroxine treatment disparately affects peripheral and amygdala thyroid hormone levels. In: Psychoneuroendocrinology. 2010 ; Vol. 35, No. 6. pp. 791-797.
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