Prenatal thyroxine treatment disparately affects peripheral and amygdala thyroid hormone levels.

Authors

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

Publication/Presentation Date

7-1-2010

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.

Volume

35

Issue

6

First Page

791

Last Page

797

ISSN

1873-3360

Published In/Presented At

Shukla, P. K., Sittig, L. J., Andrus, B. M., Schaffer, D. J., Batra, K. K., & Redei, E. E. (2010). Prenatal thyroxine treatment disparately affects peripheral and amygdala thyroid hormone levels. Psychoneuroendocrinology, 35(6), 791–797. https://doi.org/10.1016/j.psyneuen.2009.10.019

Disciplines

Medical Education | Medicine and Health Sciences

PubMedID

20005050

Department(s)

USF-LVHN SELECT Program, USF-LVHN SELECT Program Students

Document Type

Article