Fetal exposure to high maternal thyroid hormone (TH) levels causes central resistance to TH in adult humans and mice.

Fetal exposure to high maternal thyroid hormone (TH) levels causes central resistance to TH in adult humans and mice.

J Clin Endocrinol Metab. 2017 Jun 06;:

Authors: Srichomkwun P, Anselmo J, Liao XH, Hönes GS, Moeller LC, Alonso-Sampedro M, Weiss RE, Dumitrescu AM, Refetoff S

Abstract
Context: Fetuses exposed to the high thyroid hormone (TH) levels of mothers with resistance to thyroid hormone beta (RTHβ), due to mutations in the THRB gene, have low birth weight and suppressed TSH.
Objective: Determine if such exposure to high TH levels in embryonic life has a long-term effect into adulthood.
Design: Observations in humans with a parallel design on animals to obtain a preliminary information regarding mechanism.
Setting: University research centers.
Patients or other participants: Humans and mice with no RTHβ exposed during intrauterine life to high maternal TH levels from mothers who were, nevertheless, euthyroid due to RTHβ. Xοʋτρολσwere humans and mice of the same genotype but born to fathers with RTHβ αʋδμοτηερσwithout RTHβ and thus, with normal serum TH levels.
Interventions: TSH responses to stimulation with thyrotropin-releasing hormone (TRH) during adult life in humans and male mice before and after treatment with triiodothyronine (T3). Measurements of gene expression in anterior pituitaries, hypothalami and cerebral cortices of the mice.
Results: Adult humans and mice without RTHβ, exposed to high maternal TH in utero, showed persistent central resistance to TH as evidenced by reduced responses of serum TSH to TRH when treated with T3. In mice, anterior pituitary TSHβ and deiodinase 3 (D3) mRNAs, but not hypothalamic and cerebral cortex D3 were increased.
Conclusions: Adult humans and mice without RTHβ exposed in-utero to high maternal TH levels, have persistent central resistance to TH. This is likely mediated by the increased expression of D3 in the anterior pituitary, enhancing local T3 degradation.

PMID: 28586435 [PubMed - as supplied by publisher]

http://ift.tt/2r1Bzsj