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Updated: Jul 6, 2026

In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
Hypothalamic-pituitary axis and peripheral tissue responses to TRH stimulation and liothyronine suppression tests in
Gustavo Leopoldo Rodrigues Dare1, Margaret de Castro, Lea Maria Zanini Maciel
1Division of Endocrinology, Department of Internal Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
Objective:
To reevaluate the responses of thyrotropin-releasing hormone (TRH) stimulation test in baseline condition as well as after the administration of graded supraphysiological doses of liothyronine (L-T(3)) in normal subjects.
Design:
To assess various parameters related to the hypothalamic-pituitary axis and peripheral tissue responses to L-T(3) in 22 normal individuals (median age: 30.5 years). Subjects were submitted to an intravenous TRH test at baseline condition and also to the oral administration of sequential and graded doses of L-T(3) (50, 100, and 200 microg/day), each given over 3 days, at an outpatient clinic. Blood samples were obtained for thyrotropin (TSH) and prolactin (PRL) at basal and then 15, 30, and 60 minutes after the TRH injection. Effects of L-T(3) administration on cholesterol, creatine kinase, retinol, ferritin, and sex hormone-binding globulin (SHBG) were also measured at basal and after the oral administration of L-T(3).
Main Outcome:
TRH administration resulted in an increase of 4- to 14-fold rise in serum TSH (8.3 +/- 2.5-fold), and in a slight rise in serum PRL concentrations (3.8 +/- 1.5-fold). Administration of graded doses of triiodothyronine (T(3)) resulted in a dose-dependent suppression of TSH and PRL. Basal thyroxine-binding globulin (TBG) and cholesterol levels decreased, and ferritin and SHBG increased after L-T(3) administration, while creatine kinase and retinol did not change throughout the study. There was a positive correlation between basal TSH and TSH peak response to TRH at basal condition and after each sequential L-T(3) doses. On the other hand, TSH peak response to the TRH test did not predict cholesterol, TBG, ferritin, or SHBG values.
Conclusion:
Using the current methods on hormone and biochemical analysis, we standardized the response of many parameters to TRH stimulation test after sequential and graded T(3) suppression test in normal subjects. Our data suggest that the evaluation of the responses of the hypothalamus-pituitary axis to TRH test as well as the impact of L-T(3) on peripheral tissues were not modified by the current methods.
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