Endocrine Abstracts

Physiological determination of the hypothalamic pituitary thyroid axis set point

Roy E Weiss

Departments of Medicine and Pediatrics, University of Chicago, Chicago, Illinois, USA.

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Regulation of thyroid hormone (TH) levels in blood is controlled by feedback at the level of the pituitary and hypothalamus. It has been suggested that the set-point of either turning on or off the release of TSH and TRH, respectively is due to multiple factors including intrauterine exposure to TH. We have utilized the TH receptor (TR) β disrupted mouse (TRβ−/−) as model to study the effect of maternal levels of TH on newborn thyroid function. The rationale of this study was to determine if the high TH level of dams (TRβ−/−) on normal pups (TRβ+/−) or the normal TH levels of unaffected dams (TRβ+/−) relatively low for euthyroid hyperthyroxinemic (TRβ−/−) pups have an effect on the hypothalamic pituitary thyroid (HPT) axis. Results demonstrated that TRβ−/− mice born to euthyroxinemic mothers (TRβ+/−) had lower serum TSH values at birth and higher peak serum TSH at 2 weeks compared to RTH mice born to RTH dams. Furthermore, euthyroxinemic mice (TRβ+/−) born to RTH mothers (high T4 levels) had persistent suppression of serum TSH without a peak as seen in TRβ+/− born to TRβ+/− mothers. The TRβ+/− pups born to RTH dams (TRβ−/−) had a blunted serum TSH peak response to TRH after birth. In order to assess subtle abnormalities in thyroid function, TRH stimulation test were performed in 60–80 days old mice treated with L-T₃. TSH was measured before and after the administration of TRH. A paradoxical increase in TSH in response to TRH was seen in normal mice born to RTH dams suggesting a change in their HPT set point. Although mechanisms may exist to regulate fetal exposure to maternal TH levels we speculate that early in embryogenesis maternal TH levels may affect pup maturation and pituitary thyroid axis development.

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Endocrine Abstracts (2009) 19 S22