Thyrotropin-Releasing Hormone-Stimulated Pituitary and Thyroid Gland Responsiveness and 3,5,3′-Triiodothyronine Suppression in Fetal and Neonatal Lambs*

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Abstract
To evaluate the development of the pituitary thyroid axis and negative feedback control of TSH [thyrotropin] secretion, ovine TSH (oTSH) and T4 [thyroxine] were measured by radioimmunoassay in plasma samples obtained before and 15, 30, 60, 120 and 240 min after an i.v. bolus injection of TRH [thyrotropin-releasing hormone, thyroliberin] in fetal lambs between 105-113 days gestation (group I) and between 125-129 days gestation (group II); newborn lambs also were injected between 7-12 days of age (group III). In each group, the TRH injection and plasma-sampling protocols were repeated 14-18 h after an i.v. injection of T3 [triiodothyronine]. Plasma oTSH concentrations increased in all animals in response to TRH injection. Neither the difference between the peak and baseline plasma concentrations (.DELTA.TSH) nor the integrated area under the plasma concentration-response curves (.intg.TSH) correlated with gestational age. Both responses correlated with baseline oTSH concentrations (r [correlation coefficient] = 0.72 and r = 0.73, respectively; P < 0.02 for both) and both (.DELTA.TSH and .intg.TSH) were significantly decreased in group III newborn animals (P < 0.05 for both). T3 did not suppress the oTSH response. The plasma T4 response (.DELTA.T4) and the T4 response in relationship to the TSH response (.DELTA.T4/.intg.TSH) increased with gestational age (r = 0.70 and P < 0.02 for .DELTA.T4; r = 0.66 and P < 0.03 for .DELTA.T4/.intg.TSH). The mean .DELTA.T4/.intg.TSH for group III newborn animals was significantly greater than the mean for the older group II fetuses (P < 0.04). TRH-evoked TSH release in sheep apparently increases during fetal life, depending primarily on hypothalamic pituitary maturation rather than gestational age. The TSH response to TRH is significantly reduced in newborn lambs. T3 fails to suppress the TSH response to TRH in the fetus and newborn, suggesting immaturity of the negative feedback system for the control of TSH release. Thyroid gland sensitivity to TSH stimulation appears to increase throughout fetal and neonatal life.