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Failure of bilateral paraventricular nuclear lesions to cause hypothalamic hypothyroidism in fetal sheep
T J McDonald1, G E Hoffman, P W Nathanielsz
1Department of Physiology, Cornell University College of Veterinary Medicine, Ithaca, New York 14853.
Abstract:
Concentrations of T4 indicative of a hyperthyroid state are present in fetal sheep plasma between 100 days gestational age (dGA) and parturition. Fetal pituitary stalk section studies indicate that, as in adults, these high fetal plasma T4 concentrations during pregnancy are controlled by the hypothalamus. We compared peripheral plasma T4 concentrations in fetal sheep with bilateral hypothalamic paraventricular nuclear (PVN) lesions (lesion group; n = 5) to fetal sheep with sham-PVN lesions (sham group; n = 4) at 131 and 146 dGA in the lesion group or at term (mean +/- SEM, 146 +/- 0.9 dGA) in the sham group. Bilateral hypothalamic PVN lesions or sham lesions were placed at 118-122 dGA. Baseline blood samples were taken between 1100-1500 h at 131 dGA in both groups, at term in the sham group, and at 146 dGA in the lesion group. In control sheep, TRH cells were found in the PVN and in a number of extra-PVN sites, and the median eminence received abundant TRH axons. In the lesion group, complete destruction of the PVN bilaterally was confirmed by histology. Extra-PVN TRH neurons remained intact in the lesioned sheep, and axons to the median eminence were reduced, but not eliminated. T4 concentrations in fetal plasma were not different in the lesion group and the sham group at 131 dGA (81 +/- 7 vs. 92 +/- 19 ng/ml) or at term (112 +/- 35 vs. 79 +/- 15 ng/ml), respectively. In contrast, fetal plasma concentrations of cortisol, which were not different in lesion and sham group fetuses at 131 dGA (1.7 +/- 0.3 vs. 1.0 +/- 0.2 ng/ml, respectively), were greatly reduced (P < 0.05) at 146 dGA in the lesion group compared to those in the sham group at term (2.0 +/- 0.5 vs. 58.8 +/- 11.5 ng/ml). We conclude that unlike in adult rats, the ovine fetal PVN is not required to maintain normal plasma T4 concentrations. The many TRH-positive cells that lie outside of the PVN in the fetal sheep appear to enable PVN-lesioned fetuses to remain euthyroid fetuses.