Abstract
Extract: Experiments were conducted to assess late and persistent endocrine changes in the progeny of rats born of and/or nursed by thyroidectomized (Tx) dams. Forty-five female rats were radiothyroidectomized several weeks before mating with normal males, and compared with the progeny of 26 control females. In all, 248 progeny were studied when adult.
Tx dams had significantly reduced fertility (87% of controls), increased pup (11% versus 0) and maternal mortality (27% versus 0), and smaller litters (6.5 versus 11.8 pups/litter).
It was shown that the offspring of thyroidectomized female rats had delayed eye opening (15.3 versus 14.3 days), smaller weaning (40.4 versus 54.4 g) and adult body weights (230 versus 260 g), smaller pituitary glands (12.2 versus 14.0 mg), and enlarged thyroid glands (14.2 versus 12.4 mg). Ovarian and testicular weights were decreased (73.9 versus 83.7 mg and 3.2 versus 3.6 g, respectively). The serum thyroid stimulating hormone (TSH) concentrations were increased from 53.8 to 84.4 μU/ml in the males. The pituitary TSH contents were not significantly altered, and the serum TSH response to thyrotropin releasing hormone (TRH) was normal. These persistent effects differed from the late effects of both fetal and neonatal hypothyroidism and neonatal underfeeding. Cross-fostering experiments showed that the diminished weaning weights were the result of the pups being nursed by the hypothyroid dams. The increased nursing mortality and the pituitary and thyroidal changes were the result of prenatal influences produced by the hypothyroid dams, since being nursed by a normal foster dam did not prevent them. The persistently enlarged thyroid glands and the elevated serum TSH in the male offspring of thyroidectomized dams suggested a permanent alteration in the set point of pituitary-thyroid regulation as the consequence of maternal hypothyroidism.
Speculation: It is speculated that the intrauterine environment provided by the pregnant hypothyroid mother produces permanent alterations in endocrine regulatory mechanisms in the offspring. It is suggested that the transplacental transfer of fetal thyroxine (T4) to the hypothyroid mother places a burden on the fetal pituitary-thyroid axis that permanently alters its function in these progeny. We have shown previously that during a critical perinatal period, T4 excess or deficiency can permanently alter hypothalamo-pituitary regulatory function in the offspring.
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Bakke, J., Lawrence, N., Robinson, S. et al. Endocrine Studies of the Untreated Progeny of Thyroidectomized Rats. Pediatr Res 9, 742–748 (1975). https://doi.org/10.1203/00006450-197509000-00012
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DOI: https://doi.org/10.1203/00006450-197509000-00012
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