Effects of maternal iodine deficiency and thyroidectomy on basal neuroendocrine function in rat pups

Abstract

We have used in situ hybridization histochemistry to investigate the effects of maternal thyroidectomy and chronic maternal iodine deficiency on basal neuroendocrine function in rat pups. Specifically, we have measured hypothalamic thyrotrophin-releasing hormone (TRH) and pituitary thyroid-stimulating hormone (TSH) expression together with circulating levels of tri-iodothyronine (T3) in rat pups delivered from and suckled by thyroidectomized or iodine-deficient dams. Because of the close interaction between the thyroid, adrenal and growth hormone axes, we have also examined hypothalamic corticotrophin-releasing hormone (CRH) and growth hormone-releasing hormone (GRH) transcripts at the same time points: birth, 1 month and 2 months of age. Three weeks after surgical thyroidectomy, adult female Sprague-Dawley rats proved unable to carry pups to term and lactate successfully. Pups delivered from thyroidectomized dams given a small replacement dose of T3 during pregnancy were significantly lighter than controls (84 +/- 3%) and had markedly depressed plasma T3 levels (36 +/- 6% of control). Hypothalamic CRH and GRH transcript levels were significantly decreased in pups at birth (to 8 +/- 2.5% and 24 +/- 8% of control respectively) but had returned to normal by 1 month after delivery. Pituitary TSH transcript levels and hypothalamic levels of TRH transcripts, however, were similar to those of controls. Only one of seven dams fed a low-iodine diet for 6 months produced live pups, and these were too few in number to produce significant data. Dams fed a low-iodine diet from 4 months before mating, however, did produce live pups and although they were not significantly lighter than control pups at birth, by 1 month after birth, they were significantly lighter (72 +/- 3% of controls). Circulating T3 levels were not significantly different from control at any time point examined. Hypothalamic TRH levels were significantly elevated at birth (451 +/- 138% of control), but this difference was not maintained at 1 or 2 months after birth despite the lactating dams being maintained on the low-iodine diet. Pituitary TSH levels showed an upward trend at all time points that reached significance at 1 month after birth (204 +/- 19%; P < 0.05). Hypothalamic CRH and GRH transcript levels were not different from controls at any time point. In summary, chronic iodine deficiency or thyroidectomy with low-level T3 replacement in Sprague-Dawley rats markedly impaired fertility and the ability to carry pups to term, and produced an unexpectedly modest up-regulation of the hypothalamo-pituitary-thyroid axis and down-regulation of the hypothalamo-pituitary-adrenal axis.