The ontogeny of [3H]5-hydroxytryptamine binding in the lamb: Effects of in vivo thyroidectomy

Abstract

The effects of congenital hypothyroidism in the late gestation ovine fetus include changes in serotonin concentrations in specific brain areas. To investigate possible ontogenic patterns of changes in 5-HT receptor function, we studied the binding characteristics of [3H]5-HT in the midbrain, hypothalamus and cerebral cortex in the late gestation ovine fetus and young lamb. We compared the binding characteristics of control fetuses to those of thyroidectomized fetuses, with or without thyroxine replacement therapy.In each of the areas examined, age-dependent changes in the receptor density (Bmax) for [3H]5-HT was observed. In cerebral cortex, Bmax was constant from 120 days gestation through the early neonatal period and increased significantly only at 25–30 days after birth. In hypothalamus, [3H]5-HT binding density decreased late in gestation (140–145 days) with a return after birth to values comparable to those at 120–125 and 130–135 days gestation. The midbrain also exhibited a significant age-dependent pattern of altered receptor density with a decrease in the 130–135 and 140–145 day gestational age groups compared to both younger and older lambs. In contrast, the affinity constant (Kd) for [3H]5-HT did not change over the ages evaluated in cerebral cortex or hypothalamus. In the midbrain. however, there was a significant increase in Kd at 1–5 days after birth compared to all other age groups. The ability of fetal thyroidectomy, with or without thyroxine replacement therapy, to alter patterns of [3H]5-HT binding was also tested. In the hypothyroid animals, examined at 130–135 days gestation, both the cerebral cortex and midbrain receptor affinities (Kd) were the same as control animals and animals of the same gestational age which had undergone throidectomy followed 10 days later by thyroxine treatment. In contrast, the receptor density (Bmax) for [3H]5-HT was increased significantly in the midbrain of both thyroidectomy animals and animals which had thyroidectomy plus thyroxine treatment.These data demonstrate marked patterns of ontogenic change in characteristics of [3H]5-HT binding, particularly in the midbrain region of this species. In addition, these studies support the hypothesis that changes in 5-HT receptor binding which result from hypothyroidism may be an index of thyroiddependent brain maturation.