Cardiac alpha-adrenergic receptor expression is regulated by thyroid hormone during a critical developmental period.
Although thyroid hormone is obligatory for the development of cardiac beta-adrenergic receptors, it is difficult to assign a specific role for the hormone in receptor ontogeny because beta-receptor expression is affected similarly in the adult. We have determined whether thyroid hormone plays a role in receptor development by evaluating alpha 1-adrenergic receptors, which in the adult are downregulated by thyroid hormone. Propylthiouracil given from gestational day 17 through postnatal day 5 caused significant deficits in the number of alpha 1-receptors and values resolved to normal in parallel with hormone level recovery. When propylthiouracil was administered later (postnatal days 11 through 15) only a transient deficit in alpha 1-receptor binding was seen; hyperthyroidism (triiodothyronine) could still evoke stimulation of receptor expression at this stage. The effects on receptor expression were distinguished from general effects on cell differentiation by examining alpha 2-receptors, which disappear over the first three postnatal weeks; delayed differentiation caused by propylthiouracil would slow the decline in alpha 2-receptors, whereas accelerated differentiation caused by triiodothyronine would hasten the decline. Instead, the effects were similar to those on alpha 1-receptors: perinatal propylthiouracil administration reduced, and neonatal triiodothyronine administration enhanced, alpha 2-receptor binding sites. Thus, thyroid hormone plays a role in the control of cardiac adrenergic receptor expression during a critical development period, with conjoint regulation of the multiple receptor subtypes present within the tissue. As adrenergic stimulation is important in maintaining cardiac function in the perinatal period, alterations of thyroid status during this period can be expected to result in abnormal reactivity and increased perinatal risk.
Metz, LD; Seidler, FJ; McCook, EC; Slotkin, TA
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