Cardiacα-adrenergic Receptor Expression is Regulated by Thyroid Hormone During a Critical Developmental Period

Although thyroid hormone is obligatory for the development of cardiacβ-adrenergic receptors, it is difficult to assign a specific role for the hormone in receptor ontogeny becauseβ-receptor expression is affected similarly in the adult. We have determined whether thyroid hormone plays a role in receptor development by evaluatingα1-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 ofα1-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 inα1-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 examiningα2-receptors, which disappear over the first three postnatal weeks; delayed differentiation caused by propylthiouracil would slow the decline inα2-receptors, whereas accelerated differention caused by triiodothyronine would hasten the decline. Instead, the effects were similar to those onα1-receptors: perinatal propylthiouracil administration reduced, and neonatal triiodothyronine administration enhanced,α2-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.