A CRITICAL PERIOD FOR THE ROLE OF THYROID-HORMONE IN DEVELOPMENT OF RENAL ALPHA-ADRENERGIC RECEPTORS

Adrenergic input influences renal cell replication/differentiation and the development of excretory function. Kidney cells make adrenoceptor s before the arrival of the majority of nerve terminals, and the curre nt study examines whether thyroid hormone plays a role in receptor dev elopment. Propylthiouracil (PTU) was given to pregnant and neonatal ra ts from gestational d 17 through postnatal d 5, a treatment that obtun ds thyroid hormone levels throughout the first 2-3 wk postpartum. The PTU group showed significant deficits in the number of alpha(1)-recept ors, and values resolved to normal in parallel with hormone level reco very. The effects were not secondary to alterations in cell differenti ation or growth, as the period of receptor abnormalities did not corre spond to that of growth inhibition. Similarly, the effects were select ive for the alpha(1)-receptor, as no comparable effects were seen for total membrane protein or for alpha(2)-receptors. The role of thyroid hormone in alpha(1)-receptor ontogeny involved a critical developmenta l window; later in development neither treatment with PTU nor with lar ge doses of thyroid hormone had any impact on alpha(1)-receptors. Stud ies of mRNAs encoding the alpha(1)-receptor subtypes indicated that hy pothyroidism targets the alpha(1a)-subtype, which has been implicated in the transduction of neurotrophic signals; alpha(1a)-receptor mRNA a lso showed the largest proportional developmental increase compared wi th those encoding other alpha(1)-subtypes. Accordingly, thyroid hormon e is likely to set the stage for the subsequent trophic control of ren al development by neural input, and hypothyroidism during this critica l window can be expected to result in abnormal renal functional develo pment and increased perinatal risk.