Ontogeny and Effects of Thyroid Hormone on β1-Adrenergic Receptor mRNA Expression in Ovine Fetal Kidney Cortex

Abstract

Objective: Previous studies indicate that thyroidectomy (TX) decreases renin gene expression in ovine fetal renal cortex in late gestation. Fetal ovine renin-containing renocortical cells become increasingly responsive to β-adrenergic stimulation as gestation proceeds. Increases in plasma thyroid hormone concentrations parallel this change, suggesting that there is a positive developmental relationship between the two. To examine this hypothesis, we determined the ontogeny of β₁-adrenergic receptor (β₁R) mRNA expression, and the effect of thyroid hormone on in vivo and in vitro expression in fetal sheep.

Methods: Renocortical tissue was obtained from naive, TX, and sham-operated fetuses to determine β₁R mRNA levels. Renin-containing renocortical cells from TX or sham fetuses were treated with isoproterenol (Iso) or forskolin (FSK) fory analysis of cellular cyclic adenosine monophophate (cAMP) levels. Renocortical cells from naive fetuses were treated with triiodothyronin (T₃) to assess cellular β₁R mRNA levels. Fetal plasma thyroxine (T₄) level was determined.

Results: Renocortical β₁R mRNA expression increased significantly between 100 and 140 days' gestational age (dGA), while TX attenuated this increase (p <.01). Renocortical cellular cAMP levels were higher in sham compared to TX fetuses following incubation with Iso or FSK (P <.05). Cells incubated with T₃ exhibited significantly increased β₁R mRNA expression (P <.05).

Conclusion: The data suggest that thyroid hormone may be involved in modulating ovine fetal renocortical β₁R gene expression during development. We speculate that the increased β₁R mRNA expression in renal cortical cells as development progresses may mediate the increases in renin gene response to β-adrenergic stimulation in late gestation.

Keywords

Thyroid hormone β1R mRNA kidney fetal development

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