Developmental Changes in Rat Thyroid Responsiveness to Thyrotropin Administered by the Subcutaneous and Peroral Route 1

Abstract

Abstract

It has been demonstrated that orally administered thyrotropin (bovine, bTSH) evokes an increase in circulating T₄ and T₃ levels in 15-day-old suckling rat pups, but not in weaned animals. Because the feedback mechanisms of the hypothalamo-pituitary-thyroid axis change dramatically during the neonatal period, we chose to examine the efficacy of exogenous bTSH in eliciting a thyrostimulatory response via the subcutaneous (sc) or peroral (po) route in rat pups at 5, 8, 12, and 15 days postpartum. Suckling pups were divided into four groups and received one of the following: (i) 2 IU bTSH/100 g body wt administered sc; (ii) distilled H₂O (dH₂O) sc; (iii) 2 IU bTSH/100 g body wt given po; (iv) dH₂O po. Animals were sacrificed at Time 0 and 1,2, and 3 hr post-treatment, and the collected serum was analyzed for T₄ and T₃ by RIA. Maximum serum T₄ levels were attained at 2–3 hr post-treatment, and the T₄ response to sc-bTSH was significantly greater than that of the po-bTSH groups at all ages examined. This difference became progressively greater with increasing age, due to a persistent decline in T₄ responsiveness in animals receiving po-bTSH. No significant differences in T₄ or T₃ levels attained were observed in 8-day-old rat pups treated with rat vs bovine TSH, either sc or po. Percentage T₄ response (vs basal levels) steadily declined between Days 5 and 15 postpartum, in both sc- and po-bTSH treatment groups. Percentage T₃ responsiveness to sc-bTSH also declined between 5 and 12 days postpartum, after which time T₃ generation increased. Our results suggest that the neonatal rat is highly responsive to exogenous TSH late in the first week of life, and that the permeability of the gut at this stage of development further facilitates the impact of orally ingested TSH in the suckling.