Developmental changes in rat thyroid responsiveness to thyrotropin administered by the subcutaneous and peroral route

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.