Maternofetal transfer of thyrotrophin-releasing hormone: effect of concentration and mode of administration.

We studied the effect of maternal concentration and mode of administration on transfer rate of TSH-releasing hormone (TRH) in an in vitro model of dually perfused isolated lobule of human term placenta. Varying concentrations (4-40 microg dL(-1)) of TRH were added either to the open maternal circulation to mimic an infusion or as a single bolus dose to the closed maternal circulation. TRH was measured by RIA. Perfusion efficiency in each experiment was determined by using antipyrine and creatinine as diffusable markers. At a concentration equivalent to the usual clinical dose of 400 microg, transplacental transfer of TRH was 0.4 +/- 0.1%, with an fetal/maternal ratio of 0.01 +/- 0.003. Placental clearance rate (y = 0.07x; R2 = 0.97; p < 0.001; n = 28) and uptake of TRH (y = 0.40x; R2 = 0.95; p < 0.001) in the closed experiments increased exponentially with increasing maternal concentration. Placental clearance (y = 0.05x; R2 = 0.99; p < 0.001; n = 30), and uptake of TRH (y = 0.35x; R2 = 0.98; p < 0.01) under steady state also correlated with maternal TRH concentration. For a given concentration, placental clearance and uptake of TRH was comparable whether given as a bolus or an infusion. We conclude that TRH is transferred sparingly across the human term placenta and its transfer rate is a function of the maternal concentration of TRH and not its mode of administration.