Transfer and metabolism of thyrotropin releasing hormone across the perfused human term placenta.
The transport and uptake of TRH was investigated in the maternal-fetal-placental unit of perfused human term placenta. The degradation of TRH in biological fluid was first determined by incubating [125I]TRH with 100 microL 50% maternal or cord sera with or without pretreatment with 200 microM of p-hydroxymercuriphenyl sulfonic acid (p-HMSA), a proline dipeptidase inhibitor. Transplacental transfer of TRH was then studied by adding 10 microCi of [125I]- or [3H]TRH to the maternal circulation of dually perfused isolated lobule of human term placenta with or without 200 microM p-HMSA. Creatinine was used as an internal marker. The rate of degradation of TRH (P < 0.001) and inhibition by p-HMSA were significantly higher in maternal than cord sera (P < 0.05). In the maternal circulation, TRH concentration declined rapidly from 100% at time 0 to 33.5 +/- 1.2% at 120 min. The fetal concentration increased from undetectable levels to a maximum of 1.8 +/- 0.3% at 120 min with a low feto-maternal ratio (0.08 +/- 0.02). Perfusion in the presence of p-HMSA, however, did not significantly change fetal concentration, or the maternal and fetal concentration-time integral levels of TRH. Chromatography of maternal, fetal, and placental homogenates showed that TRH was metabolized by the placenta into small molecular weight fragments predominantly released in the maternal circulation. These results suggest that human placenta acts as an enzymatic barrier to the free passage of TRH.
Bajoria
R
R
Institute of Obstetrics and Gynaecology, Royal Postgraduate Medical School, Queen Charlotte's and Chelsea Hospital, London, United Kingdom. rbajoria@rpms.ac.uk
Oteng-Ntim
E
E
Fisk
N M
NM
D001692:Biological Transport; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D010477:Perfusion; D010663:Phenylmercury Compounds / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D013973:Thyrotropin-Releasing Hormone / Q000097:blood / Q000378:metabolism*; D014316:Tritium
D007457:Iodine Radioisotopes; D010663:Phenylmercury Compounds; D014316:Tritium; C002910:4-hydroxymercuribenzenesulfonate; D013973:Thyrotropin-Releasing Hormone