Abstract
We determined the placental transfer of TSH in an in vitro model of dually perfused isolated lobule in 28 human term placentas by adding varying concentrations (5-60 μIU mL-1) of TSH as a single bolus dose to the closed maternal circulation. Transmembrane transfer of TSH was also studied by adding 45 μIU mL-1 to the maternal or fetal compartment of a dual chamber of fetal membranes in culture. Passage of freely diffusible markers creatinine and antipyrine were also studied in this model. TSH concentration was measured by third generation chemiluminescence assay with a sensitivity of 10 mIU mL-1. In the perfusion experiments, at physiologic concentrations the slow decline of TSH in the maternal circulation was associated with a small linear increase in fetal levels to 0.11 ± 0.04% of initial dose at 2 h. The placental transfer rate was 0.08 μIU min-1. Increasing maternal concentrations of TSH were associated with proportional increases in transfer rate (y = 0.002x; R2= 0.99) and placental uptake (y = 0.01x; R2 = 0.97). The placental permeability of TSH was 2.4·10-4 mL min-1 g-1 and was proportional to its coefficients of diffusion in water and molecular size. The transmembrane transfer and permeability of TSH was comparable to those of the placenta. We conclude that TSH crosses the human term placenta and fetal membranes sparingly.
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Abbreviations
- MAUC:
-
maternal area under the curve
- FAUC:
-
fetal area under the curve
- F/M:
-
fetomaternal
- TRH:
-
TSH-releasing hormone
References
Crowley P, Chalmers I, Keirse MJ 1990 The effects of corticosteroid administration before preterm delivery: An overview of the evidence from controlled trials. Br J Obstet Gynaecol 97: 11–25.
Roti E, Gnudi A, Braverman LE 1993 The placental transport, synthesis and metabolism of hormones and drugs which affect thyroid function. Endocr Rev 4: 131–149.
Ballard PL, Ballard RA, Creasy RK, Padbury J, Polk DH, Bracken M, Moya FR, Gross I 1992 Plasma thyroid hormones and prolactin in premature infants and their mothers after prenatal treatment with thyrotropin-releasing hormone. Pediatr Res 32: 673–678.
Crowther CA, Alfirevic Z 1995 Antenatal thyrotropin-releasing hormone prior to preterm delivery. In: Keirse MJMC, Renfrew MJ, Crowther CA, Neilson JP (eds) Cochrane Database of Systematic Reviews-Pregnancy and Childbirth Module, Version 1.2, Disk Issue 2, Record 4749
Bajoria R, Oteng-Natim E, Fisk NM 1996 Transfer and metabolism of thyrotropin releasing hormone across the perfused human term placenta. J Clin Endocrinol Metab 81: 3476–3482.
Bajoria R, Fisk NM 1997 Maternal-fetal transfer of thyrotropin releasing hormone: effect of maternal dose and concentration. Pediatr Res 41: 674–681.
Bajoria R, Peek M, Fisk NM Maternal to fetal transfer of thyrotrophin releasing hormone in vivo. Am J Obstet Gynaecol, in press
Bajoria R, Ryder TA, Fisk NM 1997 Transport and metabolism of thyrotrophin releasing hormone across the fetal membrane. J Clin Endocrinol Metab 82: 3399–3407.
Heinrichs C, de-Zegher F, Vansnick F, Vokaer A, Christophe C, Frankenne F 1994 Fetal hypopituitarism: perinatal endocrine and morphological studies in two cases. Acta Paediatr 83: 448–451.
Yoshida K, Sakurada T, Takahashi T, Furuhashi N, Kaise K, Yoshinaga K 1986 Measurement of TSH in human amniotic fluid: diagnosis of fetal thyroid abnormality in utero. Clin Endocrinol 25: 313–318.
Robuschi G, Braverman LE, Emanuele R, d'Amato L, Gardini E, Foscolo MS, Gualerzi C, Benassi L, Gnudi A, Roti E 1985 Amniotic fluid thyrotropin (TSH) following maternal administration of thyrotropin releasing hormone. J Perinat Med 13: 219–226.
Hollingsworth DR, Alexander NM 1983 Amniotic fluid concentrations of iodothyronines and thyrotropin do not reliably predict fetal thyroid status in pregnancies complicated by maternal thyroid disorders or anencephaly. J Clin Endocrinol Metab 57: 349–355.
Bain MD, Copas DK, Landon MJ, Stacey TE 1988 In vivo permeability of the human placenta to inulin and mannitol. J Physiol 399: 313–319.
Thornburg KL, Burry KJ, Adams AK, Kirk EP, Faber JJ 1988 Permeability of placenta to inulin. Am J Obstet Gynecol 158: 1165–1169.
Bajoria R, Contractor SF 1992 Transfer of heparin across the human perfused placental lobule. J Pharm Pharmacol 44: 952–959.
Eaton BM, Browne MJ, Contractor SF 1985 Maternal to fetal movement of creatinine as a measure of perfusion efficiency and diffusional transfer in the isolated human placental lobule. Placenta 6: 341–346.
Bajoria R, Oteng-Natim E, Peek M, Fisk NM 1997 Pharmacokinetics and pharmacodynamics of TRH during pregnancy. Obstet Gynaecol 90: 187–192.
Roseblade CK, Sullivan MH, Khan H, Lumb MR, Elder MG 1990 Limited transfer of prostaglandin E2 across the fetal membrane before and after labor. Acta Obstet Gynecol Scand 69: 399–403.
Heinegard D, Tiderstrom G 1973 Determination of serum creatinine by a direct colorimetric method. Clin Chim Acta 43: 305–310.
Brodie BB, Axelrod J, Soberman R, Levy BB 1949 The estimation of antipyrine in biological materials. J Biol Chem 179: 25–31.
Klein MD, Drongowski RA, Linhardt RJ, Langer RS 1982 A colorimetric assay for chemical heparin in plasma. Anal Biochem 124: 59–64.
Bajoria R, Contractor SF 1993 Maternal-fetal transfer of warfarin across an in vitro model of perfused placenta; effect of albumin binding. Br J haematol 84: 59
Contractor SF, Eaton BM, Stannard PJ 1983 Uptake and fate of exogenous immunoglobulin G in the perfused human placenta. J Reprod Immunol 5: 265–273.
Reynolds F, Knott C 1989 Pharmacokinetics in pregnancy and placental drug transfer. Oxf Rev Reprod Biol 11: 389–449.
Dancis J, Jansen V, Levitz M 1976 Transfer across perfused human placenta. IV. Effect of protein binding on free fatty acids. Pediatr Res 10: 5–10.
Contractor SF, Stannard PJ 1983 The use of AIB transport to assess the suitability of a system of human placental perfusion for drug transport studies. Placenta 4: 19–30.
Ridgway EC, Weintraub BD, Maloof F 1974 Metabolic clearance and production rates of human thyrotropin. J Clin Invest 53: 895–903.
Edwards D, Jones CJ, Sibley CP, Nelson DM 1993 Paracellular permeability pathways in the human placenta: a quantitative and morphological study of maternal-fetal transfer of horseradish peroxidase. Placenta 14: 63–73.
Illsley NP, Hall S, Penfold P, Stacey TE 1985 Diffusional permeability of the human placenta. Contr Gynecol Obstet 13: 92–97.
Schneider H, Sodha RJ, Progler M, Young MPA 1985 Permeability of the human placenta for hydrophilic substances studied in the isolated dually in vitro perfused lobe. Contr Gynecol Obstet 13: 98–103.
Ching MS, Mihaly GW, Morgan DJ, Date NM, Hardy KJ, Smallwood RA 1987 Low clearance of cimetidine across the human placenta. J Pharmacol Exp Ther 241: 1006–1009.
Willis DM, O'Grady JP, Faber JJ, Thornburg KL 1986 Diffusion permeability of cyanocobalamin in human placenta. Am J Physiol 250:R459–R464.
Stulc J 1988 Is there control of solute transport at placental level. Placenta 9: 19–26.
Bain MD, Copas DK, Taylor A, Landon MJ, Stacey TE 1990 Permeability of the human placenta in vivo to four non-metabolized hydrophilic molecules. J Physiol 431: 505–513.
McCoshen JA, Barc J 1985 Prolactin bioactivity following decidual synthesis and transport by amniochorion. Am J Obstet Gynecol 153: 217–223.
Kent AS, Sullivan MH, Sun MY, Zosmer A, Elder MG 1993 Effects of interleukin-6 and tumor necrosis factor-alpha on prostaglandin production by cultured human fetal membranes. Prostaglandins 46: 351–359.
Fortunato SJ, Menon RP, Swan KF, Menon R 1996 Inflammatory cytokine (interleukins 1, 6 and 8 and tumor necrosis factor-α) release from cultured human fetal membranes in response to endotoxic lipopolysaccharide mirrors amniotic fluid concentrations. Am J Obstet Gynecol 174: 1855–18561.
Kent AS, Sullivan MH, Elder MG 1994 Transfer of cytokines through human fetal membranes. J Reprod Fertil 100: 81–84.
Morris C, Sullivan MH, Elder MG 1992 Transfer and metabolism of platelet-activating factor by fetal membranes, amnion and chorio-decidua. Br J Obstet Gynaecol 99: 895–898.
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Bajoria, R., Fisk, N. Permeability of Human Placenta and Fetal Membranes to Thyrotropin-Stimulating Hormone in Vitro. Pediatr Res 43, 621–628 (1998). https://doi.org/10.1203/00006450-199805000-00010
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DOI: https://doi.org/10.1203/00006450-199805000-00010
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