Abstract
Objective: The purpose of this study was to investigate the transport of inhibin A and to determine its effects on fetal vascular pressure at elevated levels in the human placenta using 125I -labeled synthetic glycoprotein.
Methods: Synthetic inhibinAwas prepared and was shown to be consistent with the natural form by high-pressure liquid chromatography (HPLC) and molecular weight determination by gas-chromatography mass spectrometry. The standardized Na125I process yielded 125I -labeled inhibin A with a radioactivity of 106 cpm/μg. This compound was placed in the human placenta in maternal–fetal and fetal–maternal studies using antipyrine and 14C -labeled inulin as controls to determine the bidirectional transfer of the compound.
Results: Maternal–fetal and fetal–maternal clearance indices were 0.045± 0.003 and 0, respectively. In eight placentas there was no evidence of vascular pressure changes due to the presence of up to 5000 pg of inhibin A.
Conclusions: There is minimal maternal–fetal transfer and no detectable fetal–maternal transfer in normotensive and pregnancy-induced hypertensive placentas. In addition, there are no pressure changes in the fetal vascular system due to the clinically significant levels of inhibin A.
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Selected References
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- Bawdon R. E. The ex vivo human placental transfer of the anti-HIV nucleoside inhibitor abacavir and the protease inhibitor amprenavir. Infect Dis Obstet Gynecol. 1998;6(6):244–246. doi: 10.1002/(SICI)1098-0997(1998)6:6<244::AID-IDOG4>3.0.CO;2-B. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Billiar R. B., Smith P., Falcone T. Identification of immunoreactive inhibin in human and baboon fetal serum at term as free alpha-subunit(s). J Clin Endocrinol Metab. 1995 Nov;80(11):3173–3179. doi: 10.1210/jcem.80.11.7593422. [DOI] [PubMed] [Google Scholar]
- Brandes J. M., Tavoloni N., Potter B. J., Sarkozi L., Shepard M. D., Berk P. D. A new recycling technique for human placental cotyledon perfusion: application to studies of the fetomaternal transfer of glucose, inulin, and antipyrine. Am J Obstet Gynecol. 1983 Aug 1;146(7):800–806. doi: 10.1016/0002-9378(83)91081-5. [DOI] [PubMed] [Google Scholar]
- Casey B., Bawdon R. E. Ex vivo human placental transfer of trovafloxacin. Infect Dis Obstet Gynecol. 2000;8(5-6):228–229. doi: 10.1155/S1064744900000326. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Challier J. C. Criteria for evaluating perfusion experiments and presentation of results. Contrib Gynecol Obstet. 1985;13:32–39. [PubMed] [Google Scholar]
- Kettel L. M., Roseff S. J., Bangah M. L., Burger H. G., Yen S. S. Circulating levels of inhibin in pregnant women at term: simultaneous disappearance with oestradiol and progesterone after delivery. Clin Endocrinol (Oxf) 1991 Jan;34(1):19–23. doi: 10.1111/j.1365-2265.1991.tb01730.x. [DOI] [PubMed] [Google Scholar]
- Kim J. K., Tsen M. F., Ghetie V., Ward E. S. Identifying amino acid residues that influence plasma clearance of murine IgG1 fragments by site-directed mutagenesis. Eur J Immunol. 1994 Mar;24(3):542–548. doi: 10.1002/eji.1830240308. [DOI] [PubMed] [Google Scholar]
- Krummen L. A., Woodruff T. K., DeGuzman G., Cox E. T., Baly D. L., Mann E., Garg S., Wong W. L., Cossum P., Mather J. P. Identification and characterization of binding proteins for inhibin and activin in human serum and follicular fluids. Endocrinology. 1993 Jan;132(1):431–443. doi: 10.1210/endo.132.1.7678220. [DOI] [PubMed] [Google Scholar]
- Magee K. P., Bawdon R. E. Ex vivo human placental transfer and the vasoactive properties of hydralazine. Am J Obstet Gynecol. 2000 Jan;182(1 Pt 1):167–169. doi: 10.1016/s0002-9378(00)70508-4. [DOI] [PubMed] [Google Scholar]
- Sairam M. R., Ramasharma K., Li C. H. Synthetic peptide with inhibin-like activity preferentially inhibits follitropin secretion in comparison with lutropin-releasing hormone antagonists. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2043–2046. doi: 10.1073/pnas.84.7.2043. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneider H., Panigel M., Dancis J. Transfer across the perfused human placenta of antipyrine, sodium and leucine. Am J Obstet Gynecol. 1972 Nov 15;114(6):822–828. doi: 10.1016/0002-9378(72)90909-x. [DOI] [PubMed] [Google Scholar]
- Silver H. M., Lambert-Messerlian G. M., Star J. A., Hogan J., Canick J. A. Comparison of maternal serum total activin A and inhibin A in normal, preeclamptic, and nonproteinuric gestationally hypertensive pregnancies. Am J Obstet Gynecol. 1999 May;180(5):1131–1137. doi: 10.1016/s0002-9378(99)70606-x. [DOI] [PubMed] [Google Scholar]
- Yamashiro D., Li C. H., Ramasharma K., Sairam M. R. Synthesis and biological activity of human inhibin-like peptide-(1-31). Proc Natl Acad Sci U S A. 1984 Sep;81(17):5399–5402. doi: 10.1073/pnas.81.17.5399. [DOI] [PMC free article] [PubMed] [Google Scholar]
