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Semin Reprod Med 2001; 19(1): 063-068
DOI: 10.1055/s-2001-13912
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

A Proposed Role for hCG in Clinical Obstetrics

James T. Kurtzman1 , H. Wilson2 , Ch. V. Rao2
  • 1Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of California, Irvine Medical Center, Orange, California
  • 2Department of Obstetrics and Gynecology, University of Louisville, Louisville, Kentucky
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Publikationsdatum:
31. Dezember 2001 (online)

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ABSTRACT

The role of human chorionic gonadatropin (hCG) in the maintenance of early pregnancy is well known. Recent data suggests that hCG may play a role in the maintenance of the later stages of pregnancy as well, by directly and indirectly promoting uterine quiescence. If hCG acts as an endogenous tocolytic in normal pregnancy, then it may be an ideal candidate for therapy of preterm labor as well. We present compelling in vitro as well as in vivo data, which support the role of hCG in the maintenance of normal uterine quiescence. Additionally, we will present in vivo and in vitro data that confirms the ability of hCG to directly promote relaxation of uterine contractions. This review provides a basis for future study of the use of hCG in clinical obstetrics. Given the limited effectiveness of tocolytic therapies available at the time, hCG may provide a promising pharmacological approach to the pervasive problem of preterm labor in human pregnancy. While further work is needed, initial data strongly support this novel use of hCG in clinical obstetrics.

KEYWORD

hCG - pregnancy - uterine quiescence - preterm labor - tocolytic therapy

REFERENCES

  • 1 Gonik B, Creasy R K. Preterm labor: its diagnosis and management.  Am J Obstet Gynecol . 1986;  154 3-8
    PubMedSuche in Google Scholar
  • 2 Lockwood C J, Senyei A E, Dische M R. Fetal fibronectin in cervical and vaginal secretions defines a patient population at high risk for preterm delivery.  N Engl J Med . 1991;  325 669-674
    CrossrefPubMedSuche in Google Scholar
  • 3 Nageotte M P, Hollenbach K A, Vanderwahl B A, Hutch K M. Fetal fibronectin in patients at increased risk for premature birth.  Am J Obstet Gynecol . 1994;  170 20-25
    PubMedSuche in Google Scholar
  • 4 Iams J D, Johnson F F, Sonek J, Sachs L, Gebauer C, Samuels P. Cervical competence as a continuum: a study of ultrasonographic cervical length and obstetrical performance.  Am J Obstet Gynecol . 1995;  172 1097-1103
    Suche in Google Scholar
  • 5 Iams J D, Goldenberg R L, Meis P J. The length of the cervix and cervix and the risk of spontaneous preterm delivery.  N Engl J Med . 1996;  334 567-572
    CrossrefPubMedSuche in Google Scholar
  • 6 Goldenberg R L, Iams J D, Mercer B M. The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births.  Am J Public Health . 1998;  88 233-238
    CrossrefPubMedSuche in Google Scholar
  • 7 Gordon M C, Iams J D. Magnesium sulfate.  Clin Obstet Gynecol . 1995;  38 706-712
    PubMedSuche in Google Scholar
  • 8 Hill W C, Gill P J, Katz M. Maternal paralytic ileus as a complication of magnesium sulfate tocolysis.  Am J Perinatol . 1985;  2 47-48
    PubMedSuche in Google Scholar
  • 9 Lockwood C T. Calcium-channel blockers in the management of preterm labor.  Lancet . 1997;  350 1339-1340
    CrossrefPubMedSuche in Google Scholar
  • 10 Garite T J, Keegan K A, Freeman R K, Nageotte M P. A random trial of ritodrine tocolysis versus expectant management in patients with premature rupture of membranes at 25-30 weeks of gestation.  Am J Obstet Gynecol . 1987;  157 388-393
    PubMedSuche in Google Scholar
  • 11 Pierce J G, Parsons T F. Glycoprotein hormones: structure and function.  Annu Rev Biochem . 1981;  50 465-495
    CrossrefPubMedSuche in Google Scholar
  • 12 Rodway M R, Rao C V. A novel perspective on the role of human chorionic gonadotropin during pregnancy and in gestational trophoblastic disease.  Early Pregnancy Biol Med . 1995;  1 176-187
    PubMedSuche in Google Scholar
  • 13 Rao C V. The beginning of a new era in reproductive biology and medicine: expression of low levels of functional luteinizing hormone/human chorionic gonadotropin receptors in nongonadal tissues.  J Physiol Pharmacol . 1996;  47 41-53
    PubMedSuche in Google Scholar
  • 14 Rao C V, Sanfilippo J S. New understanding in the biochemistry of implantation: potential direct roles of luteinizing hormone and chorionic gonadotropin.  Endocrinology . 1997;  7 108-111
    PubMedSuche in Google Scholar
  • 15 Rao C V. Potential novel roles of luteinizing hormone and chorionic gonadotropin during early pregnancy in women.  Early Pregnancy Biol Med . 1997;  3 1-9
    PubMedSuche in Google Scholar
  • 16 Loosfelt H, Misrahi M, Atger M. Cloning and sequencing of porcine LH-HCG receptor cDNA: variants lacking transmembrane domain.  Science . 1989;  245 525-528
    PubMedSuche in Google Scholar
  • 17 McFarland K C, Sprengel R, Phillips H S. Lutropin-choriogonadotropin receptor: an unusual member of the G-protein coupled receptor family.  Science . 1989;  245 494-499
    CrossrefPubMedSuche in Google Scholar
  • 18 Ziecik A J, Stanchev P D, Tilton J E. Evidence for the presence of luteinizing hormone/human chorionic gonadotropin-binding sites in the porcine uterus.  Endocrinology . 1986;  119 1159-1163
    PubMedSuche in Google Scholar
  • 19 Reshef E, Lei Z M, Rao C V, Pridham D D, Chegini N, Luborsky J L. The presence of gonadotropin receptors in nonpregnancy human uterus, human placenta, fetal membranes, and decidua.  J Clin Endocrinol Metab . 1990;  70 421-430
    PubMedSuche in Google Scholar
  • 20 Lei Z M, Toth P, Rao C V, Pridham D. Novel coexpression of human chorionic gonadotropin (hCG)/human luteinizing hormone receptors and their ligand HCG in human fallopian tubes.  J Clin Endocrinol Metab . 1993;  77 863-872
    CrossrefPubMedSuche in Google Scholar
  • 21 Toth P, Rao C V. Direct novel regulation of cyclooxygenase and prostacyclin synthase by human chorionic gonadotropin in the human amnion.  Trophoblast Res . 1994;  8 503-514
    PubMedSuche in Google Scholar
  • 22 Lei Z M, Rao C V. Gonadotropin receptors in human fetoplacental unit: implications for hCG as an intracrine, paracrine and endocrine regulator of human fetoplacental function.  Trophoblast Res . 1992;  6 213-224
    PubMedSuche in Google Scholar
  • 23 Shi Q J, Lei Z M, Rao C V. Novel role of human chorionic gonadotropin in differentiation of human cytotrophoblasts.  Endocrinology . 1993;  132 1387-1395
    CrossrefPubMedSuche in Google Scholar
  • 24 Licht P, Cao H, Lei Z M, Rao C V, Merz W M. Novel self-regulation of human chorionic gonadotropin biosynthesis in term pregnancy human placenta.  Endocrinology . 1993;  133 3014-3025
    CrossrefPubMedSuche in Google Scholar
  • 25 Rao C V, Li X, Toth P, Lei A Z, Cook V D. Novel expression of functional human chorionic gonadotropin/human luteinizing hormone receptor gene in human umbilical cords.  J Clin Endocrinol Metab . 1993;  77 1706-1714
    CrossrefPubMedSuche in Google Scholar
  • 26 Lei Z M, Rao C V, Komyei J L, Licht P, Hiatt E S. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain.  Endocrinology . 1993;  132 2262-2270
    CrossrefPubMedSuche in Google Scholar
  • 27 Lei Z M, Rao C V. Novel presence of luteinizing hormone/ human chorionic gonadotropin receptors and the down-regulation action of hCG on gonadotropin releasing hormone gene expression in immortalized hypothalamic GTI-7 neurons.  Mol Endocrinol . 1994;  8 1111-1121
    CrossrefPubMedSuche in Google Scholar
  • 28 Toth P, Lukacs H, Hiatt E S, Reid K H, Iyer V, Rao C V. Administration of human chorionic gonadotropin affects sleep wake phases and other association behaviors in cycling female rats.  Brain Res . 1994;  654 181-190
    CrossrefPubMedSuche in Google Scholar
  • 29 Chegini N, Lei Z M, Rao C V, Hansel W. Cellular distribution and cycle phase dependency of gonadotropin and eicosanoids binding sites in bovine corpora lutea.  Biol Reprod . 1991;  45 506-513
    PubMedSuche in Google Scholar
  • 30 Toth P, Li X, Rao C V. Expression of functional human chorionic gonadotropin/human luteinizing hormone receptor gene in human uterine arteries.  J Clin Endocrinol Metab . 1994;  79 307-315
    CrossrefPubMedSuche in Google Scholar
  • 31 Lincoln S, Lei Z M, Rao C V, Yussman M A. The expression of human chorionic gonadotropin/human luteinizing hormone receptors in ectopic human endometrial implants.  J Clin Endocrinol Metab . 1992;  75 1140-1144
    CrossrefPubMedSuche in Google Scholar
  • 32 Lei Z M, Rao C V, Lincoln S, Ackermann D M. Increased expression of human chorionic gonadotropin/human luteinizing hormone receptors in adenomyosis.  J Clin Endocrinol Metab . 1993;  76 763-768
    CrossrefPubMedSuche in Google Scholar
  • 33 Lin J, Lei Z M, Lojun S, Rao C V, Satyaswaroop P G, Day Jr G T. Increased expression of luteinizing hormone/human chorionic gonadotropin receptor gene in human endometrial carcinomas.  J Clin Endocrinol Metab . 1994;  79 1483-1491
    CrossrefPubMedSuche in Google Scholar
  • 34 Singh M, Zuo J, LiX, et al. The decreased expression of functional human chorionic gonadotropin/luteinizing hormone receptor gene in human uterine leiomyomas.  Biol Reprod . 1995;  53 899-904
    PubMedSuche in Google Scholar
  • 35 Bemardini L, Moretti-Rojas L, Brush F J, Balmaceda J P. Status of hCG/LH receptor and G proteins in human endometrium during artificial cycles of hormone replacement therapy.  J Soc Gynecol Invest . 1995;  2 630-635
    CrossrefPubMedSuche in Google Scholar
  • 36 Han S W, Lei Z M, Sanfilippo J S, Rao C V. Human chorionic gonadotropin as a new regulator of human endometrial stroma cells differentiation into decidua. The Program of the Endocrine Society Annual Meeting, 1995, abstract P2-84
  • 37 Zuo J, Lei Z M, Rao C V. Human myometrial chorionic gonadotropin/luteinizing hormone receptors in preterm and term deliveries.  J Clin Endocrinol Metab . 1994;  79 907-911
    CrossrefPubMedSuche in Google Scholar
  • 38 Bonnamy P J, Benhaim A, Leymarie P. Estrous cycle-related changes of high affinity luteinizing hormone/human chorionic gonadotropin binding sites in the uterus.  Endocrinology . 1990;  26 1264-1269
    PubMedSuche in Google Scholar
  • 39 Bonnamy P J, Benham A, Leymarie P. Uterine luteinizing hormone/human chorionic gonadotropin-binding sites in the early pregnant rat uterus: evidence for total occupancy in the periimplantation period.  Endocrinology . 1993;  132 1240-1246
    CrossrefPubMedSuche in Google Scholar
  • 40 Friedman S, Gurevich M, Shemesh M. Bovine cyclic endometrium contains high-affinity luteinizing hormone/ human chorionic gonadotropin binding sites.  Biol Reprod . 1995;  52 1020-1026
    PubMedSuche in Google Scholar
  • 41 Kornyei J, Lei Z M, Rao C V. Human myometrial smooth muscle cells are novel targets of direct regulation by human chorionic gonadotropin.  Biol Reprod . 1993;  49 1149-1157
    PubMedSuche in Google Scholar
  • 42 Zhou X L, Lei Z M, Rao C V. Regulation of cyclooxygenase-2 gene expression by chorionic gonadotropin in mucosal cells from human fallopian tubes.  Endocrinology . 1997;  137 2929-2937
    PubMedSuche in Google Scholar
  • 43 Han S W, Lei Z M, Rao C V. Up-regulation of cyclooxygenase-2 gene expression by chorionic gonadotropin during the differentiation of human endometrial stromal cells into decidua.  Endocrinology . 1996;  137 1791-1797
    CrossrefPubMedSuche in Google Scholar
  • 44 Toth P, Li X, Rao C V. Expression of functional human chorionic gonadotropin/human luteinizing hormone receptor gene in human uterine arteries.  J Clin Endocrinol Metab . 1994;  79 307-315
    CrossrefPubMedSuche in Google Scholar
  • 45 Lei Z M, Reshef E, Rao C V. The expression of human chorionic gonadotropin/luteinizing hormone receptors in human endometrial and myometrial blood vessels.  J Clin Endocrinol Metab . 1992;  75 65:1-6
    PubMedSuche in Google Scholar
  • 46 Ambrus G, Rao C V. Novel regulation of pregnant human myometrial smooth muscle cell gap junctions by human chorionic gonadotropin.  Endocrinology . 1994;  135 2772-2779
    CrossrefPubMedSuche in Google Scholar
  • 47 How H, Huang Z H, Zuo J, Lei Z M, Spinnato J A, Rao C V. Myometrial estradiol and progesterone receptor changes in preterm and term pregnancies.  Obstet Gynecol . 1995;  86 936-940
    CrossrefPubMedSuche in Google Scholar
  • 48 Csapo A L. Effects of progesterone, prostaglandin F2alpha, and its analogue ICI 81008 on the excitability and threshold of the uterus.  Am J Obstet Gynecol . 1976;  124 367-378
    PubMedSuche in Google Scholar
  • 49 Beck P, Adler P, Szlachter N, Goldsmith L T, Steinetz B G, Weiss G. Synergistic effect of human relaxin and progesterone on human myometrial contractions.  Int J Gynaecol Obstet . 1982;  20 141-144
    CrossrefPubMedSuche in Google Scholar
  • 50 Eta E, Ambrus G, Rao C V. Direct regulation of human myometrial contractions by human chorionic gonadotropin.  J Clin Endocrinol Metab . 1994;  79 1582-1586
    CrossrefPubMedSuche in Google Scholar
  • 51 Willeke K, Hennemann H, Dahl E, Jungbluth S, Heynkes R. The diversity of connexin genes encoding gap junctional proteins.  Eur J Cell Biol . 1991;  56 1-7
    PubMedSuche in Google Scholar
  • 52 Stagg R B, Fletcher W HI. The hormone-induced regulation of contact-dependent cell-cell communication by phosphorylation.  Endocr Rev . 1990;  11 302-325
    PubMedSuche in Google Scholar
  • 53 Bennett M VL, Barrio L C, Bargielto T A, Sprat D C, Hertzberg E, Saez J C. Gap junctions: new tools, new answers, new questions.  Neuron . 1991;  6 305-320
    CrossrefPubMedSuche in Google Scholar
  • 54 Haefliger J A, Bruzzone R, Jenkins N A, Gilbert D J, Copeland N G, Paul D L. Four novel members of the connexin family of gap junction proteins. Molecular cloning, expression and chromosome mapping.  J Biol Chem . 1992;  267 2057-2064
    PubMedSuche in Google Scholar
  • 55 Iyer E C, Kistler J, Paul D L, Goodenough J. Antisera directed against connexin43 peptides react with a 43-kD protein localized to gap junctions in myocardium and other tissues.  J Cell Biol . 1989;  108 595-605
    CrossrefPubMedSuche in Google Scholar
  • 56 Lang L M, Beyer E C, Schwartz A L, Gitlin J D. Molecular cloning of a rat uterine gap junction protein and analysis of gene expression during gestation.  Am J Physiol . 1991;  260 E787-E793
    PubMedSuche in Google Scholar
  • 57 Garfield R E, Blennerhassett M G, Miller S M. Control of myometrial contractility: role and regulation of gap junctions.  Oxf Rev Reprod Biol . 1988;  10 436-490
    PubMedSuche in Google Scholar
  • 58 Garfield R E, Hayashi R H. Appearance of gap junctions in the myometrium of women during labor.  Am J Obstet Gynecol . 1981;  140 254-260
    PubMedSuche in Google Scholar
  • 59 Tabb T, Thilander G, Grover A, Jertzberg E, Garfield R E. An immunochemical and immunocytologic study of the increase in myometrial gap junctions (and connexin 43) in rats and humans during pregnancy.  Am J Obstet Gynecol . 1992;  167 559-567
    PubMedSuche in Google Scholar
  • 60 Sakai N, Tabb T, Garfield R E. Modulation of cell-to-cell coupling between myometrial cells of the human uterus during pregnancy.  Am J Obstet Gynecol . 1992;  167 472-480
    PubMedSuche in Google Scholar
  • 61 Chow L, Lye S J. Expression of the gap junction protein connexin-43 is increased in the human myometrium toward term and the onset of labor.  Am J Obstet Gynecol . 1994;  170 778-795
    PubMedSuche in Google Scholar
  • 62 Uzumcu M, Coskun S, Jaroudi K, Hollanders J M. Effect of human chorionic gonadotropin on cytokine production from human endometrial cells in vitro.  Am J Reprod Immunol . 1998;  40 83-88
    PubMedSuche in Google Scholar
  • 63 Kurtzman J T, Spinnato J A, Goldsmith L J. Human chorionic gonadotropin exhibits potent inhibition of preterm delivery in a small animal model.  Am J Obstet Gynecol . 1999;  181 853-857
    PubMedSuche in Google Scholar
  • 64 Kurtzman J, Jones E, Goldsmith L J. Inhibition of preterm delivery by human chorionic gonadotropin is associated with down-regulation of myometrial gap junctions [abstract].  Am J Obstet Gynecol . 2000;  187 S201
    PubMedSuche in Google Scholar
  • 65 Tozzozada M K. Does hCG have a direct effect on the human myometrium [abstract]?.  Fertil Steril . 1998;  70(suppl 3) S68
    PubMedSuche in Google Scholar
  • 66 Hay D L. Placental histology and the production of human chorionic gonadotropin and its subunits in pregnancy.  Br J Obstet Gynaecol . 1988;  95 1268
    PubMedSuche in Google Scholar
  • 67 Abdalla I S, Prineas R J, Neaton J D. The effect of the dose of human chorionic gonadotropin and the type of gonadotropin stimulation on oocyte recovery rates in an in vitro fertilization program.  Fertil Steril . 1987;  48 958
    PubMedSuche in Google Scholar
  • 68 Friedman J M, Polifka J E. Teratogenic Effects of Drugs: A Resource for Clinicians.  Baltimore: The Johns Hopkins University Press 1994: 122-124
    Suche in Google Scholar
  • 69 Ebling L. Congenital malformations in mice after gonadotropin-induced ovulation.  Proc Soc Exp Biol Med . 1975;  149 376-379
    PubMedSuche in Google Scholar
  • 70 Yang W H, Chang M C. Interruption of pregnancy in the rat and hamster by administration of PMS or HCG.  Endocrinology . 1968;  83 217-224
    PubMedSuche in Google Scholar
  • 71 Moor R M, Rowson L E, Hay M F, Caldwell B V. The effect of exogenous gonadotropins on the conceptus and corpus luteum in pregnant sheep.  J Endocrinol . 1969;  44 495-499
    PubMedSuche in Google Scholar