Semin Reprod Med 2001; 19(1): 007-018
DOI: 10.1055/s-2001-13906
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

An Overview of the Past, Present, and Future of Nongonadal LH/hCG Actions in Reproductive Biology and Medicine

Ch. V. Rao
  • Department of Obstetrics and Gynecology, Division of Basic Science Research, University of Louisville Health Sciences Center, Louisville, Kentucky
Further Information

Publication History

Publication Date:
31 December 2001 (online)

ABSTRACT

Even though there were hints, it was not until 1986 that a number of laboratories worldwide began to demonstrate unequivocally the presence and functions of luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors in various female and male nongonadal tissues. There was no species specificity but there was tissue specificity in the nongonadal LH/hCG receptor distribution. Nongonadal receptor levels were lower but they were regulated and processed and used signaling mechanisms similarly to gonadal receptors. Although still greater understanding is needed, gains made in the last decade demonstrate that nongonadal actions of LH/hCG are physiologically important and may have relevance to better understanding several diseases and their treatment. A recently developed LH receptor knockout model has begun to reaffirm and extend the importance of nongonadal LH signaling in the body.

REFERENCES

  • 1 Pierce J G, Parsons T F. Glycoprotein hormones: structure and function.  Annu Rev Biochem . 1981;  50 466-495
  • 2 Lapthorn A J, Harris D C, Littlejohn A. Crystal structure of human chorionic gonadotropin.  Nature . 1994;  369 455-461
  • 3 Lei Z M, Rao C V. Endocrinology of trophoblast tissue. In: Becker K, Rebar R, eds. Principle and Practice of Endocrinology and Metabolism, 3rd ed. In press. Philadelphia: Lippincott Williams & Wilkins
  • 4 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
  • 5 Loosfelt H, Misrahi M, Atger M. Cloning and sequencing of porcine LH/hCG receptor cDNA: variants lacking transmembrane domain.  Science . 1989;  245 525-528
  • 6 Rao C V. Differential properties of human chorionic gonadotropin and human luteinizing hormone binding to plasma membranes of bovine corpora lutea.  Acta Endocrinol . 1979;  90 696-710
  • 7 Rao C V, Saxena B B, Gandy H M. The subcellular distribution of human chorionic gonadotropin in rat corpus luteum. In: Saxena BB, Beling CG, Gandy HM, eds. Gonadotropins New York: John Wiley & Sons 1972: 261-268
  • 8 Coulson P, Liu T-C, Morris P, Gorski J. Interaction of LH with the ovary. In: Saxena BB, Beling CG, Gandy H, eds. Gonadotropins New York: John Wiley & Sons 1972: 227-247
  • 8a Rajaniemi H. Distribution of pituitary gonadotropins in experimental animal and binding to target issues. Doctoral thesis, University of Tusku, Finland, 1971
  • 9 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
  • 9a Abdallah M, Lei Z M, Li X. Human fetal organs contain hCG/LH receptors.  J Soc Gynecol Invest. 2001;  8(suppl) Abstract 200
  • 10 You S, Kim H, Hsu C-C, El Halawani E M, Foster D N. Three different turkey luteinizing hormone receptor (tLH-R) isoforms: I. Characterization of alternatively spliced tLH-R isoforms and their regulated expression in diverse tissues.  Biol Reprod . 2000;  62 108-116
  • 11 Lei Z M, Toth P, Rao C V, Pridham D. Novel co-expression 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
  • 12 Han S W, Lei Z M, Rao C V. Up-regulation of cyclooxygenase-2 gene expression by chorionic gonadotropin in mucosal cells from human fallopian tubes.  Endocrinology . 1996;  137 2929-2937
  • 13 Sun T, Lei Z M, Rao C V. A novel regulation of the oviductal glycoprotein gene expression by luteinizing hormone in bovine tubal epithelial cells.  Mol Cell Endocrinol . 1997;  131 97-108
  • 14 Gawronska B, Paukku T, Huhtaniemi I, Wasowicz G, Ziecik A J. Oestrogen-dependent expression of LH/hCG receptors in pig fallopian tube and their role in relaxation of the oviduct.  J Reprod Fertil . 1999;  115 293-301
  • 15 Mishra S, Lei Z M, Rao C V. A novel role for luteinizing hormone in promoting the development of early bovine embryos into blastocysts through its actions on oviductal epithelial cells.  Biol Reprod. 1999;  60(suppl) abstract 185
  • 16 Mishra S, Lei Z M, Rao C V. Novel effect of luteinizing hormone and human chorionic gonadotropin on the release of sperm bound to oviductal epithelial cells.  J Soc Gynecol Invest . 1999;  6(suppl 1) abstract 45
  • 17 Jensen J D, Odell W D. Identification of LH/hCG receptors in rabbit uterus (42775).  Proc Soc Exp Biol Med . 1988;  189 28-30
  • 18 Bonnamy P J, Benhaim A, Leymarie P. Human chorionic gonadotropin affects tissue levels of progesterone and cyclic adenosine 3'-5'-monophosphate in the metestrus rat uterus in vitro.  Biol Reprod . 1989;  40 511-516
  • 19 Reshef E, Lei Z M, Rao C V, Pridham D D, Chegini N, Luborsky J L. The presence of gonadotropin receptors in nonpregnant human uterus, human placenta, fetal membranes and decidua.  J Clin Endocrinol Metab . 1990;  70 421-430
  • 20 Bonnamy P J, Benhaim A, Leymarie P. Estrous cycle-related changes of high affinity luteinizing hormone/human chorionic gonadotropin binding sites in the rat uterus.  Endocrinology . 1990;  126 1264-1269
  • 21 Sawitzke A L, Odell W D. Uterine binding sites for LH/hCG can be modulated by hormonal status in rabbits and rats.  Acta Endocrinol (Copenh) . 1991;  124 322-330
  • 22 Flowers B, Ziecik A J, Caruolo E V. Effects of human chorionic gonadotropin on contractile activity of steroid-primed pig myometrium in vitro.  J Reprod Fertil . 1991;  92 425-432
  • 23 Lei Z M, Reshef E, Rao C V. The expression of human chorionic gonadotropin/luteinizing hormone receptors in human endometrial blood vessels.  J Clin Endocrinol Metab . 1992;  75 651-659
  • 24 Sen S, Bhattacharya S. Binding of radiolabeled luteinizing hormone to intact and ovariectomized rat uterus.  Indian J Exp Biol . 1992;  30 972-976
  • 25 Ziecik A J, Jedlinska M, Rzucidlo S J. Effect of estradiol and progesterone on myometrial LH/hCG receptors in pigs.  Acta Endocrinol . 1992;  127 185-188
  • 26 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
  • 27 Bonnamy P J, Benhaim A, Leymarie P. Uterine luteinizing hormone/human chorionic gonadotropin-binding sites in the early pregnant rat uterus: evidence for total occupancy in the peri-implantation period.  Endocrinology . 1993;  132 1240-1246
  • 28 Bhattacharya S, Bannerjee J, Sen S, Manna P R. Human chorionic gonadotropin binding sites in the human endometrium.  Acta Endocrinol . 1993;  129 15-19
  • 29 Tang B, Gurpide E. Direct effect of gonadotropins on decidualization of human endometrial stromal cells.  J Steroid Biochem Mol Biol . 1993;  47 115-121
  • 30 Ziecik A J, Gajewski Z, Jedruch J, Barcikowski B. Effect of human chorionic gonadotropin on myometrial electrical activity in the pig.  Anim Reprod Sci . 1993;  31 131-139
  • 31 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
  • 32 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
  • 33 Mukherjee D, Manna P R, Bhattacharya S. Functional relevance of luteinizing hormone receptor in mouse uterus.  Eur J Endocrinol . 1994;  131 103-108
  • 34 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
  • 35 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
  • 36 Bernardini L, Moretti-Rojas I, Brush M, Rojas 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
  • 37 Freidman S, Gurevich M, Shemesh M. Bovine cyclic endometrium contains high-affinity luteinizing hormone/ human chorion gonadotropin binding sites.  Biol Reprod . 1995;  52 1020-1026
  • 38 Kisielewska J, Flint A PF, Ziecik A J. Phospholipase C and adenylate cyclase signaling systems in the action of hCG on porcine myometrial smooth muscle cells.  J Endocrinol . 1996;  148 175-180
  • 39 Han S W, Lei Z M, Rao C V. Homologous down-regulation of luteinizing hormone/chorionic gonadotropin receptors by increasing the degradation of receptor transcripts in human uterine endometrial stromal cells.  Biol Reprod . 1997;  57 158-164
  • 40 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
  • 41 Chatterjee A, Jana N R, Bhattacharya S. Stimulation of cyclic AMP, 17β-oestradiol and protein synthesis by human chorionic gonadotrophin in human endometrial cells.  Hum Reprod . 1997;  12 1903-1908
  • 42 Shemesh M, Gurevich M, Mizrachi D. Expression of functional luteinizing hormone (LH) receptor and its messenger ribonucleic acid in bovine uterine veins: LH induction of cyclooxygenase and augmentation of prostaglandin production in bovine uterine veins.  Endocrinology . 1997;  138 4844-4851
  • 43 Toppozada M K. Does hCG have a direct effect on the human myometrium?.  Program of the 16th World Congress on Fertility and Sterility and the 54th Annual Meeting of the SRM 1998;70:Abstract 184 
  • 44 Han S W, Lei Z M, Rao C V. Treatment of human endometrial stromal cells with chorionic gonadotropin induces their morphological and functional differentiation into decidua.  Mol Cell Endocrinol . 1999;  147 7-16
  • 45 Zhou X L, Lei Z M, Rao C V. Treatment of human endometrial gland epithelial cells with chorionic gonadotropin/luteinizing hormone increases the expression of cyclooxygenase-2 gene.  J Clin Endocrinol Metab . 1999;  84 3364-3377
  • 46 Derecka K, Zhang F P, Ziecik A J, Huhtaniemi I. Ontogeny of LH receptor gene expression in the pig reproductive tract.  J Reprod Fertil . 1999;  115 365-372
  • 47 Munir I, Fukunaga K, Miyazaki K, Okamura H, Miyamoto E. Mitogen-activated protein kinase activation and regulation of cyclooxygenase 2 expression by platelet-activating factor and hCG in human endometrial adenocarcinoma cell line HEC-1B.  J Reprod Fertil . 1999;  117 49-59
  • 48 Fazleabas A T, Donnelly K M, Srinivasan S, Fortman J D, Miller J B. Modulation of the baboon (Papio anubis) uterine endometrium by chorionic gonadotropin during the period of uterine receptivity.  Proc Natl Acad Sci U S A . 1999;  96 2543-2548
  • 49 Kurtzman J T, Spinnato J T, 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
  • 50 Srisuparp S, Strakova Z, Luborsky J, Fazleabas A T. Signaling pathways activated by chorionic gonadotropin (CG) in the primate endometrium.  Biol Reprod . 2000;  62(suppl 1) abstract 33
  • 51 Peng X, Kim J J, Fazleabas A T. Apoptosis and differentiation in baboon stromal cells: a role for chorionic gonadotropin (CG)?.  Biol Reprod . 2000;  62(suppl 1) abstract 510
  • 52 Selam B, Kayisli U A, Arici A. Human chorionic gonadotropin up-regulates fas ligand expression in endometrial stromal cells: a mechanism for an immuno-privileged trophoblastic invasion.  J Soc Gynecol Invest . 2000;  7(suppl 1) abstract 594
  • 53 Uzumcu M, Coskun S, Jaroudi K, Hollanders J MG. Effect of human chorionic gonadotropin on cytokine production from human endometrial cells in vitro.  Am J Reprod Immunol . 2000;  40 83-88
  • 54 d'Hauterive S P, Hazee-Hagelstein M-T, Hazout A, Geenen V. The materno-fetal interface: embryonic factors (hCG, IGF-2) regulate the expression of endometrial cytokines, and TGFβ-related peptides contribute to maternal tolerance of the fetal graft. Program of the Endocrine Society Annual Meeting, 2000, abstract 822
  • 55 Horiuchi A, Nikaido T, Yoshizawa T. Human chorionic gonadotropin promotes proliferation of uterine leiomyomal cells greater than that of myometrial smooth muscle cells in vitro.  Mol Hum Reprod . 2000;  6 523-528
  • 56 Kurtzman J, Jones E, Goldsmith L J. Inhibition of preterm delivery by human chorionic gonadotropin is associated with down-regulation of myometrial gap junctions.  Am J Obstet Gynecol. 2000;  182 abstract 668
  • 57 Phillips R J, Robson S C, Europe-Finner G N. Regulation of gas gene expression in human myometrial cells by chorionic gonadotropin: a cAMP-mediated process.  J Soc Gynecol Invest . 2000;  7(suppl 1) abstract 668
  • 58 Fanchin R, Peltier E, Frydman R, deZiegler D. Human chorionic gonadotropin: does it affect human endometrial morphology in vivo.  Semin Reprod Med . 2001;  19 31-36
  • 59 Licht, P, Russu V, Wildt L. On the role of human chorionic gonadotropin (hCG) in the embryo-endometrial microenvironment: implications for differentiation and implantation.  Semin Reprod Med . 2001;  19 37-48
  • 60 Zygmunt M, Herr F, Keller-Schoenwetter S. Characterization of human chorionic gonadotropin as an angiogenic factor.  In review, 2001.
  • 61 Mizrachi D, Shemesh M. Expression of functional luteinizing hormone receptor and its messenger ribonucleic acid in bovine cervix: luteinizing hormone augmentation of intracellular cyclic AMP, phosphate inositol and cyclooxygenase.  Mol Cell Endocrinol . 1999;  157 191-200
  • 62 Lin P C, Li X, Lei Z M, Rao C V. Human cervix LH/hCG receptors are functional. Submitted to the Endocrine Society Annual Meeting, 2001
  • 63 Shi Q J, Lei Z M, Rao C V, Lin J. Novel role of human chorionic gonadotropin in differentiation of human cytotrophoblasts.  Endocrinology . 1993;  132 1387-1395
  • 64 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
  • 65 Licht P, Cao H, Zuo J. Lack of self-regulation of human chorionic gonadotropin biosynthesis in human choriocarcinoma cells.  J Clin Endocrinol Metab . 1994;  78 1188-1194
  • 66 Tao Y-X, Lei Z M, Hofmann G E, Rao C V. Human intermediate trophoblasts express chorionic gonadotropin/luteinizing hormone receptor gene.  Biol Reprod . 1995;  53 899-904
  • 67 Hu Y L, Lei Z M, Rao C V. Cis-acting elements and trans-acting proteins in the transcription of chorionic gonadotropin/ luteinizing hormone receptor gene in choriocarcinoma cells and placenta.  Endocrinology . 1996;  137 3897-3905
  • 68 Zygmunt M, Hahn D, Munstedt K, Bischof P, Lang U. Invasion of cytotrophoblastic JEG-3 cells is stimulated by hCG.  Placenta . 1998;  19 587-593
  • 69 Jauniaux E, Bao S, Eblen A. Human chorionic gonadotropin concentration and receptor gene expression in placental tissue from trisomy 18 and 21.  Mol Human Reprod . 2000;  6 5-10
  • 70 Lei Z M, Rao C V. The immunoprotective role of human chorionic gonadotropin at fetal-maternal interface.  J Soc Gynecol Invest . 2000;  7(suppl 1) abstract 504
  • 71 Toth P, Li X, Lei Z M, Rao C V. Expression of human chorionic gonadotropin (hCG)/luteinizing hormone (LH) receptors and regulation of cyclooxygenase-1 gene by exogenous hCG in human fetal membranes.  J Clin Endocrinol Metab . 1996;  81 1283-1288
  • 72 Rao C V, Li X, Toth P, Lei Z M, Cook V D. Novel expression of functional human chorionic gonadotropin/luteinizing hormone receptor gene in human umbilical cords.  J Clin Endocrinol Metab . 1993;  77 1706-1714
  • 73 Wasowicz G, Derecka K, Pelliniemi L, Boboszynska T, Gawronska B, Ziecik A J. Evidence for the presence of luteinizing hormone-chorionic gonadotropin receptors in the pig umbilical cord.  J Reprod Fertil . 1999;  117 1-9
  • 74 Lin J, Lojun S, Lei Z M, Wu W X, Peiper S C, Rao C V. Lymphocytes from pregnant women express human chorionic gonadotropin/luteinizing hormone receptor gene.  Mol Cell Endocrinol . 1995;  111 R13-R17
  • 75 Zhang Y M, Lei Z M, Rao C V. Human macrophages contain luteinizing hormone and chorionic gonadotropin receptors.  J Soc Gynecol Invest . 1998;  5(suppl 1) abstract 212
  • 76 Zhang Y M, Lei Z M, Rao C V. Functional importance of human monocyte luteinizing hormone and chorionic gonadotrophin receptors.  J Soc Gynecol Invest . 1999;  6(suppl 1) abstract 46
  • 77 Tao Y-X, Heit M, Lei Z M, Rao C V. The urinary bladder of a women is a novel site of luteinizing hormone/human chorionic gonadotropin receptor gene expression.  Am J Obstet Gynecol . 1998;  179 1026-1031
  • 78 Zhou X L, Lei Z M, Rao C V. Functional importance of urinary bladder luteinizing hormone/human chorionic gonadotropin receptors.  J Soc Gynecol Invest . 1999;  6(suppl 1) abstract 731
  • 79 Pabon J E, Bird J S, Li X. Human skin contains luteinizing hormone/chorionic gonadotropin receptors.  J Clin Endocrinol Metab . 1996;  81 2738-2741
  • 80 Bird J, Li X, Lei Z M, Sanfilippo J, Yussman M A, Rao C V. Luteinizing hormone and human chorionic gonadotropin decrease type 2 5-α reductase and androgen receptor protein levels in women's skin.  J Clin Endocrinol Metab . 1998;  83 1776-1782
  • 81 Li X, Lei Z M, Rao C V. Human bone contains functional luteinizing hormone/human chorionic gonadotropin receptors. Program of the Endocrine Society Annual Meeting, 2000, abstract 259
  • 82 Pabon J E, Li X, Lei Z M, Sanfilippo J, Yussman M A, Rao C V. Novel presence of human luteinizing hormone/chorionic gonadotropin receptors in the human adrenal glands.  J Clin Endocrinol Metab . 1996;  81 2397-2400
  • 83 Zhou X L, Lei Z M, Rao C V. Human adrenal cortical H295R cells contain functional luteinizing hormone/chorionic gonadotropin receptors: a potential explanation for increased androgen levels in chorionic anovulatory women.  J Soc Gynecol Invest . 1998;  5(suppl 1) abstract 45
  • 84 Lei Z M, Rao C V, Kornyei J L, Licht P, Hiatt E S. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain.  Endocrinology . 1993;  132 2262-2270
  • 85 Lei Z M, Rao C V. Novel presence of luteinizing hormone/ human chorionic gonadotropin (hCG) receptors and the down-regulating action of hCG on gonadotropin releasing hormone gene expression in immortalized hypothalamic GT1-7 neurons.  Mol Endocrinol . 1994;  8 1111-1121
  • 86 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 associated behaviors in cycling female rats.  Brain Res . 1994;  654 181-190
  • 87 Lukacs H, Hiatt E S, Lei Z M, Rao C V. Peripheral and intracerebroventricular administration of human chorionic gonadotropin alters several hippocampus associated behaviors in cycling female rats.  Horm Behav . 1995;  29 42-58
  • 88 Lei Z M, Rao C V. Signaling and trans-acting factors in the transcriptional inhibition of gonadotropin releasing hormone gene by human chorionic gonadotropin in immortalized hypothalamic GT1-7 neurons.  Mol Cell Endocrinol . 1995;  109 151-157
  • 89 Huang Z H, Lei Z M, Rao C V. Immortalized anterior pituitary αT3 gonadotropes contain functional luteinizing hormone/human chorionic gonadotropin receptors.  Mol Cell Endocrinol . 1995;  114 217-222
  • 90 Li X, Lei Z M, Rao C V. Human chorionic gonadotropin down-regulates the expression of gonadotropin releasing hormone receptor gene in GT1-7 neurons.  Endocrinology . 1996;  137 899-904
  • 91 Mores N, Krsmanovic L, Catt K J. Activation of LH receptors expressed in GnRH neurons stimulates cyclic AMP production and inhibits pulsatile neuropeptide release.  Endocrinology . 1996;  137 5731-5734
  • 92 Lei Z M, Rao C V. Cis-acting elements and trans-acting proteins in the transcriptional inhibition of gonadotropin releasing hormone gene by human chorionic gonadotropin in immortalized hypothalamic GT1-7 neurons.  J Biol Chem . 1997;  272 14365-14371
  • 93 Huang Z-H, Lei Z M, Rao C V. Novel independent and synergistic regulation of gonadotropin-α-subunit gene by luteinizing hormone/human chorionic gonadotropin and gonadotropin releasing hormone in the αT3-1 gonadotropin cells.  Mol Cell Endocrinol . 1997;  130 23-31
  • 94 Hu Y L, Lei Z M, Rao C V. Analysis of the promoter of luteinizing hormone/human chorionic gonadotropin receptor gene in neuroendocrine cells.  Life Sci . 1998;  63 2157-2165
  • 95 Skipor J, Bao S, Grzegorzewski W, Wsowska B, Krzymowski T, Rao C V. The inhibitory effect of hCG on counter current transfer of GnRH and the presence of LH/hCG receptors in the perihypophysial cavernous sinus-carotid rete vascular complex of ewes.  Theriogenology . 1999;  51 899-910
  • 96 Zhang W, Lei Z M, Rao C V. Immortalized hippocampal neurons contain functional luteinizing hormone/human chorionic gonadotropin receptors.  Life Sci . 1999;  65 2081-2098
  • 97 Thompson D A, Othman M I, Lei Z M. Localization of the receptor for luteinizing hormone/chorionic gonadotropin in neural retina.  Life Sci . 1998;  63 1057-1064
  • 98 Tay L K, Russo J. Effect of human chorionic gonadotropin on 7,12-dimethylbenz[a] anthracene-induced DNA binding and repair synthesis by rat mammary epithelial cells.  Chem Biol Interact . 1985;  55 13-21
  • 99 Russo I H, Koszalka M, Russo J. Effect of human chorionic gonadotropin on mammary gland differentiation and carcinogenesis.  Carcinogenesis . 1990;  11 1849-1855
  • 100 Alvarado M V, Russo J, Russo I H. Immunolocalization of inhibin in the mammary gland of rats treated with hCG.  J Histochem Cytochem . 1993;  41 29-34
  • 101 Alvarado M V, Alvarado N E, Russo J, Russo I H. Human chorionic gonadotropin inhibits proliferation and induces expression of inhibin in human breast epithelial cells in vitro.  In Vitro Cell Dev Biol . 1994;  30A 4-8
  • 102 Alvarado M V, Ho T Y, Russo J, Russo I H. Human chorionic gonadotropin regulates the synthesis of inhibin in the ovary and mammary gland of rat.  Endocrine . 1994;  2 1107-1114
  • 103 Ho T Y, Russo J, Russo I H. Polypeptide pattern of human breast epithelial cells following human chorionic gonadotropin (hCG) treatment.  Electrophoresis . 1994;  15 746-750
  • 104 Tao Y-X, Lei Z M, Rao C V. The presence of luteinizing hormone/human chorionic gonadotropin receptors in lactating rat mammary glands.  Life Sci . 1997;  60 1297-1303
  • 105 Lojun S, Bao S, Lin J, Lei Z M, Rao C V. The presence of functional luteinizing hormone/chorionic gonadotropin (hCG) receptors in human breast cell lines: implications supporting the premise that hCG protects women against breast cancer.  Biol Reprod . 1997;  57 1202-1210
  • 106 Meduri G, Charnaux N, Loosfelt H. Luteinizing hormone/human chorionic gonadotropin receptors in breast cancer.  Cancer Res . 1997;  57 857-864
  • 107 Srivastava P, Russo J, Russo I H. Chorionic gonadotropin inhibits rat mammary carcinogenesis through activation of programmed cell death.  Carcinogenesis . 1997;  18 1799-1808
  • 108 Srivastava P, Russo J, Mgbonyebi O P, Russo I H. Growth inhibition and activation of apoptotic gene expression by human chorionic gonadotropin in human breast epithelial cells.  Anticancer Res . 1998;  18 4003-4010
  • 109 Huynh H. In vivo regulation of the insulin-like growth factor system of mitogens by human chorionic gonadotropin.  Int J Oncol . 1998;  13 571-575
  • 110 Srivastava P, Silva I D, Russo J, Mgbonyebi O P, Russo I H. Identification of new genes differentially expressed in breast carcinoma cells treated with human gonadotropin on DMBA-induced mammary carcinogenesis.  Br J Cancer . 1998;  62 243-247
  • 111 Li X, Lei Z M, Rao C V. The actions of human chorionic gonadotropin in MCF-7 cells support the premise that it may protect women against breast cancer. Program of the Endocrine Society Annual Meeting, 1999, abstract P3-195
  • 112 Hu Y L, Lei Z M, Huang Z H, Rao C V. Determinants of transcription of the chorionic gonadotropin/luteinizing hormone receptor gene in human breast cells.  Breast J . 1999;  5 186-193
  • 113 Rao C V. Does full-term pregnancy at a young age protect women against breast cancer through hCG?.  Obstet Gynecol . 2000;  96 783-786
  • 114 Ghinea N, Hai M TV, Groyer-Picard M T, Milgrom E. How protein hormones reach their target cells: receptor mediated transcytosis of hCG through endothelial cells.  J Cell Biol . 1994;  125 87-97
  • 115 Hill J B, Jiminez A L, Passmore J C, Rao C V. Effect of human chorionic gonadotropin on reproductive organ blood flow in cycling rats.  Proc Soc Exp Biol Med . 1996;  211 94-99
  • 116 Hill J B, Alsip N L, Rao C V, Asher E F. Human chorionic gonadotropin directly and indirectly alters the uterine arteriolar diameters in cycling rats.  Am J Obstet Gynecol . 1997;  176 150-157
  • 117 Toth P. Clinical data supporting importance of vascular LH/hCG receptors of uterine blood vessels.  Semin Reprod Med . 2001;  19 55-62
  • 118 Rao C V, Alsip N L. Use of the rat model to study hCG/LH effects on uterine blood flow.  Semin Reprod Med . 2001;  19 75-86
  • 119 Tao Y X, Lei Z M, Woodworth S H, Rao C V. Novel expression of luteinizing hormone/chorionic gonadotropin receptor gene in rat prostate.  Mol Cell Endocrinol . 1995;  111 R9-R12
  • 120 Reiter E, McNamara M, Closset J, Hennen G. Expression and functionality of luteinizing hormone/chorionic gonadotropin receptor in the rat prostate.  Endocrinology . 1995;  136 917-923
  • 121 Reiter E, Poncin J, Hennuy B. Luteinizing hormone increases the abundance of various transcripts, independently of the androgens, in the rat prostate.  Biochem Biophys Res Commun . 1997;  233 108-112
  • 122 Bao S, Lei Z M, Rao C V. The presence of functional luteinizing hormone/chorionic gonadotropin receptors in human prostate cell lines. Program of the Endocrine Society Annual Meeting, 1997, abstract P3-403
  • 123 Tao Y X, Bao S, Ackermann D M, Lei Z M, Rao C V. Expression of luteinizing hormone/human chorionic gonadotropin receptor gene in benign prostatic hyperplasia and in prostate carcinoma in humans.  Biol Reprod . 1997;  56 67-72
  • 124 Dirnhofer S, Berger C, Hermann M, Steiner G, Maderbacher S, Berger P. Coexpression of gonadotrophic hormones and their corresponding FSH and LH/CG receptors in the human prostate.  Prostate . 1998;  35 212-220
  • 125 Lei Z M, Rao C V. Direct Luteinizing Hormone Regulation of the Male Reproductive Tract. In press. Amsterdam: Elsevier Science
  • 126 Tao Y X, Lei Z M, Rao C V. Novel expression of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor gene in rat epididymis.  Biol Reprod . 1995;  52(suppl 1) abstract 338
  • 127 Tao Y X, Lei Z M, Rao C V. Human epididymis contains luteinizing hormone/chorionic gonadotropin receptors. Program of the 10th International Congress of Endocrinology, 1996, abstract OR21-2
  • 128 Zhou H M, Zhang T, Liu Y X. Rat epididymis expresses luteinizing hormone receptor (LHR).  Chin Sci Bull . 1996;  41 1608-1610
  • 129 Zhang T, Guo C X, Hu Z Y, Liu Y X. Localization of plasminogen activator and inhibitor, LH and androgen receptors and inhibin subunits in monkey epididymis.  Mol Hum Reprod . 1997;  3 945-952
  • 130 Tao Y X, Lei Z M, Rao C V. Seminal vesicles are novel sites of luteinizing hormone/human chorionic gonadotropin-receptor gene expression.  J Androl . 1998;  19 343-347
  • 131 Eblen A, Bao S, Lei Z M, Nakajuma S T, Rao C V. The presence of luteinizing hormone chorionic gonadotropin receptors in human sperm.  In press.  J Clin Endocrinol Metab. 2001; 
  • 132 Han S W, Lei Z M, Rao C V. Hormonal regulation of luteinizing hormone/human chorionic gonadotropin receptor mRNA levels in human fallopian tube epithelial cells.  Biol Reprod . 1998;  58(suppl 1) abstract 406
  • 133 Cao H, Lei Z M, Rao C V. Consequences of antisense human chorionic gonadotropin- subunit cDNA expression in human choriocarcinoma JAR cells.  J Mol Endocrinol . 1995;  14 337-347
  • 134 Lei Z M, Taylor D D, Gercel-Taylor C, Rao C V. Human chorionic gonadotropin promotes tumorigenesis of choriocarcinoma JAR cells.  Trophoblast Res . 1999;  13 147-159
  • 135 Patil A A, Nagaraj M P. The effect of hCG on functional recovery of spinal cord sectioned rats.  Acta Neurochir (Wien) . 1983;  69 205-218
  • 136 Patil A A, Filmore K, Hill D. The effect of hCG on restoration of physiological continuity of the spinal cord: a preliminary report.  Int Surg . 1990;  75 54-57
  • 137 Gorby G L, Clemens C M, Barley L R, McGee Z A. Effect of human chorionic gonadotropin (hCG) on Neisseria gonorrhoeae invasion of and IgA secretion by human fallopian tube mucosa.  Microb Pathog . 1991;  10 373-384
  • 138 Spence J M, Chen JC-R, Clark V L. A proposed role for the lutropin receptor in contact-inducible gonococcal invasion of hec1B cells.  Infect Immun . 1997;  65 3736-3742
  • 139 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
  • 140 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
  • 141 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
  • 142 Singh M, Zuo J, Li X. The decreased expression of functional human chorionic gonadotropin/luteinizing hormone receptor gene in human uterine leiomyomas.  Biol Reprod . 1995;  53 591-597
  • 143 Konishi I, Koshiyama M, Mandai M. Increased expression of LH/hCG receptors in endometrial hyperplasia and carcinoma in anovulatory women.  Gynecol Oncol . 1997;  65 273-280
  • 144 Danikas D, Goudas V T, Rao C V, Brief D K. Luteinizing hormone receptor expression in leiomyomatosis peritonealis disseminata.  Obstet Gynecol . 2000;  95 1009-1011
  • 145 Bugalho M J, Li X, Rao C V, Soares J, Sobrinho L G. Presence of a GSα mutation in an adrenal tumor expressing LH/hCG receptors and clinically associated with Cushing's syndrome.  Gynecol Endocrinol . 1999;  14 50-54
  • 146 Wv L, Carlson H E, Kane P, Li X, Lei Z M, Rao C V. Pregnancy-associated Cushing's syndrome secondary to an hCG/ LH receptor-positive adrenal carcinoma.  In review, 2001 
  • 147 De S K, Wohlenberg C R, Marinos N J, Doodnauth D, Bryant J L, Notkins A L. Human chorionic gonadotropin hormone prevents wasting syndrome and death in HIV-1 transgenic mice.  J Clin Invest . 1997;  99 1484-1491
  • 148 Shapira A, Bao S, Lei Z M, Notkins A L, De S K, Rao C V. Treatment of homozygous HIV-1 transgenic mouse pups with human chorionic gonadotropin (hCG) up-regulates the skin hCG/luteinizing hormone receptor levels. Program of The Endocrine Society Annual Meeting, 1998, abstract P2-149
  • 149 Huang Y, Bove B, Wu Y, Russo I H, Yang X, Russo J. Microsatellite instability during the immortalization and transformation of human breast epithelial cells in vitro.  Mol Carcinog . 1999;  24 118-127
  • 150 Leuschner C, Hansel W. A novel approach in prostate cancer therapy: lytic peptides conjugated to luteinizing hormone kill prostate cancer cells.  Biol Reprod . 1999;  60(suppl 1) abstract 510
  • 151 Mishra S, Lin P C, Lei Z M, Carrillo A J, Rao C V. Evidence for the presence of human chorionic gonadotropin/luteinizing hormone receptors in human oocytes and early embryos.  J Soc Gynecol Invest . 2000;  7(suppl 1) abstract 576
  • 152 Simón C, Mercader A, Garcia-Velasco J. Coculture of human embryos with autologous human endometrial epithelial cells in patients with implantation failure.  J Clin Endocrin Metab . 1999;  84 2638-2646
  • 153 Rao S C, Rao C V, Magnuson D SK. Human chorionic gonadotropin/luteinizing hormone receptor expression in the adult rodent.  In review, 2001 
  • 154 AL-Hader A A, Lei Z M, Rao C V. Novel expression of functional luteinizing hormone/ chorionic gonadotropin receptors in cultured glial cells from neonatal rat brains.  Biol Reprod . 1997;  56 501-507
  • 155 AL-Hader A A, Lei Z M, Rao C V. Neurons from fetal rat brains contain functional luteinizing hormone/chorionic gonadotropin receptors.  Biol Reprod . 1997;  56 1071-1076
  • 156 Griffiths S J, Adams D J, Talbot S J. Ribonuclease inhibits Kaposi's sarcoma.  Nature . 1997;  390 568
  • 157 Lee-Huang S, Huang P L, Sun Y. Lysozyme and RNase as anti-HIV components in β-core preparations of human chorionic gonadotropin.  Proc Natl Acad Sci U S A . 1999;  96 2678-2681
  • 158 Lunardi-Iskandar Y, Bryant J L, Blattner W A. Effects of a urinary factor from women in early pregnancy on HIV-1, SIV and associated disease.  Nat Med . 1998;  4 428-434
  • 159 Harris P J. Human chorionic gonadotropin hormone is antiviral.  Med Hypotheses . 1996;  47 71-72
  • 160 Bourinbaiar A S, Nagonny R. Effect of human chorionic gonadotropin (hCG) on reverse transcriptase activity in HIV-1 infected lymphocytes and monocytes.  FEMS Microbiol Lett . 1992;  96 27-30
  • 161 Bourinbaiar A S, Nagonny R, Tan X. Pregnancy hormones, estrogen and progesterone, prevent HIV-1 synthesis in monocytes but not in lymphocytes.  FEBS Lett . 1992;  302 206-208
  • 162 Bourinbaiar A S, Nagorny R. Inhibitory effects of human chorionic gonadotropin (hCG) on HIV-1 transmission from lymphocytes to trophoblasts.  FEBS Lett . 1992;  309 82-84
  • 163 Bourinbaiar A S, Lee-Huang S. Anti-HIV effect of beta subunit of human chorionic gonadotropin (βhCG) in vitro.  Immunol Lett . 1995;  44 13-18
  • 164 Manna S K, Mukhopadhyay A, Aggarwal B B. Human chorionic gonadotropin suppresses activation of nuclear transcription factor kβ and activator protein-1 induced by tumor necrosis factor.  J Biol Chem . 1999;  275 13307-13314
  • 165 Rao C V. A paradigm shift on the targets of luteinizing hormone/human chorionic gonadotropin actions in the body.  J Bellevue Obstet Gynecol Soc . 1999;  15 26-32
  • 166 Lei Z M, Mishra S, Zou W. Targeted disruption of luteinizing hormone/human chorionic gonadotropin receptor gene.  Mol Endocrinol . 2001;  15 184-200
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