Genomes and Genes
Summary: Those protein complexes or molecular sites on the surfaces and cytoplasm of gonadal cells that bind luteinizing or chorionic gonadotropic hormones and thereby cause the gonadal cells to synthesize and secrete sex steroids. The hormone-receptor complex is internalized from the plasma membrane and initiates steroid synthesis.
- Liu T, Wimalasena J, Bowen R, Atwood C. Luteinizing hormone receptor mediates neuronal pregnenolone production via up-regulation of steroidogenic acute regulatory protein expression. J Neurochem. 2007;100:1329-39 pubmed
- Madhra M, Gay E, Fraser H, Duncan W. Alternative splicing of the human luteal LH receptor during luteolysis and maternal recognition of pregnancy. Mol Hum Reprod. 2004;10:599-603 pubmed..We hypothesized that alternatively spliced LH receptors are involved in luteolysis and luteal rescue with hCG in women...
- Menon K, Munshi U, Clouser C, Nair A. Regulation of luteinizing hormone/human chorionic gonadotropin receptor expression: a perspective. Biol Reprod. 2004;70:861-6 pubmed..We also propose a model to explain the loss of steady-state LH/hCG receptor mRNA levels during receptor down-regulation. ..
- Licht P, Russu V, Lehmeyer S, Wildt L. Molecular aspects of direct LH/hCG effects on human endometrium--lessons from intrauterine microdialysis in the human female in vivo. Reprod Biol. 2001;1:10-9 pubmed..In summary, intrauterine microdialysis is a novel tool for the clinical assessment of endometrial paracrinology in vivo. HCG appears to directly modulate endometrial differentiation and function in humans. ..
- Huhtaniemi I, Themmen A. Mutations in human gonadotropin and gonadotropin-receptor genes. Endocrine. 2005;26:207-17 pubmed
- Perrier d Hauterive S, Charlet Renard C, Berndt S, Dubois M, Munaut C, Goffin F, et al. Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium. Hum Reprod. 2004;19:2633-43 pubmed..Other growth factors present at the embryonic-endometrial interface are also involved in the control of LIF and IL-6 endometrial secretion. ..
- Powell B, Piersma D, Kevenaar M, van Staveren I, Themmen A, Iacopetta B, et al. Luteinizing hormone signaling and breast cancer: polymorphisms and age of onset. J Clin Endocrinol Metab. 2003;88:1653-7 pubmed..Our findings suggest that the LHR18insLQ gene polymorphism determines an earlier age of disease onset and is prognostic for poor outcome of breast cancer. ..
- Patsoula E, Loutradis D, Drakakis P, Michalas L, Bletsa R, Michalas S. Messenger RNA expression for the follicle-stimulating hormone receptor and luteinizing hormone receptor in human oocytes and preimplantation-stage embryos. Fertil Steril. 2003;79:1187-93 pubmedTo study the expression of the FSH and LH receptors in human oocytes and preimplantation embryos and their potential roles in early human development. Clinical and molecular studies. University hospital IVF center...
- Apaja P, Harju K, Aatsinki J, Petäjä Repo U, Rajaniemi H. Identification and structural characterization of the neuronal luteinizing hormone receptor associated with sensory systems. J Biol Chem. 2004;279:1899-906 pubmed..Taken together, these results indicate that the neuronal LHR is a functional protein, implicating a role in neuronal development and function, possibly by means of regulating synthesis of neurosteroids. ..
- LaPolt P, Leung K, Ishimaru R, Tafoya M, You hsin Chen J. Roles of cyclic GMP in modulating ovarian functions. Reprod Biomed Online. 2003;6:15-23 pubmed..This report will review these previous findings and present new data demonstrating the inhibitory influence of cGMP on cAMP-stimulated LH receptor expression in cultured granulosa cells. ..
- Bukovsky A, Indrapichate K, Fujiwara H, Cekanova M, Ayala M, Dominguez R, et al. Multiple luteinizing hormone receptor (LHR) protein variants, interspecies reactivity of anti-LHR mAb clone 3B5, subcellular localization of LHR in human placenta, pelvic floor and brain, and possible role for LHR in the development of abnormal pregn. Reprod Biol Endocrinol. 2003;1:46 pubmed
- Funaro A, Sapino A, Ferranti B, Horenstein A, Castellano I, Bagni B, et al. Functional, structural, and distribution analysis of the chorionic gonadotropin receptor using murine monoclonal antibodies. J Clin Endocrinol Metab. 2003;88:5537-46 pubmed..This observation suggests that the mAb recognizes an epitope that is included in the domain of the receptor involved in the interaction with the natural ligand. ..
- Licht P, Fluhr H, Neuwinger J, Wallwiener D, Wildt L. Is human chorionic gonadotropin directly involved in the regulation of human implantation?. Mol Cell Endocrinol. 2007;269:85-92 pubmed..Taken together there appear to be multiple direct effects of hCG on the endometrium that precede the classical endocrine role of the hormone. ..
- Kosaka K, Fujiwara H, Tatsumi K, Yoshioka S, Sato Y, Egawa H, et al. Human chorionic gonadotropin (HCG) activates monocytes to produce interleukin-8 via a different pathway from luteinizing hormone/HCG receptor system. J Clin Endocrinol Metab. 2002;87:5199-208 pubmed
- de Roux N, Milgrom E. Inherited disorders of GnRH and gonadotropin receptors. Mol Cell Endocrinol. 2001;179:83-7 pubmed..Mutations provoking only partial alterations of receptor functions are relatively more frequent, than those inducing complete receptor inactivity. They provide interesting insights into the physiology of GnRH and gonadotropin action. ..
- Gawronska B, Leuschner C, Enright F, Hansel W. Effects of a lytic peptide conjugated to beta HCG on ovarian cancer: studies in vitro and in vivo. Gynecol Oncol. 2002;85:45-52 pubmed..0 +/- 21.72%) animals (P < 0.05). Immunocytochemical studies revealed the expression of LH/hCG receptor protein in the OVCAR-3 cells and tumor tissues. Hecate-beta hCG is a putative candidate for treating ovarian cancer. ..
- Bukovsky A, Ayala M, Dominguez R, Keenan J, Wimalasena J, Elder R, et al. Changes of ovarian interstitial cell hormone receptors and behavior of resident mesenchymal cells in developing and adult rats with steroid-induced sterility. Steroids. 2002;67:277-89 pubmed
- Ascoli M, Fanelli F, Segaloff D. The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr Rev. 2002;23:141-74 pubmed..As such, a full understanding of the biology of the LHR is essential to the survival of our species. In this review we summarize our current knowledge of the structure, functions, and regulation of this important receptor. ..
- Shenker A. Activating mutations of the lutropin choriogonadotropin receptor in precocious puberty. Receptors Channels. 2002;8:3-18 pubmed..As with rhodopsin, conformational signaling appears to depend on the rearrangement of key electrostatic, hydrogen-bond, and hydrophobic interactions that normally serve to stabilize the inactive LHR conformation. ..
- Richter Unruh A, Martens J, Verhoef Post M, Wessels H, Kors W, Sinnecker G, et al. Leydig cell hypoplasia: cases with new mutations, new polymorphisms and cases without mutations in the luteinizing hormone receptor gene. Clin Endocrinol (Oxf). 2002;56:103-12 pubmed..Alternatively, the displayed phenotype may be the result of other genetic defects. Our work further underscores the importance of thorough clinical analysis of patients before molecular analysis of a particular gene is performed. ..
- Kumar R, Ijiri S, Trant J. Molecular biology of the channel catfish gonadotropin receptors: 2. Complementary DNA cloning, functional expression, and seasonal gene expression of the follicle-stimulating hormone receptor. Biol Reprod. 2001;65:710-7 pubmed..51%-59%) to salmon gonadotropin receptor I and the FSH receptors of higher vertebrates, and less identical to LH receptors and thyrotropin receptors (45%-49% and 46%-47%, respectively)...
- Eppig J, Wigglesworth K, Pendola F, Hirao Y. Murine oocytes suppress expression of luteinizing hormone receptor messenger ribonucleic acid by granulosa cells. Biol Reprod. 1997;56:976-84 pubmed..In these follicles, mural granulosa cells express LH receptors (LHR) and LHR mRNA, but expression of these molecules is low or undetectable in cumulus cells...
- Rao C, Lei Z. Consequences of targeted inactivation of LH receptors. Mol Cell Endocrinol. 2002;187:57-67 pubmed..The knockout of LH receptors had no effect on gonadal FSH receptors in both sexes, progesterone receptors in females and androgen receptors ..
- Stepien A, Ziecik A. Second messenger systems in the action of LH and oxytocin on porcine endometrial cells in vitro. Theriogenology. 2002;57:2217-27 pubmed..Our observations lead to the conclusion that both protein kinase A and C second messenger systems are involved in LH action and that oxytocin is able to stimulate adenylate cyclase activity in porcine endometrial cells. ..
- Ghinea N, Milgrom E. A new function for the LH/CG receptor: transcytosis of hormone across the endothelial barrier in target organs. Semin Reprod Med. 2001;19:97-101 pubmed..A new role for the LH/CG receptor as a transcytotic carrier of its ligands in endothelial cells is suggested. ..
- Patsoula E, Loutradis D, Drakakis P, Kallianidis K, Bletsa R, Michalas S. Expression of mRNA for the LH and FSH receptors in mouse oocytes and preimplantation embryos. Reproduction. 2001;121:455-61 pubmed..The expression of the FSH and LH receptors was analysed by RT-PCR to study the role of these receptors in early mouse development...
- Bebia Z, Somers J, Liu G, Ihrig L, Shenker A, Zeleznik A. Adenovirus-directed expression of functional luteinizing hormone (LH) receptors in undifferentiated rat granulosa cells: evidence for differential signaling through follicle-stimulating hormone and LH receptors. Endocrinology. 2001;142:2252-9 pubmed..Analysis of messenger RNAs (mRNAs) revealed that activations of FSH and the LH receptors were comparable in the induction of alpha-inhibin and 3betahydroxysteroid dehydrogenase mRNAS: However, ..
- Bukovsky A, Ayala M, Dominguez R, Keenan J, Wimalasena J, McKenzie P, et al. Postnatal androgenization induces premature aging of rat ovaries. Steroids. 2000;65:190-205 pubmed..We suggest that mesenchymal cells regulate qualitative aspects of tissue-specific cells, and this function of mesenchymal cells is programmed during the critical period of development. ..
- Vischer H, Bogerd J. Cloning and functional characterization of a gonadal luteinizing hormone receptor complementary DNA from the African catfish (Clarias gariepinus). Biol Reprod. 2003;68:262-71 pubmed..alignment of the deduced amino acid sequence revealed that the cfLH-R had the highest identity with vertebrate LH receptors (>50%). Overall sequence identity between the cfLH-R and the African catfish FSH receptor (cfFSH-R) is 47%...
- Minegishi T, Nakamura K, Takakura Y, Miyamoto K, Hasegawa Y, Ibuki Y, et al. Cloning and sequencing of human LH/hCG receptor cDNA. Biochem Biophys Res Commun. 1990;172:1049-54 pubmed..While the protein is 85 and 87% identical overall with the previously cloned rat and porcine LH/hCG receptor respectively, the most highly conserved regions are the putative transmembrane segments (91 and 94% similarity, respectively). ..
- Kurtzman J, Wilson H, Rao C. A proposed role for hCG in clinical obstetrics. Semin Reprod Med. 2001;19:63-8 pubmed..While further work is needed, initial data strongly support this novel use of hCG in clinical obstetrics. ..
- Kremer H, Kraaij R, Toledo S, Post M, Fridman J, Hayashida C, et al. Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet. 1995;9:160-4 pubmed..These results have implications for the understanding of the development of the male genitalia. ..
- Jiang X, Russo I, Russo J. Alternately spliced luteinizing hormone/human chorionic gonadotropin receptor mRNA in human breast epithelial cells. Int J Oncol. 2002;20:735-8 pubmed..This difference in the expression of alternate splicing of LH/hCG receptor mRNA among the MCF-10F, MCF-7 and MDA-MB-231 cells, may explain the divergent response of these cells to HOXA1 activation by hCG. ..
- Jiang M, Lamminen T, Pakarinen P, Hellman J, Manna P, Herrera R, et al. A novel Ala(-3)Thr mutation in the signal peptide of human luteinizing hormone beta-subunit: potentiation of the inositol phosphate signalling pathway and attenuation of the adenylate cyclase pathway by recombinant variant hormone. Mol Hum Reprod. 2002;8:201-12 pubmed..Both LH forms bound to LH receptors with similar affinities...
- Bacich D, Rohan R, Norman R, Rodgers R. Characterization and relative abundance of alternatively spliced luteinizing hormone receptor messenger ribonucleic acid in the ovine ovary. Endocrinology. 1994;135:735-44 pubmed..The overall level of expression of LHR mRNA was greater in corpora lutea than follicles, but the relative abundance of the splice variants was similar in follicles and corpora lutea. ..
- Peters M, Teerds K, van der Gaag I, de Rooij D, van Sluijs F. Use of antibodies against LH receptor, 3beta-hydroxysteroid dehydrogenase and vimentin to characterize different types of testicular tumour in dogs. Reproduction. 2001;121:287-96 pubmed..Overall, this panel of antibodies can be very useful for determination of the identity of testicular tumours in which histological characterization is complicated and the pathogenesis of feminization is not clear...
- Zhang F, Poutanen M, Wilbertz J, Huhtaniemi I. Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice. Mol Endocrinol. 2001;15:172-83 pubmed
- Hamalainen T, Kero J, Poutanen M, Huhtaniemi I. Transgenic mice harboring murine luteinizing hormone receptor promoter/beta-galactosidase fusion genes: different structural and hormonal requirements of expression in the testis, ovary, and adrenal gland. Endocrinology. 2002;143:4096-103 pubmed
- Atger M, Misrahi M, Sar S, Le Flem L, Dessen P, Milgrom E. Structure of the human luteinizing hormone-choriogonadotropin receptor gene: unusual promoter and 5' non-coding regions. Mol Cell Endocrinol. 1995;111:113-23 pubmed..Primers and PCR conditions are described for the direct genomic sequencing of all the exons of the gene. This information should facilitate the study of pathological mutations of the receptor. ..
- McFarland K, Sprengel R, Phillips H, Kohler M, Rosemblit N, Nikolics K, et al. Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family. Science. 1989;245:494-9 pubmed..As revealed by RNA blot analysis and in situ hybridization, the 4.4-kilobase cognate messenger RNA is prominently localized in the rat ovary. ..
- Srisuparp S, Strakova Z, Fazleabas A. The role of chorionic gonadotropin (CG) in blastocyst implantation. Arch Med Res. 2001;32:627-34 pubmed..Thus, our results suggest that CG plays an important role in implantation in addition to its luteotrophic role. ..
- Kumar R, Ijiri S, Trant J. Molecular biology of channel catfish gonadotropin receptors: 1. Cloning of a functional luteinizing hormone receptor and preovulatory induction of gene expression. Biol Reprod. 2001;64:1010-8 pubmed..This pattern of expression correlates well with the reported expression of its ligand (LH) in fishes and concurs with the notion that LH is a key regulator of the periovulatory maturational events...
- Roche P, Ryan R. Purification, characterization, and amino-terminal sequence of rat ovarian receptor for luteinizing hormone/human choriogonadotropin. J Biol Chem. 1989;264:4636-41 pubmed..This study also describes a relatively simple technique for electroblotting and microsequencing that should be applicable to other membrane-bound hormone receptors. ..
- Xie Y, Wang H, Segaloff D. Extracellular domain of lutropin/choriogonadotropin receptor expressed in transfected cells binds choriogonadotropin with high affinity. J Biol Chem. 1990;265:21411-4 pubmed..Unexpectedly, it was also found that this truncated receptor is not secreted into the culture media but remains trapped within the cells. ..
- Rousseau Merck M, Misrahi M, Atger M, Loosfelt H, Milgrom E, Berger R. Localization of the human luteinizing hormone/choriogonadotropin receptor gene (LHCGR) to chromosome 2p21. Cytogenet Cell Genet. 1990;54:77-9 pubmed..Probes corresponding to human and porcine LH (luteinizing hormone) receptor cDNA were used for in situ hybridization to human chromosomes. This allowed us to assign the LH receptor gene to chromosome 2p21. ..
- 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;19:37-47 pubmed..The third phase may be characterized by the expression of full-length hCG/LH receptors on the trophoblasts themselves...
- van Tol H, van Eijk M, Mummery C, van den Hurk R, Bevers M. Influence of FSH and hCG on the resumption of meiosis of bovine oocytes surrounded by cumulus cells connected to membrana granulosa. Mol Reprod Dev. 1996;45:218-24 pubmed..This is supported by the fact that receptors for FSH, but not for LH, are transcribed in the cumulus and granulosa cells of these follicles. ..
- Inoue K, Nakamura K, Abe K, Hirakawa T, Tsuchiya M, Matsuda H, et al. Effect of transforming growth factor beta on the expression of luteinizing hormone receptor in cultured rat granulosa cells. Biol Reprod. 2002;67:610-5 pubmed..On the other hand, the decay curves for LH-R mRNA transcript in primary granulosa cells showed a significant increase in half-life after the addition of TGFbeta. ..
- Tsai Morris C, Buczko E, Wang W, Dufau M. Intronic nature of the rat luteinizing hormone receptor gene defines a soluble receptor subspecies with hormone binding activity. J Biol Chem. 1990;265:19385-8 pubmed..These features of the LH receptor are distinct from those of most other G protein-coupled receptors, which are intronless and contain their binding sites within the transmembrane region rather than the extracellular domain. ..
- Loosfelt H, Misrahi M, Atger M, Salesse R, Vu Hai Luu Thi M, Jolivet A, et al. Cloning and sequencing of porcine LH-hCG receptor cDNA: variants lacking transmembrane domain. Science. 1989;245:525-8 pubmed..The messenger RNA was expressed in COS-7 cells, yielding a protein that bound hCG with the same affinity as the testicular receptor. ..
- Shemesh M, Mizrachi D, Gurevich M, Stram Y, Shore L, Fields M. Functional importance of bovine myometrial and vascular LH receptors and cervical FSH receptors. Semin Reprod Med. 2001;19:87-96 pubmed..Because expression of the FSH receptor was maximal at the time of the FSH peak in the blood, we suggest a physiological role for FSH in the cervix relaxation and opening at estrus. ..
- Zaleska M, Waclawik A, Bodek G, Zezula Szpyra A, Li X, Janowski T, et al. Growth repression in diethylstilbestrol/dimethylbenz[a]anthracene-induced rat mammary gland tumor using Hecate-CGbeta conjugate. Exp Biol Med (Maywood). 2004;229:335-44 pubmed..The mechanism of Hecate-CGbeta conjugate action in repression of DES/DMBA-induced tumor growth needs to be further analyzed to clarify the molecular mechanisms of Hecate-CGbeta conjugate action in vivo. ..
- Gadkari R, Sandhya S, Sowdhamini R, Dighe R. The antigen binding sites of various hCG monoclonal antibodies show homology to different domains of LH receptor. Mol Cell Endocrinol. 2007;260-262:23-32 pubmed