Ultrastuctural localization of HCG and subunits in the human placenta and choriocarcinoma cell lines-morphological approach to secretory pathway.

Suemizu, Hiroshi; Osamura, Yoshiyuki

doi:10.1267/ahc.21.265

Cited by 11 publications

(5 citation statements)

References 10 publications

(8 reference statements)

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Section: Resultssupporting

confidence: 54%

“…These data reflect differences in the secretion behavior of CG compared with its pituitary homologue LH. The apical secretion of CG is consistent with its in vivo release, since CG enters the maternal blood lakes of the uterus via an apical route through the villous (1,(12)(13)(14).To examine the possibility of nonspecific transfer of CG and LH across the MDCK cell monolayer, conditioned media containing 35 S-labeled CG or LH from the MDCK cell-line was added to nontransfected MDCK cells grown on Transwell filters. After overnight incubation lysates and media from the apical and basolateral compartments were immunoprecipitated.…”

mentioning

confidence: 91%

“…LH is packaged into storage granules (8), subject to regulated exocytosis by secretagogues (9), and released via the basolateral surface of pituitary gonadotrope cells (10,11). In contrast, CG is secreted by an apical route through the villous and directly into the intervillous space created by the implanted placenta (1,(12)(13)(14). The molecular basis by which the intracellular trafficking of CG is directed to exit the chorionic villi into the maternal lumen is unknown.…”

mentioning

confidence: 99%

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Evolution of Lutropin to Chorionic Gonadotropin Generates a Specific Routing Signal for Apical Release in Vivo

Jablonka‐Shariff¹,

Campayo

Boime

2002

Journal of Biological Chemistry

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One of the fundamental differences among mammals is the mechanism of maintaining the corpus luteum of pregnancy. Placentation in primates is associated with the production of the glycoprotein hormone chorionic gonadotropin (CG), which is secreted into the maternal serum and stimulates progesterone synthesis from the corpus luteum, which is essential for early development of the embryo. CG together with the pituitary hormones lutropin (LH), follitropin, and thyrotropin constitute the family of glycoprotein hormones comprised of a common ␣ subunit and a hormone-specific ␤ subunit. The LH␤ and CG␤ subunits share 85% amino acid sequence identity, and functionally LH and CG are interchangeable. CG␤ evolved by a recent gene duplication event from the LH␤ locus, and despite the close relationship between them, their modes of secretion are quite different. CG release from the placenta is apically directed, whereas LH is released from the basal side of the cell, and the determinant(s) for this redirected trafficking are unknown. Here, using the polarized Madin-Darby canine kidney (MDCK) cell line, we provide evidence for the molecular basis of the different secretory patterns of LH and CG in vivo. The apical targeting of CG is programmed by a carboxyl-terminal sequence, which encodes a novel sorting signal. It is also apparent that the presence of the O-linked oligosaccharides in the CTP sequence contributes to this apical routing. The CTP, which is absent in LH, redirects CG to the maternal serum and permits the unique arrangement for primate placentation. Our data also show that the MDCK cells can distinguish the different secretory pathways for the gonadotropins and will be a valuable model for elucidating the determinants associated with the unique sorting of these functionally related hormones.The evolution of primates is associated with a fundamental change in the morphogenesis of the placenta (1, 2). Placentation in primates is coupled to the synthesis of glycoprotein hormone chorionic gonadotropin (CG), 1 which is secreted into the maternal serum and stimulates progesterone synthesis from the corpus luteum, thereby allowing early implantation and development of the embryo (3, 4). CG and its pituitary counterpart, lutropin (LH), comprise a family of heterodimeric glycoprotein hormones, including follitropin and thyrotropin, that share a common ␣ subunit, but differ in their hormonespecific ␤ subunits (5). Although the ␤ subunits determine biological specificity of each hormone, there is significant structural similarity between them. This is most evident for the LH␤ and CG␤ subunits, which share 85% amino acid identity in the first 114 amino acids (6). A major difference between the two subunits is the presence in the CG␤ subunit of a 31-amino acid carboxyl-terminal extension (CTP) compared with a shorter 7-amino acid stretch in LH␤ (see "Results").The CG␤ subunit is specific to primates and evolved by a gene duplication event from the LH␤ locus (7); functionally the two are interchangeable. Similar to other mamma...

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Section: Resultssupporting

confidence: 54%

mentioning

confidence: 91%

mentioning

confidence: 99%

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Evolution of Lutropin to Chorionic Gonadotropin Generates a Specific Routing Signal for Apical Release in Vivo

Jablonka‐Shariff¹,

Campayo

Boime

2002

Journal of Biological Chemistry

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“…This means that hCG has the ability to be stored if the cell has storage granules. No large dense-core storage granules have been identified in placenta and choriocarcinoma cell lines [20], but stimulation of hCG release by GnRH and KCl from choriocarcinoma cells [15] and an increase in serum hCG shortly after GnRH administration in pregnant women [16] support the idea that there may be a small number of granules in placenta and malignant trophoblastic tissues.…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-Releasing Hormone-Induced Elevation of Serum hCG in Choriocarcinoma: A Case Report.

et al. 1998

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Abstract. We evaluated the effect of GnRH on the serum hCG level in gestational trophoblastic disease (GTD). Five patients with GTD were studied. Three patients had hydatidiform mole (two complete and one partial mole) and two had choriocarcinoma. Blood samples were collected immediately before and 30, 60 min after the 100 µg GnRH iv injection, followed by hCG assay. Only one case of choriocarcinoma demonstrated an hCG increase after intravenous administration of GnRH (positive GnRH test). In that case, the hCG level dropped to the normal range after eight cycles of chemotherapy but the GnRH test was still positive, suggesting the existence of viable cancer cells. Since the GnRH test became negative, no increase in hCG has been observed, indicating that the patient achieved complete remission. Although a positive GnRH test is not common in GTD, GnRH test before treatment might be useful to find a positive case where the test can be repeated to determine complete remission and the time when the chemotherapy may be discontinued.

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“…By contrast, FSH is released constitutively into the blood stream and its secretion is tightly coupled to synthesis [8][9][10]. CG is released constitutively from placenta but is apically directed through the villous to the uterine luminal compartment created by the implanted placenta [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Luteinizing Hormone and Follicle-Stimulating Hormone Exhibit Different Secretion Patterns from Cultured Madin-Darby Canine Kidney Cells

Jablonka‐Shariff

Boime

2004

Biology of Reproduction

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LH, FSH, and chorionic gonadotropin (CG) are comprised of a common alpha subunit and a hormone-specific beta subunit. Using Madin-Darby canine kidney (MDCK) epithelial cells to examine the polarized secretion of human CG/LH, we previously reported that CG and LH were detected in the apical and basolateral compartments, respectively, and the carboxyl terminal end of the CGbeta subunit contains a strong apical signal. Here we show that the carboxyl seven amino acids in the LHbeta subunit contribute to the basolateral secretion of LH, and an LH chimera bearing the CGbeta apical signal is redirected from the basolateral to the apical compartments. Because LH and FSH are synthesized in the same cell, we also compared the secretion polarity of LH with FSH. MDCK cells expressing the FSH dimer displayed an almost equal distribution of protein into the apical and basolateral compartments. Given that the LHbeta and CGbeta carboxy terminal sequences, which differ from that in the FSHbeta subunit, occupy a pivotal role in their polarized behavior, the results support the hypothesis that pituitary exit of LH and FSH occur via different secretion pathways, and are released spatially from the pituitary via different circulatory routes.

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Ultrastuctural localization of HCG and subunits in the human placenta and choriocarcinoma cell lines-morphological approach to secretory pathway.

Cited by 11 publications

References 10 publications

Evolution of Lutropin to Chorionic Gonadotropin Generates a Specific Routing Signal for Apical Release in Vivo

Evolution of Lutropin to Chorionic Gonadotropin Generates a Specific Routing Signal for Apical Release in Vivo

Gonadotropin-Releasing Hormone-Induced Elevation of Serum hCG in Choriocarcinoma: A Case Report.

Luteinizing Hormone and Follicle-Stimulating Hormone Exhibit Different Secretion Patterns from Cultured Madin-Darby Canine Kidney Cells

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