378 results on '"Oride A"'
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352. Prolonged stimulation with thyrotropin-releasing hormone and pituitary adenylate cyclase-activating polypeptide desensitize their receptor functions in prolactin-producing GH3 cells
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Mijiddorj, Tselmeg, Kanasaki, Haruhiko, Unurjargal, Sukhbaatar, Oride, Aki, Purwana, Indri, and Miyazaki, Kohji
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THYROTROPIN releasing factor , *ADENYLATE cyclase , *POLYPEPTIDES , *PROLACTIN , *PITUITARY hormones , *MESSENGER RNA - Abstract
Abstract: We used somatolactotroph GH3 cells to examine changes in response to stimulation with thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP) after sustained treatment with these peptides. TRH and PACAP increased prolactin promoter activity in mock- and PACAP type 1 receptor (PAC1R)-transfected cells. When the cells were pretreated with TRH for 48h, the response of the prolactin promoter to both TRH and PACAP was diminished. Similarly, in PAC1R-transfected GH3 cells pretreated with PACAP, the effects of TRH and PACAP on the prolactin promoter were eliminated. The stimulation of prolactin mRNA expression by TRH and PACAP was eliminated by prolonged pretreatment with these peptides in PAC1R-transfected cells. Both the serum response element (SRE) promoters and cAMP response element (CRE) promoters were activated by TRH and PACAP in either mock- or PAC1R-transfected cells. Pretreatment for 48h with TRH also eliminated the effects of TRH and PACAP on the SRE and CRE promoters, and pretreatment of PAC1R-transfected cells with PACAP for 48h reduced the responses of the SRE and CRE promoters to TRH and PACAP. These observations demonstrated that sustained stimulation with TRH and PACAP desensitizes their own and each other’s receptors. [Copyright &y& Elsevier] more...
- Published
- 2013
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353. The role of KNDy neurons in human reproductive health.
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Oride A and Kanasaki H
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- Humans, Animals, Female, Reproductive Health, Neurokinin B metabolism, Neurokinin B genetics, Hypogonadism genetics, Hypogonadism metabolism, Receptors, Kisspeptin-1 genetics, Receptors, Kisspeptin-1 metabolism, Dynorphins metabolism, Dynorphins genetics, Reproduction physiology, Kisspeptins metabolism, Kisspeptins genetics, Kisspeptins physiology, Neurons metabolism, Gonadotropin-Releasing Hormone metabolism, Arcuate Nucleus of Hypothalamus metabolism
- Abstract
In the early 2000s, metastin, an endogenous ligand for G protein-coupled receptor 54 (GPR54), was discovered in human placental extracts. In 2003, GPR54 receptor mutations were found in a family with congenital hypogonadotropic hypogonadism. Metastin was subsequently renamed kisspeptin after its coding gene, Kiss1. Since then, studies in mice and other animals have revealed that kisspeptin is located at the apex of the hypothalamic-pituitary-gonadal axis and regulates reproductive functions by modulating gonadotropin-releasing hormone (GnRH). In rodents, kisspeptin (Kiss1) neurons localize to two regions, the hypothalamic arcuate nucleus (ARC) and the anteroventral periventricular nucleus (AVPV). ARC Kiss1 neurons co-express neurokinin B (NKB) and dynorphin and are thus termed KNDy neurons. Kiss1 neurons in humans are concentrated in the infundibular nucleus (equivalent to the ARC), with few Kiss1 neurons localized to the preoptic area (equivalent to the AVPV), and the mechanisms underlying GnRH surge secretion in humans are poorly understood. However, peripheral administration of kisspeptin to humans promotes gonadotropin secretion, and administration of kisspeptin to patients with hypothalamic amenorrhea or congenital hypogonadotropic hypogonadism restores the pulsatile secretion of GnRH/luteinizing hormone. Thus, kisspeptin undoubtedly plays an important role in reproductive function in humans. Studies are currently underway to develop kisspeptin receptor agonists or antagonists for clinical application. Modification of KNDy neurons by NKB agonists/antagonists is also being attempted to develop therapeutic agents for various menstrual abnormalities, including polycystic ovary syndrome and menopausal hot flashes. Here, we review the role of kisspeptin in humans and its clinical applications. more...
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- 2024
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354. Impact of current and previous sperm findings on outcomes of intrauterine insemination.
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Taniguchi M, Kanasaki H, Oride A, Okada H, Imamura K, and Kyo S
- Abstract
Purpose: To examine the association between semen characteristics and outcomes of intrauterine insemination (IUI)., Methods: This retrospective analysis examined 1380 IUI procedures involving 421 couples. The association of clinical pregnancy with pre- and post-wash sperm characteristics was assessed., Results: Pre- and post-wash sperm characteristics did not differ between IUI cycles that resulted in pregnancy and those that did not. When the motility of pre-wash sperm was below the normal range (<42%) established by the World Health Organization (WHO), the pregnancy rate was significantly lower. In the IUI cycles when post-wash sperm motility was below the WHO standard, pregnancy was not achieved. The frequency of improvement in post-wash sperm motility in repeated IUI cycles appeared to correlate with the success of future IUI cycles. At the fourth IUI cycle, pregnancy was not achieved unless the post-wash sperm motility was normal in at least two of three attempts. When post-wash sperm concentration was below the normal range, the woman's age did not affect the IUI outcomes., Conclusions: Sperm motility above the lower limit of the WHO criteria in post-wash semen samples is an important factor in IUI outcomes., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.) more...
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- 2024
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355. Changes in pituitary gonadotropin subunits and hypothalamic Kiss-1 gene expression by administration of sex steroids in ovary-intact female rats.
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Yacca SS, Kanasaki H, Tumurbaatar T, Cairang Z, Oride A, Okada H, and Kyo S
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- Rats, Female, Animals, Hypothalamus metabolism, Gonadotropins, Pituitary genetics, Gonadotropins, Pituitary metabolism, Gonadotropin-Releasing Hormone genetics, Gonadotropin-Releasing Hormone metabolism, Estradiol pharmacology, RNA, Messenger metabolism, Dihydrotestosterone pharmacology, Gene Expression, Ovary, Kisspeptins genetics, Kisspeptins metabolism
- Abstract
Objective: We examined how the sex steroids influence the synthesis of gonadotropins., Materials and Methods: The effects of sex steroids estradiol (E2), progesterone (P4), and dihydrotestosterone (DHT) in pituitary gonadotroph cell model (LβT2 cells) in vitro and ovary-intact rats in vivo were examined. The effects of sex steroids on Kiss1 gene expression in the hypothalamus were also examined in ovary-intact rats., Results: In LβT2 cells, E2 increased common glycoprotein alpha (Cga) and luteinizing hormone beta (Lhb) subunit promoter activity as well as their mRNA expression. Although gonadotropin subunit promoter activity was not modulated by P4, Cga and Lhb mRNA expression was increased by P4. DHT inhibited Cga and Lhb mRNA expression with a concomitant decrease in their promoter activity. During the 2-week administration of exogenous E2 to ovary-intact rats, the estrous cycle determined by vaginal smears was disrupted. P4 or DHT administration completely eliminated the estrous cycle. Protein expression of all three gonadotropin subunits within the pituitary gland was inhibited by E2 or P4 treatment in vivo; however, DHT reduced Cga expression but did not modulate Lhb or follicle-stimulating hormone beta subunit expression. E2 administration significantly repressed Kiss1 mRNA expression in a posterior hypothalamic region that included the arcuate nucleus. P4 and DHT did not modulate Kiss1 mRNA expression in this region. In contrast, P4 administration significantly inhibited Kiss1 mRNA expression in the anterior region of the hypothalamus that included the anteroventral periventricular nucleus. The expression of gonadotropin-releasing hormone (Gnrh) mRNA in the anterior hypothalamic region, where the preoptic area is located, appeared to be decreased by treatment with E2 and P4., Conclusion: Our findings suggest that sex steroids have different effects in the hypothalamus and pituitary gland., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...
- Published
- 2024
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356. Acute abdomen by red degeneration of a parasitic leiomyoma: A case report and literature review.
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Yoshida R, Makihara Y, Miyamoto A, Araki H, Ando S, Yoshizako T, Oride A, and Kaji Y
- Abstract
A 43-year-old woman, with a history of uterine fibroids and multiple myomectomy, presented with acute lower abdominal pain. Computed tomography revealed multiple tumors, including a high-density mass in the left lower abdomen indicative of a parasitic leiomyoma undergoing red degeneration. This uncommon condition is due to acute occlusion, often caused by peripheral venous thrombosis at the fibroid edge. The diagnosis was corroborated by distinctive findings on magnetic resonance imaging and computed tomography. Notably, high signal intensity on T1-weighted images (T1WI) suggested methemoglobin presence due to hemorrhagic infarction, whereas low signal intensity on T2-weighted images (T2WI) indicated deoxyhemoglobin. Symptom improvement followed treatment with analgesics. This case underscores the significance of considering parasitic myomas in the differential diagnosis of intraperitoneal tumors after myomectomy and proposes that vascular torsion from mechanical stress on the mobile mesentery may contribute to red degeneration in such tumors. In this report, we detail the imaging characteristics and clinical progression of red degeneration in a parasitic leiomyoma, emphasizing the importance of this diagnosis in patients with a history of uterine surgery., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.) more...
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- 2024
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357. Impact of Ovariectomy on the Anterior Pituitary Gland in Female Rats.
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Oride A, Kanasaki H, Tumurbaatar T, Tumurgan Z, Okada H, Cairang Z, and Satoru K
- Abstract
Ovariectomy (OVX) causes a depletion of circulating estradiol (E2) and influences hypothalamic kisspeptin neurons, which govern gonadotropin-releasing hormone (GnRH) release and ultimately gonadotropin secretion. In this study, we examined the changes induced by OVX on the anterior pituitary gland in female rats. OVX significantly increased the mRNA expression of gonadotropin α , luteinizing hormone (LH) β , and follicle-stimulating hormone (FSH) β subunits within the pituitary gland compared with control (sham-operated) rats, and this was completely suppressed by E2 supplementation. High-dose dihydrotestosterone supplementation also prevented the OVX-induced increase in the expression of the three gonadotropin subunits. GnRH receptor mRNA expression within the pituitary was significantly increased in OVX rats, and this increase was completely inhibited by E2 supplementation. The mRNA expression of the receptors for adenylate cyclase-activating polypeptide and kisspeptin was unchanged by OVX. Although the mRNA levels of inhibin α , β A, and β B subunits within the pituitary gland were not modulated by OVX, follistatin gene expression within the pituitary gland was increased by OVX, and this increase was completely inhibited by E2 supplementation after OVX. In experiments using a pituitary gonadotroph cell model (L β T2 cells), follistatin itself did not modulate the mRNA expression of gonadotropin LH β and FSH β subunits, and the GnRH-induced increase in the expression of these genes was slightly inhibited in the presence of follistatin. Our current observations suggest that OVX induces several characteristic changes in the pituitary gland of rats., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Aki Oride et al.) more...
- Published
- 2023
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358. Lymphoma during pregnancy in Japan: a multicenter retrospective cohort study.
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Onishi C, Nishikori M, Yakushijin K, Kurahashi S, Nakazawa H, Takamatsu Y, Hashimoto Y, Tatetsu H, Yuichiro Nawa, Yoshida M, Kobayashi T, Oyake T, Yano S, Oride A, and Suzuki R
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- Adult, Female, Follow-Up Studies, Hodgkin Disease drug therapy, Hodgkin Disease mortality, Humans, Incidence, Japan epidemiology, Lymphadenopathy epidemiology, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin mortality, Pneumonia, Pneumocystis epidemiology, Pregnancy, Pregnancy Complications, Infectious epidemiology, Pregnancy Complications, Neoplastic drug therapy, Pregnancy Complications, Neoplastic mortality, Pregnancy Outcome, Retrospective Studies, Survival Rate, Young Adult, Hodgkin Disease epidemiology, Lymphoma, Non-Hodgkin epidemiology, Pregnancy Complications, Neoplastic epidemiology
- Abstract
Objective: This study was conducted to characterize lymphoma occurring during pregnancy and to investigate the outcomes of the patients and the fetuses., Methods: Clinical data were gathered retrospectively from 29 patients at 13 participating institutions, and data from 28 eligible patients were analyzed., Results: Six (21%) patients had Hodgkin lymphoma (HL) and 22 (79%) patients had non-Hodgkin lymphoma (NHL). All patients with HL presented with lymphadenopathy, but 15 (68%) of the 22 patients with NHL presented with extranodal sites only. At the median follow-up period of 1325 (range 6-4461) days, the 5-year overall survival rate was 63% for patients with NHL and 100% for patients with HL. Three of the 13 patients who received chemotherapy during pregnancy (23%) developed Pneumocystis jiroveci pneumonia (PCP). There was 1 intrauterine fetal death, 1 spontaneous abortion in the first trimester, and 15 (54%) preterm births., Conclusion: This study showed a higher proportion of NHL than HL during pregnancy in Japan, which was inconsistent with the proportions observed in Western countries. The high incidence of maternal PCP and preterm birth suggested the need for improvements in our management of lymphoma during pregnancy., (© 2022. Japanese Society of Hematology.) more...
- Published
- 2022
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359. Reproductive prognosis of patients with hypogonadotropic hypogonadism: Retrospective review of 16 cases with amenorrhea.
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Oride A, Kanasaki H, Okada H, and Kyo S
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- Female, Gonadotropins, Humans, Pregnancy, Prognosis, Retrospective Studies, Amenorrhea etiology, Hypogonadism complications
- Abstract
Aim: The aim of this study was to evaluate the general characteristics, menstruation status, and fertility outcomes of patients with hypogonadotropic hypogonadism (HH)., Methods: We evaluated 16 patients with HH who visited our institution between April 2012 and March 2016 with a complaint of amenorrhea., Results: Four (25%) patients had primary amenorrhea and the remaining 12 (75%) cases had secondary amenorrhea. Among the patients with primary amenorrhea, weight loss was considered to be the underlying cause in one (25%) patient, whereas the remaining three (75%) cases were idiopathic HH. Among HH cases with secondary amenorrhea, six (50%) developed amenorrhea following weight loss, whereas the remaining six cases were of unknown etiology. Among the 16 patients with HH, we observed the sporadic restart of the menstrual cycle in four (25%) women during follow-up. Infertility treatment was administered to nine patients with HH who wished to become pregnant. Clomiphene citrate was effective in four patients with secondary amenorrhea and induced follicular development. Seven of nine patients with HH (77.8%) became pregnant following infertility treatment. In some cases of HH, the serum levels of gonadotropin increased sporadically during follow-up, regardless of the recovery of menstruation. We followed one patient with HH for more than 20 years. Although her gonadotropin levels were generally low and sometimes fluctuated without spontaneous menstruation, they increased dramatically to menopausal levels at 50 years of age. However, they again decreased to hypogonadotropic levels., Conclusion: As the pathophysiology varied widely among patients, the etiologic factors underlying HH might also vary., (© 2021 Japan Society of Obstetrics and Gynecology.) more...
- Published
- 2021
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360. Effect of anti-Müllerian hormone on the regulation of pituitary gonadotropin subunit expression: roles of kisspeptin and its receptors in gonadotroph LβT2 cells.
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Tumurbaatar T, Kanasaki H, Tumurgan Z, Oride A, Okada H, and Kyo S
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- Animals, Cell Line, Follicle Stimulating Hormone, beta Subunit genetics, Gene Expression Regulation drug effects, Gene Knockdown Techniques, Gonadotrophs drug effects, Gonadotropin-Releasing Hormone pharmacology, Kisspeptins genetics, Luteinizing Hormone, beta Subunit genetics, Mice, RNA, Small Interfering, Receptors, Kisspeptin-1 genetics, Anti-Mullerian Hormone pharmacology, Gonadotrophs metabolism, Gonadotropins, Pituitary genetics, Kisspeptins physiology, Receptors, Kisspeptin-1 physiology
- Abstract
Anti-Müllerian hormone (AMH) is primarily produced by ovarian granulosa cells and contributes to follicle development. AMH is also produced in other tissues, including the brain and pituitary; however, its roles in these tissues are not well understood. In this study, we examined the effect of AMH on pituitary gonadotrophs. We detected AMH and AMH receptor type 2 expression in LβT2 cells. In these cells, the expression of FSHβ- but not α- and LHβ-subunits increased significantly as the concentration of AMH increased. LβT2 cells expressed Kiss-1 and Kiss-1R. AMH stimulation resulted in decreases in both Kiss-1 and Kiss-1R. The siRNA-mediated knockdown of Kiss-1 in LβT2 cells did not alter the basal expression levels of α-, LHβ-, and FSHβ-subunits. In LβT2 cells overexpressing Kiss-1R, exogenous kisspeptin stimulation significantly increased the expression of all three gonadotropin subunits. However, kisspeptin-induced increases in these subunits were almost completely eliminated in the presence of AMH. In contrast, GnRH-induced increases in the three gonadotropin subunits were not modulated by AMH. Our observations suggested that AMH acts on pituitary gonadotrophs and induces FSHβ-subunit expression with concomitant decreases in Kiss-1 and Kiss-1R gene expression. Kisspeptin, but not GnRH-induced gonadotropin subunit expression, was inhibited by AMH, suggesting that it functions in association with the kisspeptin/Kiss-1R system in gonadotrophs. more...
- Published
- 2021
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361. Effect of anti-Müllerian hormone in hypothalamic Kiss-1- and GnRH-producing cell models.
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Oride A, Kanasaki H, Tumurbaatar T, Tumurgan Z, Okada H, and Kyo S
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- Animals, Arcuate Nucleus of Hypothalamus metabolism, Brain embryology, Cell Line, Cells, Cultured, Gonads, Hypothalamo-Hypophyseal System, Hypothalamus, Anterior metabolism, Neurons, RNA, Messenger analysis, Rats, Anti-Mullerian Hormone pharmacology, Gene Expression drug effects, Gonadotropin-Releasing Hormone genetics, Hypothalamus metabolism, Kisspeptins genetics
- Abstract
Purpose: Anti-Müllerian hormone (AMH) is one of the local factors involved in follicle development. In addition, AMH and its receptor are broadly expressed throughout the body. In this study, we examined how AMH modifies gene expression of Kiss-1 and GnRH. Materials and methods: mHypoA-50 and mHypoA-55 cells were originated from the hypothalamic anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC), respectively, and these cells are known as Kiss-1 (which encodes kisspeptin) expressing cell models. These cells also express gonadotropin-releasing hormone (GnRH) genes. Our experiments were performed useing these cell models. Results: Both mHypoA-50 and mHypoA-55 hypothalamic cells expressed AMH and AMH receptor type 2 (AMHR2). Exogenous AMH failed to alter the expression levels of the Kiss-1 gene in both cell models but significantly increased GnRH gene expression by 1.73 ± 0.2-fold at 100 pM in mHypoA-50 AVPV cells and by 1.74 ± 0.17-fold at 1 nM in mHypoA-55 ARC cells. AMH also augmented GnRH protein expression in both cell models. Similar to the phenomenon observed in the hypothalamic cell lines, 100 pM AMH significantly increased GnRH, but not Kiss-1, mRNA expression in primary cultures of fetal rat brain cells. Kisspeptin-10 (KP10) increased Kiss-1 gene expression in mHypoA-55 ARC cells but this was blocked by AMH. AMH did not alter the expression of the kisspeptin receptor (Kiss1R) or that of neurokinin B or dynorphin A in mHypoA-55 ARC cells. Conclusions: It was demonstrated that AMH participates in hypothalamic-pituitary-gonadal axis control by stimulating GnRH expression. In addition, AMH might be a potent repressor of Kiss-1 gene expression induced by KP10. more...
- Published
- 2021
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362. Detection of pure Leydig cell ovarian tumor not visible on imaging by selective venous blood sampling in a woman with secondary amenorrhea and hirsutism: A case report.
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Oride A, Kanasaki H, Okada H, and Kyo S
- Abstract
A 39-year-old woman (gravida 1, para 1) was referred to a university hospital with a high serum testosterone level and secondary amenorrhea, hirsutism, and weight gain. Her voice was deep, and hirsutism was observed on her chin, arms, and back. She also had clitoromegaly. Her serum testosterone levels were markedly elevated (testosterone 11.1 ng/mL, free testosterone 15.5 pg/mL). Transvaginal ultrasonography and magnetic resonance imaging did not reveal any tumors in the pelvic organs, including the uterus and ovaries. Enhanced computed tomography revealed no abnormalities in either adrenal gland. Blood sampling from the inferior vena cava, left renal vein, and the ovarian veins on both sides revealed an extremely high testosterone level (391 ng/mL) in blood from the right ovarian vein. Laparoscopic right oophorectomy was performed and the pathologic diagnosis was a Leydig cell tumor (1.5 × 1.5 × 1.3 cm). Her serum testosterone level decreased rapidly following oophorectomy (0.3 ng/mL on postoperative day 2). Her menstrual cycle had recovered spontaneously by 2 months after surgery and she noticed improvement in the hirsutism 4 months after the operation., (© 2021 The Authors.) more...
- Published
- 2021
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363. Comparative Retrospective Study of Tension-Free Vaginal Mesh Surgery, Native Tissue Repair, and Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse Repair.
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Kanasaki H, Oride A, Hara T, and Kyo S
- Abstract
Methods: We identified that 308 women who had undergone surgical repair of POP were followed up for at least 6 months. Recurrence rates of POP after tension-free vaginal mesh (TVM) surgery ( n = 243), native tissue repair (NTR) (vaginal hysterectomy with colpopexy, anterior and posterior colpoplasty, or circumferential suturing of the levator ani muscles and apical repair by transvaginal sacrospinous ligament fixation (SSLF)) (NTR; n = 31), and laparoscopic sacrocolpopexy after subtotal hysterectomy (LSC; n = 34) were compared. Presence of mesh erosion was also recorded., Results: Patients who underwent LSC were significantly younger (65.32 ± 3.23 years) than those who underwent TVM surgery (69.61 ± 8.31 years). After TVM surgery, the rate of recurrence (over POP-Q stage II) was 6.17% (15/243) and was highest in patients with advanced POP. The recurrence rate in patients who underwent NTR procedure was 3.23% (1/34) and that in patients who underwent LSC was 11.76% (4/11). There was no statistically significant difference in the recurrence rate between the three types of surgery. There were 13 cases (5.35%) of mesh erosion after TVM surgery and none after LSC surgery. The risk of mesh erosion was correlated with having had total TVM surgery but not with patient age or POP stage. Repeat procedures were performed in 5 women (2.14%) who underwent TVM surgery and 1 (2.94%) who underwent LSC. No patient underwent repeat surgery after NTR. There was no statistically significant difference in the reoperation rate between the three types of surgery., Conclusion: Our study suggested that TVM surgery, NTR, and LSC have comparable outcomes as for the postoperative recurrence rate and mesh erosion. However, the outcomes of each technique need to be carefully evaluated over a long period of time., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Haruhiko Kanasaki et al.) more...
- Published
- 2020
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364. Effects of the Fertility Drugs Clomiphene Citrate and Letrozole on Kiss-1 Expression in Hypothalamic Kiss-1-Expressing Cell Models.
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Oride A, Kanasaki H, Tumurbaatar T, Zolzaya T, Okada H, Hara T, and Kyo S
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- Animals, Cell Line, Estradiol administration & dosage, Estrogen Receptor Antagonists administration & dosage, Gene Expression drug effects, Mice, Receptors, Estrogen metabolism, Clomiphene administration & dosage, Fertility Agents, Female administration & dosage, Hypothalamus drug effects, Hypothalamus metabolism, Kisspeptins metabolism, Letrozole administration & dosage, Neurons drug effects, Neurons metabolism
- Abstract
Clomiphene citrate (CC) and letrozole stimulate the hypothalamic-pituitary-ovarian axis and are used widely as oral fertility drugs to induce folliculogenesis. We examined whether these drugs increase Kiss-1 expression in hypothalamic cell models. We utilized two hypothalamic cell models, mHypoA-50 and mHypoA-55, which originated from Kiss-1 neurons in the anteroventral periventricular (AVPV) nucleus and arcuate (ARC) nucleus of the mouse hypothalamus, respectively. The cells were stimulated with CC or letrozole, after which Kiss-1 mRNA expression was determined. CC stimulated Kiss-1 gene expression in mHypoA-50 and mHypoA-55 cells. The basal expression of Kiss-1 was significantly increased in the presence of estradiol (E2) in mHypoA-50 cells, and the CC-induced increase in Kiss-1 expression was not observed in the presence of E2 in these cells. In contrast, E2 did not modify the basal expression of Kiss-1 in mHypoA-55 cells, and CC-induced Kiss-1 expression was still observed in the presence of E2. The significant increase in Kiss-1 gene expression in mHypoA-50 and mHypoA-55 cells was blunted in the presence of estrogen receptor antagonists. Aromatase was expressed in mHypoA-50 and mHypoA-55 cells. Letrozole, an aromatase inhibitor, increased Kiss-1 expression in mHypoA-55 ARC cells but not in mHypoA-50 AVPV cells. Although the basal expression of Kiss-1 was increased by E2, letrozole did not modulate Kiss-1 expression in mHypoA-50 cells. Letrozole-induced Kiss-1 gene expression in mHypoA-55 cells was not modulated in the presence of E2. The fertility drugs CC and letrozole modulated Kiss-1 expression in hypothalamic cell models. more...
- Published
- 2020
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365. Postoperative Outcomes Following Tension-Free Vaginal Mesh Surgery for Pelvic Organ Prolapse: A Retrospective Study.
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Oride A, Kanasaki H, Hara T, and Kyo S
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- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Incidence, Japan epidemiology, Middle Aged, Pelvic Organ Prolapse complications, Postoperative Complications epidemiology, Recurrence, Retrospective Studies, Treatment Outcome, Urinary Incontinence, Stress epidemiology, Urinary Incontinence, Stress physiopathology, Gynecologic Surgical Procedures methods, Pelvic Organ Prolapse surgery, Postoperative Complications prevention & control, Suburethral Slings, Urinary Incontinence, Stress prevention & control, Urination physiology
- Abstract
Purpose: We retrospectively reviewed the postoperative outcomes of patients who underwent tension-free vaginal mesh (TVM) surgery in our institution., Methods: In total, 195 TVM surgeries were performed at the Shimane University School of Medicine from January 2010 to May 2016 in patients with Pelvic Organ Prolapse-Quantification (POP-Q) stage II or higher. Perioperative complications and problems arising following surgery were assessed from medical charts., Results: Among the 195 patients, only 1 patient required blood transfusion due to massive intraoperative blood loss. None of the patients experienced intraoperative complications, such as injury to the bladder or rectum during surgery. Mesh exposure was observed in 10 patients (5.1%). Overall, 6 of these 10 patients were asymptomatic, and surgical treatment was required in only 1 patient. Mesh exposure occurred at significantly higher frequencies in patients aged less than 60 years. Postoperative recurrence of POP, which was defined as recurrence over POP-Q stage 2, was noted in 13 of the 195 patients (6.6%). Re-operation was performed in 1 patient in whom recurrence was observed within 3 months postoperatively. Recurrence of POP was likely to occur in patients with higher POP-Q stages. Overall, 31 of the 195 patients (15.9%) required medication for postoperative stress urinary incontinence (SUI) after surgery. Among these, 2 patients underwent surgical treatment for SUI., Conclusion: Outcomes following the TVM procedure were satisfactory. However, caution should be exercisedagainst mesh exposure in younger patients and recurrence of POP in patients with advanced POP-Q stage. more...
- Published
- 2019
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366. Role of kisspeptin and Kiss1R in the regulation of prolactin gene expression in rat somatolactotroph GH3 cells.
- Author
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Hara T, Kanasaki H, Tumurbaatar T, Oride A, Okada H, and Kyo S
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- Animals, Cell Line, Cyclic AMP-Dependent Protein Kinases genetics, Estradiol pharmacology, Gene Expression Regulation drug effects, Humans, MAP Kinase Signaling System genetics, Pituitary Adenylate Cyclase-Activating Polypeptide pharmacology, Pituitary Gland metabolism, Promoter Regions, Genetic genetics, Rats, Signal Transduction genetics, Thyrotropin-Releasing Hormone genetics, Thyrotropin-Releasing Hormone metabolism, Gene Expression Regulation genetics, Kisspeptins genetics, Prolactin biosynthesis, Prolactin genetics, Receptors, Kisspeptin-1 genetics
- Abstract
Hypothalamic kisspeptin is a known principal activator of gonadotropin-releasing hormone neurons and governs the hypothalamic-pituitary-gonadal axis. Previous reports have shown that kisspeptin is also released into the hypophyseal portal circulation and directly affects the anterior pituitary. In this study, we examined the direct effect of kisspeptin on pituitary prolactin-producing cells. The rat pituitary somatolactotroph cell line GH3 expresses the kisspeptin receptor (Kiss1R); however, in these cells, kisspeptin failed to stimulate prolactin-promoter activity. When GH3 cells overexpressed Kiss1R, kisspeptin clearly increased prolactin-promoter activity, with a concomitant increase in extracellular signal-regulated kinase (ERK) and cAMP/protein kinase A (PKA) signaling pathways. In the experiments using GH3 cells overexpressing Kiss1R, kisspeptin did not potentiate thyrotropin-releasing hormone (TRH)-induced prolactin-promoter activity, but it potentiated the pituitary adenylate cyclase-activating polypeptide-induced prolactin-promoter activity, with a concomitant enhancement of ERK and PKA signaling pathways. Although the basal and TRH-induced prolactin-promoter activities were not modulated by increasing amounts of Kiss1R expression in GH3 cells, kisspeptin-stimulated prolactin-promoter activity was increased by the amount of Kiss1R overexpression. Endogenous Kiss1r mRNA expression in GH3 cells was significantly increased by treatment with estradiol (E2) but not by TRH. In addition, kisspeptin's ability to stimulate prolactin-promoter activity was restored after E2 treatment in non-transfected GH3 cells. Our current observations suggest that kisspeptin might have a direct effect on prolactin expression in the anterior pituitary prolactin-producing cells under the influence of E2, which may regulate Kiss1R expression and function. more...
- Published
- 2019
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367. Comparison of Postoperative Short-Term Outcomes between Tension-Free Vaginal Mesh Surgery Using the Capio™ SLIM Suture Capturing Device and Conventional TVM Surgery for Pelvic Organ Prolapse.
- Author
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Kanasaki H, Oride A, Hara T, and Kyo S
- Abstract
Aim: We compared the short-term effectiveness of tension-free vaginal mesh (TVM) surgery using the Capio SLIM suture capturing device and conventional TVM surgery for treatment of pelvic organ prolapse., Methods: We retrospectively compared postoperative pain, urinary function, and length of hospital stay between 7 patients who underwent TVM surgery using the Capio device and 9 patients who underwent conventional TVM surgery., Results: There was no significant between-group difference in mean age between the Capio TVM group and the conventional TVM group (76.0 ± 5.6 years and 72.5 ± 11.5 years) or in mean operating time (86.56 ± 23.33 min and 95.28 ± 23.88 min). Four of the 7 patients in the Capio TVM group could not sense the urge to urinate after removal of the urethral catheter, but all patients in the conventional TVM group did so. The volume of the first voluntary urination was significantly smaller in the Capio TVM group than that in the conventional TVM group (102.14 ± 80.57 mL versus 472.22 ± 459.43 mL). The mean residual urine volume after the first voluntary urination was greater in the Capio TVM group than that in the conventional TVM group (285.70 ± 233.82 mL versus 34.56 ± 73.31 mL). The number of catheter days and mean maximal volume of residual urine were significantly greater in the Capio TVM group. The mean postoperative hospital stay was 6.57 ± 1.83 days in the Capio TVM group and 3.2 ± 0.42 days in the conventional TVM group. Six patients who underwent Capio TVM surgery complained of deep-seated pain in the hip region., Conclusion: Urinary function may worsen postoperatively when the Capio TVM device is used in patients with pelvic organ prolapse. more...
- Published
- 2018
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368. Role of pituitary adenylate cyclase-activating polypeptide in modulating hypothalamic-pituitary system.
- Author
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Oride A, Kanasaki H, and Kyo S
- Abstract
Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional peptide that is isolated and identified from the ovine hypothalamus, whose effects and mechanisms have been elucidated in numerous studies. The PACAP and its receptor are widely expressed, not only in the hypothalamus but also in peripheral organs., Methods: The studies on the role of PACAP in the hypothalamic-pituitary system, including those by the authors, were summarized., Results: In the pituitary gonadotrophs, PACAP increases the gonadotrophin α-, luteinizing hormoneβ-, and follicle-stimulating hormone β-subunit expression and the expression of gonadotropin-releasing hormone (GnRH) receptor and its own receptor, PAC1R. Moreover, a low-frequency GnRH pulse increases the expression of PACAP and PAC1R more than a high-frequency GnRH pulse in the gonadotrophs. The PACAP stimulates prolactin synthesis and secretion and increases PAC1R in the lactotrophs. In the hypothalamus, PACAP increases the expression of the GnRH receptors, although it is unable to increase the expression of GnRH in the GnRH-producing neurons., Conclusion: The PACAP not only acts directly in each hormone-producing cell, it possibly might regulate hormone synthesis via the expression of its own receptors or those of other hormones. more...
- Published
- 2018
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369. Gamma-aminobutyric acid A receptor agonist, muscimol, increases KiSS-1 gene expression in hypothalamic cell models.
- Author
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Kanasaki H, Tumurbaatar T, Oride A, Hara T, Okada H, and Kyo S
- Abstract
Purpose: Accumulating evidence indicates that hypothalamic kisspeptin plays a pivotal role in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis. In this study, the direct action of the gamma-aminobutyric acid (GABA)
A receptor agonist on kisspeptin-expressing neuronal cells was examined., Methods: A hypothalamic cell model of rat hypothalamic cell line R8 (rHypoE8) cells and primary cultures of neuronal cells from fetal rat brains were stimulated with a potent and selective GABAA receptor agonist, muscimol, to determine the expression of the KiSS-1 gene., Results: Stimulation of the rHypoE8 cells with muscimol significantly increased the level of KiSS-1 messenger (m)RNA expression. The ability of muscimol to increase the level of KiSS-1 mRNA also was observed in the primary cultures of the neuronal cells from the fetal rat brains. The muscimol-induced increase in KiSS-1 mRNA expression was completely inhibited in the presence of the GABAA receptor antagonist. Although muscimol increased the expression of KiSS-1, the natural compound, GABA, failed to induce the expression of KiSS-1 in the rHypoE8 cells. Muscimol did not modulate gonadotropin-releasing hormone expression in either the rHypoE8 cells or the primary cultures of the fetal rat brains., Conclusions: This study's observations suggest that the activation of the GABAA receptor modulates the HPG axis by increasing kisspeptin expression in the hypothalamic neurons., Competing Interests: The authors declare no conflict of interest. Human and Animal Rights: This study's protocol was approved by the committee of the Experimental Animal Center for Integrated Research at Shimane University, Izumo, Japan. All the institutional and national guidelines for the care and use of laboratory animals were followed. This article does not contain any study with human participants that has been performed by any of the authors. more...- Published
- 2017
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370. How is GnRH regulated in GnRH-producing neurons? Studies using GT1-7 cells as a GnRH-producing cell model.
- Author
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Kanasaki H, Oride A, Mijiddorj T, Sukhbaatar U, and Kyo S
- Subjects
- Animals, Cell Line, Kisspeptins metabolism, Gonadotropin-Releasing Hormone metabolism, Models, Biological, Neurons metabolism
- Abstract
Hypothalamic secretion of gonadotropin-releasing hormone (GnRH) has been established as a principle pathway for initiating and integrating female reproductive function. GnRH stimulates the release of two gonadotropins-luteinizing hormone and follicle-stimulating hormone-from the anterior pituitary, which eventually stimulate the synthesis of sex steroids in association with follicular growth and ovulation. This reproductive control of the hypothalamic-pituitary-gonadal (HPG) axis also mediates gonadal feedback mechanisms. Although GnRH neurons certainly play a pivotal role in the HPG axis, the detailed mechanisms of their functional network, including regulatory systems, remain unknown. After the discovery of the indispensable role of kisspeptin in the development of human reproductive functions, our understanding of the neuroendocrine regulation of the HPG axis was revolutionized, and it is now recognized that kisspeptin acts upstream of GnRH and is responsible for sex steroid feedback mechanisms. Kisspeptin can stimulate gonadotropin release from the pituitary gland by stimulating GnRH release and GnRH antagonists prevent kisspeptin-induced gonadotropin release. Furthermore, it has been shown that GnRH neurons express kisspeptin receptors. Nevertheless, the detailed mechanisms underlying the regulation of homogeneous populations of GnRH neurons are still largely unknown because of the limitations of experimental models used for investigation. The hypothalamus consists of a complex network of distinct neuronal cells, and it is difficult to isolate single-cell populations of GnRH neurons. The establishment of GnRH-expressing cell lines has allowed us to examine the events happening at the single-cell level. In this review, we describe in vitro studies using a GnRH-producing cell model, GT1-7 cells, which have been used to examine how GnRH-producing cells respond to hypothalamic factors and how they are involved in GnRH synthesis., (Copyright © 2017 Elsevier Inc. All rights reserved.) more...
- Published
- 2017
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371. Expression and Regulation of Pituitary Adenylate Cyclase-Activating Polypeptide in Rat Placental Cells.
- Author
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Oride A, Kanasaki H, Mijiddorj T, Sukhbaatar U, Yamada T, and Kyo S
- Subjects
- Animals, Chorionic Gonadotropin metabolism, Estradiol, Female, Gene Expression Regulation, Gonadotropin-Releasing Hormone administration & dosage, Gonadotropin-Releasing Hormone metabolism, Kisspeptins administration & dosage, Kisspeptins metabolism, Pituitary Adenylate Cyclase-Activating Polypeptide administration & dosage, Pregnancy, Primary Cell Culture, Progesterone, RNA, Messenger metabolism, Rats, Pituitary Adenylate Cyclase-Activating Polypeptide metabolism, Placenta metabolism
- Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) was first identified as a hypophysiotropic factor that regulates pituitary cell functions and has been subsequently shown to be widely distributed and have multiple functions. The PACAP is known to be expressed in placental tissues and is suggested to have a critical role in physiological function of the placenta. In addition to PACAP, the hypothalamic peptides kisspeptin and gonadotropin-releasing hormone (GnRH) are also expressed in placental cells. In this study, we used primary cultures of placental tissues from rats of 16 to 18 days gestation and examined the regulation and function of PACAP. The PACAP messenger RNA (mRNA) expression and PACAP-immunoreactive cells were detected in primary cultures of rat placental cells. The PACAP mRNA expression in placental cells was upregulated in the presence of the sex steroids estradiol and progesterone; however, their combined treatment failed to enhance their individual effects. When the cells were stimulated with kisspeptin, PACAP mRNA expression was increased. Similarly, GnRH had a stimulatory effect on PACAP expression. Conversely, kisspeptin expression in placental cells was increased by PACAP stimulation, whereas PACAP failed to stimulate GnRH mRNA expression in these cells. Finally, we found that PACAP had a stimulatory effect on human chorionic gonadotropin expression in placental cells. Our current observations suggest that the hypothalamic peptides PACAP, kisspeptin, and GnRH are interrelated and maintain placental functions., (© The Author(s) 2016.) more...
- Published
- 2016
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372. Expression of gonadotropin-inhibitory hormone receptors in mouse pituitary gonadotroph LβT2 cells and hypothalamic gonadotropin-releasing hormone-producing GT1-7 cells.
- Author
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Sukhbaatar U, Kanasaki H, Mijiddorj T, Oride A, and Miyazaki K
- Subjects
- Animals, Cell Line, Cyclic AMP-Dependent Protein Kinases genetics, Gene Expression Regulation drug effects, Gonadotropin-Releasing Hormone administration & dosage, Gonadotropin-Releasing Hormone metabolism, Gonadotropin-Releasing Hormone pharmacology, Kisspeptins pharmacology, MAP Kinase Kinase Kinases genetics, Mice, RNA, Messenger analysis, Rats, Receptors, Neuropeptide genetics, Gene Expression drug effects, Gonadotrophs metabolism, Gonadotropin-Releasing Hormone biosynthesis, Hypothalamus metabolism, Receptors, Pituitary Hormone-Regulating Hormone genetics
- Abstract
Gonadotropin-inhibitory hormone (GnIH) was first identified in quail as a novel neurohormone that acts directly on the anterior pituitary to inhibit gonadotropin release. GnIH inhibits not only gonadotropin release from the pituitary gland but also inhibits the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. In this study, we examined how GnIH receptors were regulated in pituitary gonadotroph cells and GnRH-producing neurons in the hypothalamus. In the mouse pituitary gonadotroph cell line LβT2, GnRH increased expression of the GnIH receptor, G-protein coupled receptor 74 (GPR74). GnRH also stimulated the expression of GPR74 and GPR147 in primary cultures of rat anterior pituitary cells. In addition, when GnRH was administered to LβT2 cells in a pulsatile manner, low frequency GnRH pulse stimulation stimulated GPR74 and GPR147 expression more than did high frequency GnRH pulses. In the mouse hypothalamic GnRH-producing cell line GT1-7, hypothalamic kisspeptin did not significantly increase the expression of GnIH receptors. However, the intermittent administration of kisspeptin to GT1-7 cells significantly increased GPR74 and GPR147 mRNA expression. The overexpression of either constitutively active MEK kinase (MEKK) or protein kinase A (PKA) in LβT2 cells increased the expression of GPR74 mRNA. Conversely, in GT1-7 cells, although the overexpression of either MEKK or PKA failed to stimulate GnIH receptor expression, the combined overexpression of both kinases together increased GPR74 and GPR147 mRNA levels. Our current observations suggest that two central controllers of reproductive function, GnRH and kisspeptin, stimulate the expression of GnIH receptors in pituitary gonadotroph cells and hypothalamic GnRH neurons. more...
- Published
- 2014
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373. Effects of estradiol and progesterone on gonadotropin LHβ- and FSHβ-subunit promoter activities in gonadotroph LβT2 cells.
- Author
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Kanasaki H, Purwana IN, Mijiddorj T, Sukhbaatar U, Oride A, and Miyazaki K
- Subjects
- Cell Line, Transformed, Cell Proliferation drug effects, Estradiol pharmacology, Follicle Stimulating Hormone, beta Subunit metabolism, Gene Expression Regulation drug effects, Gene Expression Regulation physiology, Gonadotropin-Releasing Hormone metabolism, Gonadotropin-Releasing Hormone pharmacology, Humans, Luciferases genetics, Luteinizing Hormone, beta Subunit metabolism, Pituitary Gland cytology, Pituitary Gland drug effects, Progesterone pharmacology, Promoter Regions, Genetic physiology, Transfection, Estradiol metabolism, Follicle Stimulating Hormone, beta Subunit genetics, Luteinizing Hormone, beta Subunit genetics, Pituitary Gland physiology, Progesterone metabolism
- Abstract
Objectives: Sex steroid hormones play roles in the regulation of pituitary hormone synthesis and secretion. Here we investigated the role of estradiol (E2) and progesterone (P4) on pituitary gonadotropin luteinizing hormone (LH)β- and follicle stimulating hormone (FSH)β-transcriptional activity in a single colony of gonadotroph LβT2 cells., Methods: Pituitary gonadotroph cell line, LβT2 cells were used in this study. Cells were transfected with LHβ- or FSHβ-subunit promoter region-linked luciferase vector, and stimulated with gonadotropin-releasing hormone (GnRH) in the presence or absence of sex steroids. Transcriptional activity for LHβ- and FSHβ-subunit were determined by luciferase assay. Effects of sex steroids on cell proliferation was also determined by measurement of 5-bromoe-2'-deoxyuridine (BrdU) incorporation., Results: The basal promoter activity of the LHβ subunit was not modulated by 10 nM E2, but gonadotropin releasing hormone (GnRH)-induced LHβ promoter activity was significantly increased by the same concentration of E2. Similarly, although the basal FSHβ promoter was not modulated by 10 nM E2, GnRH-induced FSHβ promoters were significantly potentiated in the presence of E2. One micromole E2 modulated neither basal nor GnRH-induced LHβ and FSHβ promoters. On the other hand, basal LHβ promoter activity was enhanced by 1 µM P4, but the stimulatory response of GnRH on LHβ promoters was significantly inhibited in the presence of 1 µM P4. Similar to LHβ promoters, the basal activity of the FSHβ promoter was increased by 1 µM P4; however, the response to GnRH was not modulated in the presence of P4. Ten micromoles P4 modified neither basal nor GnRH-induced promoter activity for LHβ and FSHβ. E2 had no antagonistic effect on P4-induced basal promoter activities of LHβ or FSHβ. A cell proliferation assay showed that neither E2 nor P4 modulated the growth of LβT2 cells, even in the presence or absence of GnRH., Conclusion: These observations suggest that both E2 and P4 uniquely modulate basal and GnRH-stimulated gonadotropin promoters without affecting cell growth. more...
- Published
- 2012
374. Induction of dual specificity phosphatase 1 (DUSP1) by gonadotropin-releasing hormone (GnRH) and the role for gonadotropin subunit gene expression in mouse pituitary gonadotroph L beta T2 cells.
- Author
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Purwana IN, Kanasaki H, Oride A, and Miyazaki K
- Subjects
- Animals, Butadienes pharmacology, Cell Line, Diterpenes pharmacology, Dual Specificity Phosphatase 1 genetics, Enzyme Activation drug effects, Enzyme Induction drug effects, Enzyme Inhibitors pharmacology, Epoxy Compounds pharmacology, Follicle Stimulating Hormone, beta Subunit genetics, Kinetics, Luteinizing Hormone, beta Subunit genetics, Mice, Mitogen-Activated Protein Kinase 3 antagonists & inhibitors, Mitogen-Activated Protein Kinase 3 metabolism, Nitriles pharmacology, Phenanthrenes pharmacology, Promoter Regions, Genetic genetics, Dual Specificity Phosphatase 1 biosynthesis, Gene Expression drug effects, Gonadotropin-Releasing Hormone pharmacology, Gonadotropins, Pituitary genetics, Pituitary Gland enzymology
- Abstract
We examined the expression of dual specificity phosphatase 1 (DUSP1) by gonadotropin-releasing hormone (GnRH) stimulation and investigated the role of DUSP1 on gonadotropin gene expression using LbetaT2 gonadotroph cell line. DUSP1 expression was markedly increased 60 min after GnRH stimulation, and mitogen-activated protein kinase 3/1 (MAPK3/1) activation was gradually decreased after 60 min. GnRH-induced MAPK3/1 activation was completely inhibited by U0126, a MEK inhibitor, whereas GnRH-induced DUSP1 expression was partially inhibited by U0126. GnRH-induced DUSP1 induction was inhibited by triptolide, a diterpenoid triepoxide. In contrast, this compound potentiated MAPK3/1 activation. U0126 prevented GnRH-stimulated gonadotropin subunit promoter activation dose dependently, and 10 muM of U0126 reduced the effects of GnRH on the Lhb and Fshb promoters to 79.15% and 55.66%, respectively. GnRH-stimulated activation of Lhb and Fshb promoters as well as serum response factor (Srf) promoters were almost completely inhibited by triptolide, suggesting that this component had a nonspecific effect to the cells. Dusp1 siRNA reduced the expression of DUSP1 and augmented MAPK3/1 phosphorylation, but it did not increase of gonadotropin promoters. By overexpression of DUSP1, both GnRH-stimulated Lhb and Fshb promoters were significantly reduced. We have previously shown that insulin-like growth factor 1 (IGF1) increases MAPK3/1 but does not activate gonadotropin subunit promoters. IGF1 failed to induce DUSP1 expression. In addition, under pulsatile GnRH stimulation, DUSP1 expression was observed following high-frequency GnRH pulses but not following low-frequency pulses. Our study demonstrated that DUSP1, induced by GnRH, functions not only as an MAPK3/1-inactivating phosphatase but also as an important mediator in gonadotropin subunit gene expression regulation. more...
- Published
- 2010
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375. [A case of PEP(BEP)-resistant ovarian dysgerminoma successfully treated by VeIP therapy].
- Author
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Ishibashi M, Nakayama K, Oride A, Yeasmin S, Katagiri A, Iida K, Nakayama N, and Miyazaki K
- Subjects
- Adolescent, Bleomycin therapeutic use, Cisplatin therapeutic use, Dysgerminoma blood, Dysgerminoma surgery, Female, Humans, Magnetic Resonance Imaging, Ovarian Neoplasms diagnostic imaging, Ovarian Neoplasms surgery, Positron-Emission Tomography, Remission Induction, Tomography, X-Ray Computed, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Drug Resistance, Neoplasm drug effects, Dysgerminoma drug therapy, Dysgerminoma pathology, Ovarian Neoplasms drug therapy, Ovarian Neoplasms pathology
- Abstract
Ovarian germ cell tumors are malignant tumors which commonly develop during childhood, and which are sensitive to chemotherapy. We have had a case of germ cell tumors which showed resistance to first-line PEP(BEP)chemotherapy. As second-line chemotherapy, VeIP therapy was used, because it is possible that this therapy is effective against recurrent testicular germ cell tumors. The patient was fourteen years old. She experienced acute abdominal pain and visited the hospital, where she was diagnosed with torsion of an ovarian tumor. An emergency laparotomy and right salpingoophorectomy were performed, the pathological diagnosis being stage Ia ovarian dysgerminoma G1. She was followed for two years until her serum hCG-CTP elevated to 1.4 mIU/mL. An MRI revealed an abnormal signal in the left ovary, so we diagnosed this as a recurrence of the dysgerminoma. Then she received chemotherapy PEP(BEP), but after eight months of PEP (BEP), her serum hCG-CTP was again elevated to 14.5 mIU/mL. A recurrence was detected with an MRI and PET-CT, and another laparotomy was performed. The recurrent region was detected in the left ovary. A left ovarian cystectomy was performed in which CDDP ip was used. After the operation, the patient again underwent chemotherapy. VeIP (vinblastine+ifosfamide+cisplatin)was chosen as the second-line regimen. After 6 courses of this therapy, she had a follow-up operation. No recurrence region was found in the pelvic area. She remains without recurrence of this disease 24 months after VeIP therapy. This case suggests that VeIP therapy might be an effective second-line therapy for patients with PEP(BEP)-resistant ovarian dysgerminoma. more...
- Published
- 2009
376. Up-regulation of gonadotropin alpha-subunit gene by phosphatidylinositol 3-kinase inhibitors in clonal gonadotroph cells.
- Author
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Kanasaki H, Mutiara S, Oride A, and Miyazaki K
- Subjects
- Androstadienes pharmacology, Animals, Cells, Cultured, Chromones pharmacology, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases metabolism, Gonadotrophs cytology, Gonadotrophs drug effects, Gonadotropin-Releasing Hormone metabolism, Gonadotropins genetics, Humans, Morpholines pharmacology, Phosphoinositide-3 Kinase Inhibitors, Promoter Regions, Genetic, Protein Kinase Inhibitors pharmacology, Protein Subunits genetics, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Proto-Oncogene Proteins c-akt metabolism, Up-Regulation, Wortmannin, Gonadotrophs physiology, Gonadotropins metabolism, Phosphatidylinositol 3-Kinases metabolism, Protein Subunits metabolism
- Abstract
Objective: Phosphatidylinositol-3 kinase (PI3-kinase) has been known to play an important role in cell survival and proliferation by activation of its downstream target, Akt/protein kinase B (PKB). In this present study, we investigated the effects of PI3-kinase inhibitors on gonadotropin alpha-subunit gene expression in pituitary gonadotrophs., Methods: Alpha T3-1 cells, a pituitary gonadotroph cell line, were used in this study. alphaT3-1 cells were transfected with alpha-subunit promoter region-linked luciferase vector, and stimulated with GnRH in the presence or absence of two different PI3-kinase inhibitors, LY 294002 and wortmannin. Dose response effects of these inhibitors were also examined. Extracellular signal-regulated kinase (ERK) phosphorylation were determined by western blotting analysis., Results: Treatment of alphaT3-1 cells with PI3-kinase inhibitor, LY 294002, significantly increased alpha-subunit gene expression up to 6.89 +/- 0.26-fold, and showed additive effect with gonadotropin-releasing hormone (GnRH). The increasing effect of LY 294002 on alpha-subunit gene expression was observed at the concentration more than 1 microM. The experiment using another PI3-kinase inhibitor, wortmannin, showed similar effects, where wortmannin alone increased alpha-subunit gene expression by dose dependent manner and showed additive effect with GnRH. The inhibitor of PKB failed to modulate basal activity of alpha-subunit promoter as well as GnRH-induced promoter activities. Western blotting analysis using phosphorylated form specific antibody for ERK demonstrated that both LY 294002 and wortmannin increased ERK phosphorylation., Conclusion: These results suggested that PI3-kinase inhibitor, LY 294002 and wortmannin increased gonadotropin alpha-subunit gene expression related with ERK activation. more...
- Published
- 2008
377. The involvement of phosphatidylinositol 3-kinase in gonadotropin-releasing hormone-induced gonadotropin alpha- and FSHbeta-subunit genes expression in clonal gonadotroph LbetaT2 cells.
- Author
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Mutiara S, Kanasaki H, Harada T, Oride A, and Miyazaki K
- Subjects
- Animals, Cell Proliferation drug effects, Clone Cells cytology, Enzyme Activation drug effects, Enzyme Inhibitors pharmacology, Extracellular Signal-Regulated MAP Kinases metabolism, Follicle Stimulating Hormone, beta Subunit metabolism, Glycoprotein Hormones, alpha Subunit metabolism, Gonadotrophs cytology, Gonadotrophs enzymology, Humans, Insulin-Like Growth Factor I pharmacology, Models, Biological, Phosphoinositide-3 Kinase Inhibitors, Phosphorylation drug effects, Promoter Regions, Genetic genetics, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Rats, Time Factors, Follicle Stimulating Hormone, beta Subunit genetics, Gene Expression Regulation drug effects, Glycoprotein Hormones, alpha Subunit genetics, Gonadotrophs drug effects, Gonadotrophs metabolism, Gonadotropin-Releasing Hormone pharmacology, Phosphatidylinositol 3-Kinases metabolism
- Abstract
Akt/protein kinase B (Akt/PKB), which is activated by phosphatidylinositol-3 kinase (PI3-kinase), plays an important role in cell survival and cell proliferation. Using the well differentiated, clonal gonadotroph cell line, LbetaT2, we examined (1) whether Akt/PKB was activated by gonadotropin-releasing hormone (GnRH); (2) the contribution of PI3-kinase-Akt/PKB pathway in each of gonadotropin subunit gene expression; (3) crosstalk between extracellular signal-regulated kinase (ERK) and Akt/PKB pathways. Insulin-like growth factor-1 (IGF-1) was used as Akt/PKBs classic activator. Western blot analyses using antibodies specific for the phosphorylated forms of ERK and Akt/PKB demonstrated that both were rapidly phosphorylated following treatment with GnRH and IGF-1. Akt/PKB activation by GnRH and IGF-1 was completely eliminated in the presence of the PI3-kinase inhibitor, LY 294002, but not in the presence of an Akt/PKB inhibitor. Interestingly, the total amount of Akt/PKB protein was dramatically increased in the presence of LY 294002. Phosphorylation of ERK was significantly increased in the presence of LY 294002 alone, and was further increased when GnRH was used in combination with LY 294002. In experiments using a luciferase reporter construct containing the serum response element (SRE), a known target of the ERK pathway, LY 294002 but not the Akt/PKB inhibitor increased SRE-luciferase activity. GnRH-induced SRE-luciferase activity was significantly increased by LY 294002. GnRH stimulation resulted in gonadotropin LHbeta, FSHbeta, and alpha-subunit promoter activation, while IGF-1 failed to stimulate any of them. GnRH-induced gonadotropin promoter activities were not modulated in the presence of an Akt/PKB inhibitor, but treatment with LY 294002 or Wortmannin resulted in a significant increase in alpha- and FSHbeta-subunit promoter activation, both with and without GnRH. LY 294002, but not the Akt/PKB inhibitor, significantly inhibited cell proliferation. These results suggest that GnRH-induced gonadotropin gene expression is not regulated through the Akt/PKB pathway; however, PI3-kinase may be involved in the negative regulation of alpha- and FSHbeta-subunit gene expression as well as cell proliferation. more...
- Published
- 2008
- Full Text
- View/download PDF
378. A case of extremely chemoresistant pure pleomorphic rhabdomyosarcoma of the uterus associated with a high serum LDH level.
- Author
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Yeasmin S, Nakayama K, Oride A, Ishibashi M, Ishikawa N, Katagiri A, Iida K, Nakayama N, and Miyazaki K
- Subjects
- Drug Resistance, Neoplasm, Female, Humans, Middle Aged, Rhabdomyosarcoma blood, Rhabdomyosarcoma physiopathology, Uterine Neoplasms blood, Uterine Neoplasms physiopathology, L-Lactate Dehydrogenase blood, Rhabdomyosarcoma pathology, Uterine Neoplasms pathology
- Abstract
Background: Pleomorphic rhabdomyosarcoma (RMS) of gynecologic origin is an exceedingly rare, highly malignant tumor. Only a few cases have been reported in the last decades., Case Report: A 60-year-old postmenopausal woman presented with a high LDH level of unknown origin. Ultimately, she was diagnosed with pleomorphic RMS. She underwent total hysterectomy, bilateral salpingo-oophorectomy, left pelvic and paraaortic lymphadenectomy and partial omentectomy. Surgery was followed by systemic chemotherapy and pelvic irradiation. Unfortunately, the patient did not respond to treatment. Her disease course correlated with the fluctuation of plasma LDH levels. Ultimately she died within 20 months of the diagnosis., Conclusion: It is important to have better insight and to set a standard multimodal treatment for adult RMS. In addition, plasma LDH levels can be considered as a prognostic marker for RMS, particularly in advanced stage. more...
- Published
- 2008
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