• BMB Reports
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• v.50 no.9
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• pp.460-465
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• 2017

Polycystic kidney disease (PKD) is one of the most common inherited disorders, involving progressive cyst formation in the kidney that leads to renal failure. FK506 binding protein 12 (FK506BP) is an immunophilin protein that performs multiple functions, including regulation of cell signaling pathways and survival. In this study, we determined the roles of PEP-1-FK506BP on cell proliferation and cyst formation in PKD cells. Purified PEP-1-FK506BP transduced into PKD cells markedly inhibited cell proliferation. Also, PEP-1-FK506BP drastically inhibited the expression levels of p-Akt, p-p70S6K, p-mTOR, and p-ERK in PKD cells. In a 3D-culture system, PEP-1-FK506BP significantly reduced cyst formation. Furthermore, the combined effects of rapamycin and PEP-1-FK506BP on cyst formation were markedly higher than the effects of individual treatments. These results suggest that PEP-1-FK506BP delayed cyst formation and could be a new therapeutic strategy for renal cyst formation in PKD.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.1
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• pp.33-39
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• 2017

Objective: The aim of this study was to assess the changes of follicular fluid (FF) and serum levels of cerebellin precursor protein 1 (cbln1) and betatrophin in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with a gonadotropin-releasing hormone (GnRH) antagonist protocol. Methods: Twenty infertile women with PCOS and 20 control women diagnosed as poor responders undergoing ovarian stimulation with a GnRH antagonist were included. Blood samples were obtained during ovum pick-up. Follicular fluid from a dominant follicle was collected from the subjects. Using enzyme-linked immunosorbent assays, FF and serum levels of cbln1 and betatrophin were measured in both groups of participants. Metabolic and hormonal parameters were also determined and correlated with each other. Results: Both groups of women had similar serum and FF betatrophin levels ($55.0{\pm}8.9ng/mL$ vs. $53.1{\pm}10.3ng/mL$, p=0.11). The serum and FF betatrophin levels of poor responders were found to be similar ($49.9{\pm}5.9ng/mL$ vs. $48.9{\pm}10.7ng/mL$, p=0.22). Conversely, the FF cbln1 levels of PCOS women were found to be significantly higher than the serum cbln1 levels ($589.1{\pm}147.6ng/L$ vs. $531.7{\pm}74.3ng/L$, p<0.02). The FF cbln1 levels of control participants without PCOS were significantly higher than their serum cbln1 levels ($599.3{\pm}211.5ng/L$ vs. $525.3{\pm}87.0ng/L$, p=0.01). Positive correlations were detected among body mass index, insulin resistance, serum insulin, total testosterone, and betatrophin levels in the PCOS group. Conclusion: Follicular fluid betatrophin and cbln1 concentrations may play a pivotal role on follicular growth in PCOS subjects undergoing IVF/ICSI with an antagonist protocol.

• The Journal of the Korean life insurance medical association
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• v.3 no.1
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• pp.187-208
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• 1986

The conclusions which was acquired one renal cell carcinoma and renal disease 132 cases that was tested renal echogram among 4,499 cases for recent 16 months at medical department, Dae Han Kyoyuk Insurance company from August, 1984 to November, 1985 are as follows: 1. On bur ultrasonography, the echo of tumor was demonstrated with echogenicity as compared with renal parenchyme. 2. The case was stage I by Robson's modification method for pathologic histology. 3. There is no fever, typical triad of renal cell carcinoma and the result of serum biochemical test was within normal limit. 4. The frequency with disease was renal cell carcinoma(0.76%), ureteral stone(1.5%), multicystic kidney(2.27%), hydroureter(2.27%), Bilateral poly cystic kidney(4.55%), hydronephrosis(4.55%), renal agenesis(6.06%) renal calculi(18.18%), simple cyst(60.61%). 5. The frequency with age was 55/1200 case(4.58%) in $41{\sim}50$ years, 13/296 cases(4.39%) in $51{\sim}60$ years, 43/2144 cases(2.01%) in $31{\sim}40$ years, 14/791 cases(1.77%) in $21{\sim}30$ years, 7/53 cases(1.32%) more than 61 years and 0/15(0%) under 20 years. 6. The affected site of renal agenesis 8 cases was right side all. 7. In total renal disease 132 cases, the affected site of 126 cases except bilateral polycystic kidney 6 cases was right kidney 72 cases, left kidney the proportion of right to left 1.6:1 8. In total renal disease 132 cases except bilateral polycystic kidneys 6 cases, the patients affected with both side kidneys were 14 cases. 9. The affection rate with sex in total renal disease 132 cases was 98/2860 cases in male, 34/1819 cases in female and the former was about 2 times than the latter. 10. Classifying the stone with part, nephrolithiasis 24 cases were appeared high frequency, on the contray, ureteral stone 2 cases. 11. 2 cases of ureteral stone developed complication, hydronephrosis and hydroureter. 12. The linear array type transducer was not helpful for the diagnosis of lower ureteral calculi but for the lower ureteral calculi, we could see the stone with high echo in accompanying with acoustic shadowing. 13. In 24 cases of renal calculi, both side nephrolithiasis was 3 cases(12.5%). 14. In renal calculi, solitary stone could be seen extremely much and the number of stone was so much variable from 2 to 10. 15. In 26 cases with renal calculi and ureteral stone, the common clinical manifestation was a intermittent and slight pain. 16. In 80 cases of renal cyst, as one's get older, the affection rate of cyst extremely rised. 17. In bilateral polycystic kidney, large cyst had septum on the whole. 18. The patients with complication were 14 cases(10.6%) of total patients.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.2
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• pp.141-151
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• 1998

Objectives: To determine whether the body weight, body mass index (BMI), and basal serum level of LH, FSH, testosterone (T), dehydroepiandrosterone sulfate (DHEA-S) are related to the ovarian response to clomiphene citrate (CC) in patients with polycystic ovarian syndrome (PCOS). Materials and Method: From January 1996 to June 1997, total 57 patients with PCOS were enrolled in the present study. Women who had other infertility factors were excluded from our study. The ovulation induction using CC was used in all patients. The patients were grouped into 50 mg group, 100 mg group, and 150 mg group according to their daily CC dose. The patients were also grouped to ovulatory and non-ovulatory group. The body weight, BMI, and basal serum level of LH, FSH, T, DHEA-S were measured in all patients on the 2nd or 3rd day of the menstrual cycle. Results were analysed with Student's t-test and Fisher's exact test. Results: The body weight and BMI of the nonovulating group were significantly higher than those of the ovulating group in all groups (50, 100, 150 mg of CC). However, there were no significant differences of the level of LH and FSH between ovulating and nonovulating groups in all CC groups (50, 100, 150 mg). The level of T of nonovulating group was significantly higher in 50 and 100 mg of CC groups, but not in 150 mg group. The level of DHEA-S of the non-ovulating group is significantly higher in 50 mg group, but not in 100 and 150 mg groups. Conclusion: The body weight and BMI could be useful predictors of ovarian response to CC in patients with PCOS, and basal T and DHEA-S also might be useful in cases of low-dose CC treatment.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.2
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• pp.82-89
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• 2016

Objective: The long interspersed elements (LINE-1, L1s) are a group of genetic elements found in large numbers in the human genome that can translate into phenotype by controlling genes. Growing evidence supports the role of epigenetic in polycystic ovary syndrome (PCOS). The purpose of this study is to evaluate the DNA methylation levels in LINE-1 in a tissue-specific manner using cumulus cells from patients with PCOS compared with normal controls. Methods: The study included 19 patients with PCOS and 22 control patients who were undergoing controlled ovarian hyperstimulation. After oocyte retrieval, cumulus cells were extracted. LINE-1 DNA methylation levels were analysed by bisulfite treatment, polymerase chain reaction, and restriction enzyme digestion. The Connection Up- and Down-Regulation Expression Analysis of Microarrays software package was used to compare the gene regulatory functions of intragenic LINE-1. Results: The results showed higher LINE-1 DNA methylation levels in the cumulus cells of mature oocytes in PCOS patients, 79.14 (${\pm}2.66$) vs. 75.40 (${\pm}4.92$); p=0.004, but no difference in the methylation of cumulus cells in immature oocytes between PCOS and control patients, 70.33 (${\pm}4.79$) vs. 67.79 (${\pm}5.17$); p=0.155. However, LINE-1 DNA methylation levels were found to be higher in the cumulus cells of mature oocytes than in those of immature oocytes in both PCOS and control patients. Conclusion: These findings suggest that the epigenetic modification of LINE-1 DNA may play a role in regulating multiple gene expression that affects the pathophysiology and development of mature oocytes in PCOS.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.2
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• pp.126-132
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• 2016

Objective: The purpose of this study was to identify useful clinical factors for the identification of patients with polycystic ovary syndrome (PCOS) who would benefit from in vitro maturation (IVM) treatment without exhibiting compromised pregnancy outcomes. Methods: A retrospective cohort study was performed of 186 consecutive patients with PCOS who underwent human chorionic gonadotropin-primed IVM treatment between March 2010 and March 2014. Only the first IVM cycle of each patient was included in this study. A retrospective case-control study was subsequently conducted to compare pregnancy outcomes between IVM and conventional in vitro fertilization (IVF) cycles. Results: Through logistic regression analyses, we arrived at the novel finding that serum $anti-M{\ddot{u}}llerian$ hormone (AMH) levels and the number of fertilized oocytes in IVM were independent predictive factors for live birth with unstandardized coefficients of 0.078 (95% confidence interval [CI], 1.005-1.164; p=0.037) and 0.113 (95% CI, 1.038-1.208; p=0.003), respectively. Furthermore, these two parameters were able to discriminate patients who experienced live births from non-pregnant IVM patients using cut-off levels of 8.5 ng/mL and five fertilized oocytes, respectively. A subsequent retrospective case-control study of patients with PCOS who had serum AMH levels ${\geq}8.5ng/mL$ showed that IVM had pregnancy outcomes comparable to conventional IVF, and that no cases of ovarian hyperstimulation syndrome were observed. Conclusion: Serum AMH levels are a useful factor for predicting pregnancy outcomes in PCOS patients before the beginning of an IVM cycle. IVM may be an alternative to conventional IVF for PCOS patients if the patients are properly selected according to predictive factors such as serum AMH levels.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.2
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• pp.100-105
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• 2013

Objective: The aim of this study was to investigate the effect of insulin sensitizing agents on hormonal and metabolic parameters as well as menstrual patterns in women with polycystic ovary syndrome (PCOS). Methods: One hundred and twenty-three patients with PCOS were included. Metformin was administered to patients at 1,500 mg or 1,700 mg daily for 3 months. If the patients had no improvement of the menstrual cycle or metformin-related adverse effects developed, the patients changed medication to a daily dose of either 15 mg pioglitazone or up to 45 mg. Then resumption of a regular menstrual cycle or recovery of ovulation was evaluated. Hormonal and metabolic profiles were compared between the response and non-response group to insulin sensitizing agents. Results: One hundred and five patients with PCOS were treated with metformin for 3 months. Forty-eight patients (45.7%) showed improvement of menstrual cycle regularity after 3 months of metformin use, whereas 57 patients (54.3%) had no change. The mean free testosterone measured after 3 months of treatment was significantly lower in metformin responders than in non-responders. The other parameters did not differ between the groups. Of the 23 patients who used pioglitazone for 3 to 6 months, 19 patients (82.6%) showed improvement in their menstrual cycles. Conclusion: Metformin treatment seems to be effective for the improvement of menstrual cyclicity irrespective of insulin resistance in women with PCOS. When metformin related adverse effect occurred, pioglitazone would be effective for aiding the resumption of the menstrual cycle.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.1
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• pp.93-102
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• 1998

Normal and abnormal follicular growth and steroidogenesis depend on gonadotropins as well as intraovarian peptides, which may mediate or potentiate gonadotropin action. Inhibin also affect follicular development and steroidogenesis and may play a role in dominant follicle selection and follicular atresia. Therefore, we studied the differences of serum inhibin, gonadotropin and androgen levels in the women with only the ultrasound findings and no disorder, and polycystic ovary (PCO) with ovulatory disturbance. We prospectively analysed forty-three women with PCO. The diagnosis of PCO was based on typical appearance of the ovaries on TVS. Twelve women with regular menstrual cycle and normal ovarian morphology were selected as control. Basal levels of inhibin, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol $(E_2)$, testosterone (T), androstenedione (ADD), dehydroepiandrosterone-sulfate (DS), prolactin and TSH in serum were determined. There were significant differences in basal LH levels and LH/FSH ratio between the control and the women with PCO. The basal levels of inhibin and $E_2$ in the oligo-amenorrheic PCO (N=34) were significantly higher than those in the control. There was higher negative correlation between the inhibin and T levels in the oligo-amenorrheic PCO, but, not in the regular cycling PCO. Also, there was higher positive correlation between the LH and T levels in the oligo-amenorrheic PCO, but not in the regular cycling PCO. These data presume that the initial event of PCO is elevated pituitary LH secretion. Elevated levels of LH may down-regulate LH receptors on granulosa cells and also cause hypertrophy of the thecal layer. High level of androgen secreted by the hypertrophied thecal layer may stimulate inhibin secretion from granulosa cells and can be converted to estrogen by extraovarian tissues and could serve to augment pituitary sensitivity to GnRH with a resultant secretion of more LH than FSH. Inhibin may inhibit FSH action on granulosa cell in the PCO follicle, impairing follicular development and dominant follicle selection resulted in ovulatory disturbance.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.3
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• pp.483-490
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• 1999

Objectives: Polycystic ovary syndrome (PCOS) has the feature of excessive LH, hyperandrogenism and disturbance of folliculogenesis. Also, insulin, IGF-I and IGFBP-l are involved in the pathogenesis of PCOS. Various surgical and medical therapies have been used and the action mechanisms are related to the endocrine effect. Laparoscopic ovarian electrocautery or laser vaporization is effective in the restoration of ovulation and normal menstrual cycle with minimal invasive procedure especially in the patients resistant to medical therapy. Clomiphen citrate (CC) is used for the ovulation induction in pcas and the resistance is known to be related to insulin, IGF-I, IGFBP-l levels. This study was performed to evaluate the effect of the laparoscopic laser vaporization on the levels of LH, FSH, testosterone, IGF-I and IGFBP-l and on the ovarian response to clomiphen citrate in patients with CC-resistant PCOS. Materials and Methods: The fasting basal serum LH, FSH, testosterone, IGF-I and IGFBP-l level were measured in 10 PCOS patients with CC-resistance and 7 normal controls with regular menstrual cycle. In PCOS, after laparoscopic $CO_2$ laser vaporization, endocrine levels were measured in 1 week interval for 4 weeks and then compared with preoperative levels. Results: In PCOS group, mean serum LH/FSH ratio, testosterone, IGF-I levels were higher and IGFBP-l level was lower than control. LH/FSH ratio decreased from $2.51{\pm}0.67$ to $1.7{\pm}0.6$ (p<0.05) in 2 weeks, to $0.56{\pm}0.2$ (p<0.01) in 3 weeks and to $1.41{\pm}0.3$ (p<0.01) in 4 weeks after operation. Testosterone level decreased from $1.51{\pm}0.82ng/ml$ to $0.65{\pm}0.34ng/ml$ (p<0.05) in 2 weeks, to $0.56{\pm}0.67ng/ml $(p<0.01) in 3 weeks after operation. IGF-I level also decreased from $436{\pm}47.5{\mu}g/l$ to $187{\pm}38{\mu}g/l$ (p<0.0l) in 1 week, to $167{\pm}42{\mu}g/l$ (p<0.01) in 2 weeks, $179{\pm}55{\mu}g/l$ (p<0.01) in 3 weeks and to $120{\pm}43{\mu}g/l$ (p<0.01) in 4 weeks after operation. IGFBP-l level showed no significant change. In 8 of 10 PCOS patients, ovulation was induced with low dose clomiphen citrate. Conclusion: Laparoscopic $CO_2$ laser vaporization restores normal menstrual cycle and ovulation through endocrine effect of decreasing LH/FSH ratio, testosterone and IGF-I level and increases the response to CC. Therefore it is useful for restoration of normal menstruation and induction of ovulation in CC resistant PCOS patients.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.2
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• pp.103-108
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• 2011

Objective: To investigate adverse pregnancy outcomes in non-obese women with polycystic ovary syndrome (PCOS) compared with obese-PCOS and control groups. Methods: Women with PCOS who underwent assisted reproductive technology (ART) from August, 2003 to December, 2007, were considered. A total of 336 women with PCOS were included in the study group and 1,003 infertile women who had tubal factor as an indication for ART were collected as controls. They were divided into four groups: a non-obese PCOS group, obese-PCOS group, non-obese tubal factor group, and obese tubal factor group, with obesity defined by a body mass index over 25 kg/$m^2$, and reviewed focusing on the basal characteristics, ART outcomes, and adverse pregnancy outcomes. Results: There was no difference among the groups' the clinical pregnancy rate or live birth rate. Regarding adverse pregnancy outcomes, the miscarriage rate, multiple pregnancy rate, and prevalence of preterm delivery and pregnancy induced hypertension were not different among the four groups. The incidence of small for gestational age infant was higher in the PCOS groups than the tubal factor groups ($p$ <0.02). On the other hand, the morbidity of gestational diabetes mellitus (GDM) was not high in the non-obese PCOS group but was in the obese groups. And in the obese PCOS group, the newborns were heavier than in the other groups ($p$ <0.02). Conclusion: Non-obese PCOS presents many differences compared with obese PCOS, not only in the IVF-parameters but also in the morbidity of adverse pregnancy outcomes, especially in GDM and fetal macrosomia.