• Clinical and Experimental Reproductive Medicine
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• v.47 no.3
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• pp.194-206
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• 2020

Objective: The aim of this study was to investigate microRNAs (miRNAs) related to follicle-stimulating hormone (FSH) responsiveness using miRNA microarrays and to identify their target genes to determine the molecular regulatory pathways involved in FSH signaling in KGN cells. Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis. Potential target genes of selected miRNAs were predicted using bioinformatics tools, and their regulatory function was confirmed in KGN cells. Results: We found that six miRNAs (miR-1261, miR-130a-3p, miR-329-3p, miR-185-5p, miR-144-5p and miR-4463) were differentially expressed after FSHR siRNA treatment in KGN cells. Through a bioinformatics analysis, we showed that these miRNAs were predicted to regulate a large number of genes, which we narrowed down to cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and estrogen receptor alpha (ESR1) as the main targets for miR-4463. Functional analysis revealed that miR-4463 is a regulatory factor for aromatase expression and function in KGN cells. Conclusion: In this study, we identified differentially expressed miRNAs related to FSH responsiveness. In particular, upregulation of miR-4463 expression by FSHR deficiency in human granulosa cells impaired 17β-estradiol synthesis by targeting CYP19A1 and ESR1. Therefore, our data might provide novel candidates for molecular biomarkers for use in research into poor responders.

• Proceedings of the KSAR Conference
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• 2004.06a
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• pp.214-214
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• 2004

Follicle stimulating hormone (FSH) is a pituitary glycoprotein composed of two post translationally modified subunits, which must properly assemble to be biologically active. We developed a transgenic (TG) mouse model that overexpresses the human Follicle-Stimulating hormone (FSH) -subunit under the bovine -casein promoter, displaying in females an excessive levels express in mammary gland. (omitted)

• Clinical and Experimental Reproductive Medicine
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• v.15 no.2
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• pp.135-147
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• 1988

To compare the stimulation effect of the ratio in follicle stimulating hormone and luteinizing hormone in induction of multiple follicular growth, the serum $E_2$ level, the diameter of follicle, number of aspirated follicles and cleavage rate of in vitro fertilized preovulatory oocytes as well as the pregnancy rate were evaluated. Forty one patients with irreparable tubal disease were stimulated by hMG(n=24) or FSH/hMG(n=17) for the purpose of in vitro fertilization and embryo transfer. The following results were obtained. 1. Serum estradiol($E_2$) levels on the day of hCG administration were $921.0{\pm}353.3\;pg/ml$ in hMG group and $1272.9{\pm}1060.6\;pg/ml$ in FSH/hMG group. The serum $E_2$ value of hMG group was significantly lower than that of FSH/hMG group. 2. The diameter of leading follicle by ultrasonogram on the day of hCG administration were $16.2{\pm}2.0\;mm$ in hMG group and $16.2{\pm}2.6\;mm$ in FSH/hMG group. No significant difference of follicle diameter between two groups was demonstrated. 3. The number of follicles with diameter above 10 mm by sonogram on the day of hCG injection were $3.91{\pm}2.32$ in hMG group and $6.52{\pm}3.86$ in FSH/hMG group. There was significant difference of number of follicles between two groups, (p< 0.01). 4. The number of oocytes found per patient at aspiration were $2.59{\pm}1.00$ in hMG group and 3. $76{\pm}2.31$ in FSH/hMG group. There was significant difference of number of aspirated oocytes between two groups. (p< 0.05). 5. The detection rate of preovulatory oocyte at aspiration were 68.4%(39/57) in hMG group (n=22) and 77.6%(38/49) in FSH/hMG group (n=13). 6. The cleavage rate of preovulatory oocyte at 44 hours after insemination were 74.4%(29/39) in hMG group(n=22) and 81.6%(31/38) in FSH/hMG group (n=13). When only hMG was used, one pregnancy was established in 15 patients to whom 29 zygotes were transferred. And a full term normal female baby was delivered by elective cesarean section. In the FSH/hMG group, five pregnancies out of 9 transferred patients were confirmed by serum ${\beta}-hCG$. Two pregnancies were spontaneously aborted before the 6th week of pregnancy. One patient aborted her baby at the 18th week of pregnancy because of incompetent internal os of the cervix. Two patients delivered two full term babies by elective cesarean section. From the above findings, paralell with the increase in the ratio of exogenous follicle stimulating hormone to luteinizing hormone, an increase in oocyte recovery was observed as well as an improvements in pregnancy rate. It was concluded that FSH enrichment early in the follicular phase had a beneficial effect in the controlled ovarian hyperstimulation.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.3
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• pp.281-286
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• 1998

Premature ovarian failure is a condition causing amenorrhea, hypoestrogenism, and elevated gonadotropins in women younger than 40 years. Many causes of premature ovarian failure were reported, including genetic abnormalities, enzymatic defects, defects in gonadotropin secretion or action, autoimmune disorders, physical and idiopathic causes. Recently, Finnish group reported a point mutation in the follicle stimulating hormone (FSH) receptor gene in premature ovarian failure patients. But it was reported that the group from United States could not find any mutation in FSH receptor gene. So we analysed C566T point mutation of FSH receptor gene using restriction fragment length polymorphism (RFLP) and compared the result between premature ovarian failure patient with idiopathic and known causes. But we did not find 556C${\rightarrow}$T mutation in the FSH receptor gene in both groups. These findings suggest that the missense mutation in the human FSH receptor gene reported in Finnish women with premature ovarian failure is uncommon in Korean women with premature ovarian failure.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2006.10a
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• pp.110-110
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• 2006

• Clinical and Experimental Reproductive Medicine
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• v.16 no.1
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• pp.69-79
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• 1989

Steroid hormone profiles during luteal phase of clomiphene citrate(CC)/human menopausal gonadotropin(hMG)/human chorionic gonadotropin(hCG)-stimulated in vitro fertilization (IVF) cycles and of follicle-stimulating hormone(FSH)/hMG/hCG-stimulated IVF cycles were compared. In seventy three cycles stimulated with CC/hMG/hCG regimen, follicles were aspirated during exploratory laparotomy and yielded 7 pregnancies, and in 83 cycles stimulated with FSH/hMG/hCG regimen, follicles were aspirated by laparoscope and made 13 pregnancies. Serum estradiol($E_2$) and progesterone($P_4$) levels were determined on days 2, 5, 7, and 9 after follicle aspiration. The FSH/hMG/hCG regimen was more effective than the CC/hMG/hCG regimen in folliculogenesis, ie, ovarian stimulation, follicular phase $E_2$ peak levels, oocyte maturation, and the number of retrieved oocytes. There was no significant difference between luteal serum $P_4/E_2$ ratio of the two regimens, suggesting that secretory endometrial build-up ability for implantation may not differ each other. Several significant correlations were observed between follicular phase seum $E_2$ peak levels and luteal phase serum $E_2$ and $P_4$ levels in the FSH/hMG/hCG-stimulated cycles but any correlation was not significant in the CC/hMG/hCG-stimulated cycles, suggesting that somewhat more follicles may eventually fall in atresia even after attaining dominant stage in the CC/hMG/hCG-stimulated cycles than the FSH/hMG/hCG-stimulated cycles.

• Clinical and Experimental Reproductive Medicine
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• v.20 no.2
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• pp.125-130
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• 1993

Polycystic ovarian syndrome (PCOS) patients have a characteristic of high leuteinizing hormone (LH) to follicle -stimulating hormone (FSH) ratio. Usually, human menopausal gonadotropin (hMG) is used to induce ovulation in clomiphene citrate-resistant PCOS patients. However, HMG contains two components, namely, LH and FSH, with 50%, respectively. Therefore, FSH is theoretically recommended to stimulate follicular maturation. From the pituitary, LH is secreted by pulsatile pattern. So, we have been using intermittent subcutaneous injection of pure FSH for ovulation induction in 10 PCOS patients from March, 1990 to August, 1992. We obtained good results by intermittent subcutaneous injection of pure FSH. Ovulation is 100% per patient, and 88.2% per cycle. Pregnancy rate is 80% per patient, and 23.5% per cycle. Ovarian hyperstimulation syndrome (OHSS) is 50% per patient, 41.2% per all cycles, and 46.7% per all ovulated cycles. In comparison with HMG, pregnancy rate per cycle is relatively low. But, ovulation rate and pregnacy rate per person is higher than HMG. Because of the strict check of ovaries by the vaginal ultrasonography, OHSS rate is relatively high.

• Clinical and Experimental Reproductive Medicine
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• v.27 no.1
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• pp.15-22
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• 2000

Objective: To elucidate the location of leptin and receptors of ovary specimens obtained from patients undergoing hysterectomy by immunohistochemical staining and to determine the effect of leptin on the steroidogenesis of cultured granulosa cells. Method: In the culturing process of the granulosa cells, FSH (1 IU/ml)and leptin (50 ng/ml), IGF-I (50 ng/ml) was administered to each study group (Group I: FSH; Group II: FSH, leptin; Group III: FSH, IGF-I; Group IV: FSH, IGF-I, leptin), and the levels of estradiol, progesterone, androstenedione in the culture media was measured by radioimmunoassay. Statistical analysis was conducted by one-way ANOVA with Scheffe test. Results: The results showed that leptin and leptin receptors were both found to be strongly stained in granulosa and theca cells, and also in some interstitial cells. Leptin receptors were also observed in cultured granulosa cells. While there was no statistically significant difference in the androstnedione concentrations between the groups, estradiol concentrations was significantly decreased in Group IV ($2202.0{\pm}151.14$ pg/ml) compared to Group III ($2859.0{\pm}122.6$ pg/ml), and progesterone concentrations were also significantly decreased in Group II($4696.3{\pm}190.6$ ng/ml) and Group IV ($4517{\pm}206.78$ ng/ml) compared to Group III($5546.0{\pm}179.5$ ng/ml). Conclustion: The study result of this study suggest that leptin is directly involved in the regulation of ovarian functions, in particular steroidogenesis.

• Fisheries and Aquatic Sciences
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• v.25 no.1
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• pp.12-19
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• 2022

In the present study, we investigated the effects of recombinant eel gonadotropins (rec-GTHs) on maturation induction in immature ovarian culture in vitro and sex steroid hormones in vivo in the Japanese eel Anguilla japonica. To study the in vitro effects of rec-GTHs on estradiol-17β (E2) production in immature ovarian tissues, ovarian tissues were incubated with different doses of rec-follicle-stimulating hormone (rec-FSH) or rec-luteinizing hormone (rec-LH). The results revealed that the E2 levels in the rec-FSH (0.1, 0.5, or 1 ㎍/mL)- and rec-LH (0.1 or 0.5 ㎍/mL)-treated groups were significantly higher than those in the female eels from the control group. Furthermore, to investigate the in vivo effects of rec-GTHs on the gonadosomatic index (GSI) and plasma sex steroid hormone levels, the eels were injected intraperitoneally with eel's ringer (control), salmon pituitary extract (SPE; for female eels), human chorionic gonadotropin (hCG; for male eels), rec-FSH, rec-LH, and rec-FSH + rec-LH once a week. The results revealed that except for the SPE and the hCG groups, none of the groups exhibited a significant difference in GSI values. However, in vivo plasma E2 levels increased at the end of 4 weeks after rec-FSH treatment in female eels. Based on these results, it is suggested that rec-GTHs may have a positive effect on sexual maturation in female eels; however, further studies on complementary rec-protein production systems and additional glycosylation of rec-hormones are needed to elucidate hormone bioactivity in vivo and in vitro.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.3
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• pp.219-224
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• 2009

Objective: Hypogonadotropic hypogonadism (HH) is an uncommon cause of male infertility. We investigated the outcome of gonadotropin therapy for restoring fertility and pregnancy outcomes in patients with HH. Methods: Medical charts of 10 infertile male patients with HH treated with gonadotropin were reviewed. Initial testicular volume were estimated. Semen analysis parameters (semen volume, sperm counts, motility), serum leutenizing hormone (LH), follicle stimulating hormone (FSH), total testosterone were determined before and after human chorionic gonadotropin/human menopausal gonadotropin (hCG/hMG) treatment. Differences were analyzed statistically. Results: Of 10 patients, 7 (70%) succeed at pregnancy (nature pregnancy in 4). Semen analysis parameters, serum FSH, and testosterone were increased significantly after treatment. The population was stratified according to initial testicular volume into a small testis subset (testicular volume less than 10 cc in 4) and a large testis subset (testicular volume 10 cc or greater in 6). Semen analysis parameters and serum testosterone were increased significantly after treatment in large testis subset. Conclusion: Infertile men with HH initiate and maintain spermatogenesis with gonadotropin (hCG/hMG alone or combined) therapy, thus gonadotropin therapy is good choice in infertile men with HH.