Carotenoid components and their biosynthesis in a bud mutant of Shiranui mandarin (Citrus reticulata Blanco) with citrine flavedo / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Carotenoids are secondary metabolite responsible for colored pigments in plants and microbes (Li et al., 2022). They are a class of C40 tetraterpenoids consisting of eight isoprenoid units, and can be classified into carotenes and xanthophylls on the basis of their functional groups (Saini et al., 2015). Carotenes can be linear (phytoene, phytofluene, and ζ‍-carotene) or branched (β‍-carotene and α‍-carotene). Xanthophylls comprise β,β‍-xanthophylls (β‍-cryptoxanthin, zeaxanthin, violaxanthins, and neoxanthin) and β,ε‍-xanthophylls (α-cryptoxanthin, α-carotene, and lutein). Citrus fruits are complex sources of carotenoids, which are the principal pigments responsible for the typical orange color of most types (Chen, 2020). The difference in total carotenoid content and the diversity of carotenoid isomer proportion also accounts for other colors of citrus fruits, such as yellow, red, and pink (Chen, 2020).

A randomized controlled trial on the effect of Lutein Supplementation on Macular Pigment Optical Density and Macular Function in Pseudophakic Patients

Objective@#To evaluate the efficacy of oral lutein supplementation on macular pigment optical density (MPOD) levels and macular function in pseudophakic eyes that underwent phacoemulsification. @*Methods@#This was a prospective, randomized, parallel-arm, single-masked study comparing oral lutein supplement 20 mg/tablet (Lutax 20) with non-supplementation in pseudophakic eyes. We assessed MPOD, low-luminance deficit (LLD), visual recovery time (VRT) using photostress test, and adverse events. One hundred twenty-eight (128) eyes were enrolled and randomized 1:1 to active treatment (lutein supplementation) or no treatment (no supplementation). The supplementation period was 12 weeks and patients were assessed every 4 weeks over a period of 16 weeks.@*Results@#Sixty-four (64) eyes in each group completed the study. A significant increase in MPOD (p<0.001) was observed in the lutein supplemented group, from 0.36 DU at baseline to 0.55 DU at week 12, with a mean increase of 6.32 ± 1.72% per 4 weeks of supplementation compared with a mean MPOD decrease rate of 0.63 ± 0.48% in the non-supplementation group. A significant reduction in LLD was observed in the lutein-treated group, from LogMAR 0.063 at baseline to LogMAR 0.023 at Week 12 (p=0.003). VRT was also significantly shorter in the treatment from a baseline of 83.06 to 68.80 seconds at Week 12 (p<0.001).@*Conclusion@#Lutein supplementation (20 mg/tablet; Lutax 20) demonstrated a significant degree of MPOD augmentation, and reductions in LLD and VRT among patients who underwent phacoemulsification with lens implantation.

Durable Response of Androgen Receptor-Positive Male Breast Cancer to Goserelin / 한국유방암학회지

The luteinizing hormone-releasing hormone/androgen receptor (LHRH/AR) pathway is a promising treatment target in a subgroup of female patients with triple-negative breast cancer (TNBC). However, very little is known about the efficacy of this strategy in male patients with TNBC. In this report, we describe a male patient with AR-positive TNBC who was successfully treated using an LHRH agonist after pretreatment with several lines of chemotherapy and achieved a durable response. We also review the existing evidence supporting LHRH- and AR-targeted therapy for this rare disease.

Dietary Antioxidant Intake in Relation to Semen Quality Parameters in Infertile Men: a Cross-Sectional Study

The objective of this study was to assess the association between dietary antioxidant intake and semen quality parameters in infertile men. In this cross-sectional study, dietary antioxidant intake was evaluated in 175 infertile Iranian men by a validated dish-based 106-item semi-quantitative food frequency questionnaire. Men were asked to abstain from ejaculation for at least 72 hours before sample collection. Semen parameters were assessed by a sperm counting chamber and Terminal deoxynucleotidyl transferase dUTP nick end labeling assay methods. Linear quantile regression was used to determine the associations between antioxidant nutrient intake and semen quality parameters (including total sperm count, sperm density, total motility, DNA damage and DNA fragmentation). Mean age of study participants was 32.19 ± 2.34 years. Compared with the lowest quartile, men in the highest quartile of dietary β-carotene and vitamin C intake had lower sperm DNA fragmentation index (Ptrend = 0.042 and Ptrend = 0.03, respectively). Also, dietary intake of beta-cryptoxanthin had a positive association with sperm density (Ptrend = 0.02), and dietary lutein was associated with total sperm count (P(trend) = 0.045). Dietary intake of other antioxidants did not significantly correlate with the indicators related to the quantity and quality of sperm (p > 0.05). These data suggest that dietary intake of some of the antioxidants is associated with semen related parameters.

Basal serum luteinizing hormone value as the screening biomarker in female central precocious puberty

PURPOSE: Precocious puberty refers to the development of secondary sex characteristics before ages 8 and 9 years in girls and boys, respectively. Central precocious puberty (CPP) is caused by premature activation of the hypothalamus-pituitary-gonadal (HPG) axis and causes thelarche in girls before the age of 8. A gonadotropin-releasing hormone (GnRH) stimulation test is the standard diagnostic modality for diagnosing CPP. However, the test cannot always be used for screening because it is expensive and time-consuming. This study aimed to find alternative reliable screening parameters to identify HPG axis activation in girls <8 years old (CPP) and for girls 8–9 years old (early puberty, EP). METHODS: From January 2013 to June 2015, medical records from 196 girls younger than 9 years old with onset of breast development were reviewed, including 126 girls who had a bone age (BA) 1 year above their chronological age. All patients underwent a GnRH stimulation test, and 117 underwent pelvic sonography. The girls were divided into 4 groups based on age and whether the GnRH stimulation test showed evidence of central puberty. Subanalyses were also conducted within each group based on peak luteinizing hormone (LH) level quartiles. RESULTS: Basal serum LH level was the most sensitive marker for screening CPP and EP. The cutoff values were 0.245 IU/L for CPP under 8 years old (P=0.049, area under the curve [AUC]=0.764, 88% sensitivity, 48% specificity) and 0.275 IU/L for EP between 8–9 years old (P=0.005, AUC=0.813, 79% sensitivity, 77% specificity). Peak LH level decreased as BMI z-score among subgroups increased when there was no difference in BA; however, higher BA eliminated this effect. CONCLUSION: Basal serum LH level is a useful screening parameter for diagnosing CPP and EP in girls. Peak LH levels were lower with increasing BMI z-score, although older BA eliminated this effect.

Morning basal luteinizing hormone, a good screening tool for diagnosing central precocious puberty

PURPOSE: The standard method used to diagnose central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test (GnRHST). However, this test is inconvenient for children because it is time-consuming and requires multiple samples. This study aimed to determine the reliability of morning unstimulated luteinizing hormone (mLH) level when screening for CPP, with an emphasis on the influence of diurnal variation. METHODS: This study included 160 girls with signs of early puberty (SMR 2) under 8 years of age. They were classified as CPP or non-CPP based on their standard GnRHST. The auxological, biochemical, and hormonal characteristics of subjects were retrospectively evaluated. The prognostic value of single morning unstimulated gonadotropin level was examined for use in CPP screening. RESULTS: Of 160 patients, 121 (75.6%) presented with CPP, and 39 (24.4%) were determined to be prepubertal. The mLH/mFSH (morning unstimulated follicular stimulating hormone) ratio showed significant differences between the 2 groups (P<0.001). The mLH was correlated with GnRHST variables (r=0.532, P<0.001). The mLH cutoff point when screening for CPP was 0.22 IU/L, which had sensitivity and specificity of 69.4% and 82.1%, respectively. In regression analysis, bone age (BA) (odds ratio [OR], 1.018; 95% confidence interval [CI], 0.967–1.071; P=0.506) and body mass index (BMI) (OR, 0.874; 95% CI, 0.583–1.310; P=0.515) were not significant predictors. The mLH≥0.22 IU/L group (OR, 9.596; 95% CI, 3.853–23.900; P<0.001) was highly suggestive of CPP. CONCLUSIONS: In this study, single morning unstimulated luteinizing hormone had clinical efficacy for CPP screening, but BA advanced over chronological age and BMI was not useful for CPP screening.

Poorly-Controlled Type 1 Diabetes Mellitus Impairs LH-LHCGR Signaling in the Ovaries and Decreases Female Fertility in Mice

PURPOSE: The aim of this study was to investigate how type I diabetes mellitus (T1D) affects the folliculogenesis and oocyte development, fertilization, and embryo development. MATERIALS AND METHODS: A comparative animal study was conducted using two different mouse models of T1D, a genetic AKITA model and a streptozotocin-induced diabetes model. Ovarian function was assessed by gross observation, immunoblot, immunohistochemistry, oocyte counting, and ELISA for serum hormones (insulin, anti-Mullerian hormone, estradiol, testosterone, and progesterone). Maturation and developmental competence of metaphase II oocytes from control and T1D animals was evaluated by immunofluorescent and immunohistochemical detection of biomarkers and in vitro fertilization. RESULTS: Animals from both T1D models showed increased blood glucose levels, while only streptozotocin (STZ)-injected mice showed reduced body weight. Folliculogenesis, oogenesis, and preimplantation embryogenesis were impaired in both T1D mouse models. Interestingly, exogenous streptozotocin injection to induce T1D led to marked decreases in ovary size, expression of luteinizing hormone/chorionic gonadotropin receptor in the ovaries, the number of corpora lutea per ovary, oocyte maturation, and serum progesterone levels. Both T1D models exhibited significantly reduced pre-implantation embryo quality compared with controls. There was no significant difference in embryo quality between STZ-injected and AKITA diabetic mice. CONCLUSION: These results suggest that T1D affects folliculogenesis, oogenesis, and embryo development in mice. However, the physiological mechanisms underlying the observed reproductive effects of diabetes need to be further investigated.

Long-term Results of Taking Anti-oxidant Nutritional Supplement in Intermediate Age-related Macular Degeneration

PURPOSE: We prospectively investigated clinical changes and long-term outcomes after administration of the drugs recommended by the Age-Related Eye Disease Study-2 to patients with intermediate age-related macular degeneration (AMD). METHODS: This prospective multicenter study enrolled 79 eyes of 55 patients taking lutein and zeaxanthin. The primary endpoint was contrast sensitivity; this was checked every 12 months for a total of 36 months after treatment commenced. The secondary endpoints were visual acuity, central macular thickness, and drusen volume; the latter two parameters were assessed using spectral domain optical coherence tomography. RESULTS: The mean patient age was 72.46 ± 7.16 years. Contrast sensitivity gradually improved at both three and six cycles per degree. The corrected visual acuity was 0.13 ± 0.14 logMAR and did not change significantly over the 36 months. Neither the central macular thickness nor drusen volume changed significantly. CONCLUSIONS: Contrast sensitivity markedly improved after treatment, improving vision and patient satisfaction. Visual acuity, central retinal thickness, and drusen volume did not deteriorate. Therefore, progression of AMD and visual function deterioration were halted.

Histological classification of canine ovarian cyst types with reference to medical history

Ovaries of 21 bitches presented with gynecopathies were surgically removed and histologically examined. Standard histological, as well as immunohistochemical, classification of 193 cystic structures resulted in the classification of 72 cysts of subsurface epithelial structures (SES), 61 follicular cysts (FCs), 38 cystic rete ovarii (CRO), 13 lutein cysts (LCs), and 9 non-classifiable cysts (NCCs). In addition to the histological classification, results were interpreted according to subject medical history, clinical examination outcome, and macroscopic observations during ovariohysterectomy. Dogs with ovarian cysts (OCs) and associated reproductive perturbations were mostly nulliparous, of large breed, and had an average of 9.5 ± 3 years. Prolonged or shortened inter-estrus intervals of past heats, however, seemed to be relatively low-risk factors for the development of OCs in dogs. Furthermore, we provide histological observations of a rarely seen canine LC including a degenerated oocyte in the central cavity.

Efficacy of luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist priming protocol in poor responders undergoing in vitro fertilization

OBJECTIVES: We investigated whether luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist (E/G-ant) priming protocol improves clinical outcomes in poor responders to controlled ovarian stimulation for in vitro fertilization (IVF)-embryo transfer, and identified underlying mechanisms. METHODS: This restrospective study consisted of 65 poor responders who underwent the E/G-ant priming protocol. Sixty-four other poor responders undergoing conventional protocols without pretreatment were included as the control group. Clinical outcomes were compared between 2 groups. RESULTS: The E/G-ant priming protocol group exhibited improvements over the control group in terms of the number of retrieved oocytes (3.58±2.24 vs. 1.70±1.45; P=0.000), mature oocytes (2.68±2.11 vs. 1.65±1.23; P=0.000), fertilized oocytes (2.25±1.74 vs. 1.32±1.26; P=0.001), good embryos (1.62±0.91 vs. 1.14±0.90, P=0.021). Day 3 follicle-stimulating hormone (FSH; 8.40±4.84 vs. 16.39±13.56; P=0.000) and pre-ovulation progesterone levels (0.67 vs. 1.28 ng/mL; P=0.016) were significantly higher in the control group than in the E/G-ant priming group. The overall rate of positive human chorionic gonadotropin tests was higher in the E/G-ant priming group than in the control group (32.3% vs.16.1%; P=0.039). Also, clinical pregnancy rate (26.2% vs. 12.5%; P=0.048) and the rate of live births (23.1% vs. 7.1%; P=0.023) were significantly higher in the E/G-ant priming group than in the control group. CONCLUSION: The E/G-ant priming protocol would lead to promising results in poor responders to IVF by suppressing endogenous FSH and by preventing premature luteinization.

Efficacy of Combined Aromatase Inhibitor and Luteinizing Hormone-Releasing Hormone Agonist in Premenopausal Metastatic Breast Cancer

PURPOSE: Endocrine therapy is the preferred treatment for hormone receptor (HR)-positive metastatic breast cancer (MBC). We investigated the efficacy of combined aromatase inhibitor (AI) and luteinizing hormone-releasing hormone (LHRH) agonist in premenopausal patients with HR-positive MBC. METHODS: We retrospectively analyzed the medical records of 21 HR-positive premenopausal MBC patients treated with combined AI and LHRH agonist therapy. RESULTS: The median follow-up period was 32.9 months. The overall response rate was 47.6%, with three complete responses (14.3%) and seven partial responses (33.3%). Nine patients (42.9%) achieved stable disease lasting more than 6 months; thus, the clinical benefit rate was 90.4%. The median time to progression was 45.4 months. No patients experienced grade 3 or 4 toxicity. CONCLUSION: Combined AI and LHRH agonist treatment safely and effectively induced remission or prolonged disease stabilization, suggesting that this could be a promising treatment option for HR-positive premenopausal patients with MBC.

Delayed puberty versus hypogonadism: a challenge for the pediatrician

Constitutional delay of growth and puberty (CDGP) is the most common cause of delayed puberty (DP), is mainly found in males, and is characterized by short stature and delayed skeletal maturation. A family history of the subject comprising the timing of puberty in the parents and physical examination may provide clues regarding the cause of DP. Delayed onset of puberty is rarely considered a disease in either sex. In fact, DP usually represents a common normal variant in pubertal timing, with favorable outcomes for final height and future reproductive capacity. In adolescents with CDGP, a linear growth delay occurs until immediately before the start of puberty, then the growth rate rapidly increases. Bone age is often delayed. CDGP is a diagnosis of exclusion; therefore, alternative causes of DP should be considered. Functional hypogonadotropic hypogonadism may be observed in patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions including celiac disease, inflammatory bowel diseases, kidney insufficiency, and anorexia nervosa. Permanent hypogonadotropic hypogonadism (pHH) showing low serum value of testosterone or estradiol and blunted follicle-stimulating hormones (FSH) and luteinizing hormones (LH) levels may be due to abnormalities in the central nervous system. Therefore, magnetic resonance imaging is necessary to exclude morphological abnormalities and neoplasia. Moreover, pHH may be isolated, as observed in Kallmann syndrome, or associated with other hormone deficiencies, as found in panhypopituitarism. Baseline or gonadotropin-releasing hormone pituitary stimulated gonadotropin level is not sufficient to easily differentiate CDGP from pHH. Low serum testosterone in male patients and low estradiol values in female patients, associated with high serum FSH and LH levels, suggest a diagnosis of hypergonadotropic hypogonadism. A genetic analysis can reveal a chromosomal abnormality (e.g., Turner syndrome or Klinefelter syndrome). In cases where the adolescent with CDGP is experiencing psychological difficulties, treatment should be recommended.

Hypogonadotrophic hypogonadism due to a mutation in the luteinizing hormone β-subunit gene

No abstract available.

The effect of overweight on the luteinizing hormone level after gonadorelin stimulation test in girls with idiopathic central precocious puberty

PURPOSE: We investigated the effect of overweight on luteinizing hormone (LH) levels after a gonadorelin stimulation test in Korean girls with idiopathic central precocious puberty (CPP). METHODS: Medical records of 234 girls diagnosed with idiopathic CPP were reviewed retrospectively. CPP was diagnosed when the peak LH levels after gonadorelin stimulation was >5.0 U/L. The enrolled girls had a peak LH level >5.0 U/L after a gonadorelin stimulation test. Selected girls were classified as normoweight (body mass index [BMI] below the 85th percentile with respect to age) and overweight (BMI greater than the 85th percentile with respect to age). RESULTS: The peak LH (8.95±2.85 U/L vs. 11.97±8.42 U/L, P < 0.01) and peak follicle-stimulating hormone (9.60±2.91 U/L vs. 11.17±7.77 U/L, P=0.04) after gonadorelin stimulation were lower in overweight girls with idiopathic CPP than in normoweight girls with idiopathic CPP. Being overweight was negatively associated with peak LH levels after gonadorelin stimulation test (odds ratio, 0.89; 95 % confidence interval, 0.81–0.98, P=0.02). CONCLUSIONS: In girls with idiopathic CPP, being overweight led to a lower LH peak after gonadorelin stimulation. Further research is needed to better understand the role of overweight on gonadotropin secretion in precocious puberty.

Thyroid function/antibodies in sudanese women with polycystic ovarian disease

OBJECTIVE: To evaluate thyroid function and hormonal profile in women with polycystic ovary syndrome (PCOS). METHODS: A case-control study was conducted at Saad Abualila Center, Khartoum, Sudan. The cases were women with confirmed PCOS based on Rotterdam criteria. The controls were infertile women with no evidence of PCOS. The socio-demographic characteristics and medical history were gathered using a questionnaire. Thyroid hormones (thyroid-stimulating hormone, free tri-iodothyronine, and free thyroxine), anti-thyroid peroxidase, and anti-thyroglobulin antibodies were measured. RESULTS: While there were no significant differences in the age and haemoglobin levels of the two studied groups (55 women in each arm), body mass index was significantly higher in women with PCOS. There were no significant differences in the levels of thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone, luteinizing hormone/follicle stimulating hormone, anti-thyroid peroxidase, anti-thyroglobulin antibodies, cholesterol, triglycerides and low-density lipoprotein cholesterol between the cases and the controls. The mean±standard deviation of free tri-iodothyronine (3.50±0.2 vs. 3.38±0.3 pg/mL, P=0.040) and median (interquartile) high-density lipoprotein cholesterol (37.0 [34.0 to 42.0] vs. 35.80 [29.0 to 41.0] mg/dL, P=0.015) were significantly higher in PCOS patients compared with the control group. In linear regression, PCOS (0.151 pg/mL, P=0.023) and anti-thyroid peroxidase levels (-0.078 pg/mL, P=0.031) were significantly associated with free tri-iodothyronine. CONCLUSION: Free tri-iodothyronine was a significantly higher among PCOS patients compared with the control group.

Comment on “Hypogonadotrophic hypogonadism due to a mutation in the luteinizing hormone β-subunit gene”

No abstract available.

Response to comment on “Hypogonadotrophic hypogonadism due to a mutation in the luteinizing hormone β-subunit gene”

No abstract available.

Restoration of Spermatogenesis Using a New Combined Herbal Formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an Luteinizing Hormone-Releasing Hormone Agonist-Induced Rat Model of Male Infertility

PURPOSE: We investigated the protective effect of a mixture of 2 herbal extracts, KH-465, which consisted of Epimedium koreanum Nakai and Angelica gigas Nakai, on spermatogenesis in a luteinizing hormone-releasing hormone (LHRH) agonist-induced rat model of male infertility. MATERIALS AND METHODS: Seventy-five 12-week-old male Sprague-Dawley rats were randomly divided into 5 groups, containing 15 rats each: a normal control group that received no treatment and 4 experimental groups (I, II, III, and IV) in which an LHRH agonist was administered for 4 weeks to induce spermatogenic failure. Group I received distilled water, and groups II, III, and IV received 200 mg/kg/day of KH-465, 400 mg/kg/day KH-465, and depo-testosterone for 4 weeks, respectively. Weight changes of the testis and epididymis, sperm count motility, and levels of testosterone (T), free T, follicle-stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were estimated. RESULTS: Body, testis, and epididymis weight showed no significant differences among the control and experimental groups. Treatment with KH-465 increased the sperm count and motility. Serum hormone levels of T, free T, and FSH were not significantly different in the experimental groups, while the LH level was higher than in the LHRH agonist-induced control group, but not to a significant extent. Levels of SOD were higher and 8-OHdG were lower in the groups that received KH-465 than in the LHRH agonist-induced control group. CONCLUSIONS: Our results suggest that KH-465 increased sperm production via reducing oxidative stress and had a positive effect in a male infertility model.

Association of serum carotenoid, retinol, and tocopherol concentrations with the progression of Parkinson's Disease

BACKGROUND/OBJECTIVES: A pivotal role of oxidative stress has been emphasized in the pathogenesis as well as in the disease progression of Parkinson's disease (PD). We aimed at investigating serum levels of antioxidant vitamins and elucidating whether they could be associated with the pathogenesis and progression of PD. MATERIALS/METHODS: Serum levels of retinol, α- and γ-tocopherols, α- and β-carotenes, lutein, lycopene, zeaxanthin and β-cryptoxanthin were measured and compared between 104 patients with idiopathic PD and 52 healthy controls matched for age and gender. In order to examine the relationship between antioxidant vitamins and the disease progression, multiple group comparisons were performed among the early PD (Hoehn and Yahr stage I and II, N = 47), advanced PD (stage III and IV, N = 57) and control groups. Separate correlation analyses were performed between the measured antioxidant vitamins and clinical variables, such as Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale (UPDRS) motor score. RESULTS: Compared to controls, PD patients had lower levels of α- and β-carotenes and lycopene. α-carotene, β-carotene and lycopene levels were significantly reduced in advanced PD patients relative to early PD patients and were negatively correlated with Hoehn and Yahr stage and UPDRS motor score in PD patients. No significant differences were found in serum levels of retinol, α- and γ-tocopherols, and other carotenoids between PD patients and controls. No significant correlations were found between these vitamin levels and clinical variables in PD patients. CONCLUSIONS: We found that serum levels of some carotenoids, α-carotene, β-carotene and lycopene, were lower in PD patients, and that these carotenoids inversely correlated with clinical variables representing disease progression. Our findings suggest that decreases in serum α-carotene, β-carotene and lycopene may be associated with the pathogenesis as well as progression of PD.

Adult granulosa cell tumors of the ovary: a retrospective study of 30 cases with respect to the expression of steroid synthesis enzymes / 부인종양

OBJECTIVE: Some, but not all, granulosa cell tumors are characterized by estrogen production. This study was designed to determine whether there are clinical or pathological variations in granulosa cell tumors in relation to the expression of sex steroid synthesis enzymes. METHODS: Clinical symptoms, serum hormonal values, and histology of 30 granulosa cell tumor patients who underwent surgery between 2002 and 2014 were retrospectively reviewed. RESULTS: Most patients presented with abnormal genital bleeding including abnormal menstrual cycles. Eight of 16 patients older than 50 years had endometrial hyperplasia and one had endometrial cancer. Serum 17β-estradiol (E2) levels tended to be higher in patients over 50 years of age (p=0.081). Serum follicle-stimulating hormone (FSH) levels were low in all patients irrespective of serum E2 levels. Magnetic resonance imaging revealed a thicker endometrium in older as compared to younger patients (p<0.05). Tumor cells in the majority of cases were positive for inhibin α and P450 aromatase, irrespective of age and serum E2 levels. P450 17α-hydroxylase (P450c17) expression varied among cases. P450c17 was strongly positive in luteinized tumor cells and weakly positive in theca cells and fibroblasts. High E2 levels were associated with P450c17-positive cells in the tumor (p<0.05). CONCLUSION: The expression of hormone-synthesizing enzymes divides granulosa cell tumors into 2 distinct types; tumors with P450c17-positive cells show elevated serum E2 and related clinical symptoms, while tumors without these cells show symptoms related to FSH suppression by inhibin.