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ELife Feb 2024Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used...
BACKGROUND
Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG.
METHODS
Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots.
RESULTS
Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression.
CONCLUSIONS
Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression.
FUNDING
This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).
Topics: Humans; Androstenedione; Bayes Theorem; Biomarkers; China; Cross-Sectional Studies; Glaucoma, Angle-Closure; Prospective Studies; Visual Fields
PubMed: 38358793
DOI: 10.7554/eLife.91407 -
Chemosphere Aug 2023Wastewater monitoring and epidemiology have seen renewed interest during the recent COVID-19 pandemic. As a result, there is an increasing need to normalize... (Review)
Review
Wastewater monitoring and epidemiology have seen renewed interest during the recent COVID-19 pandemic. As a result, there is an increasing need to normalize wastewater-derived viral loads in local populations. Chemical tracers, both exogenous and endogenous compounds, have proven to be more stable and reliable for normalization than biological indicators. However, differing instrumentation and extraction methods can make it difficult to compare results. This review examines current extraction and quantification methods for ten common population indicators: creatinine, coprostanol, nicotine, cotinine, sucralose, acesulfame, androstenedione 5-hydroindoleacetic acid (5-HIAA), caffeine, and 1,7-dimethyluric acid. Some wastewater parameters such as ammonia, total nitrogen, total phosphorus, and daily flowrate were also evaluated. The analytical methods included direct injection, dilute and shoot, liquid/liquid, and solid phase extraction (SPE). Creatine, acesulfame, nicotine, 5-HIAA and androstenedione have been analysed by direct injection into LC-MS; however, most authors prefer to include SPE steps to avoid matrix effects. Both LC-MS and GC-MS have been successfully used to quantify coprostanol in wastewater, and the other selected indicators have been quantified successfully with LC-MS. Acidification to stabilize the sample before freezing to maintain the integrity of samples has been reported to be beneficial. However, there are arguments both for and against working at acidic pHs. Wastewater parameters mentioned earlier are quick and easy to quantify, but the data does not always represent the human population effectively. A preference for population indicators originating solely from humans is apparent. This review summarises methods employed for chemical indicators in wastewater, provides a basis for choosing an appropriate extraction and analysis method, and highlights the utility of accurate chemical tracer data for wastewater-based epidemiology.
Topics: Humans; Wastewater; Nicotine; RNA, Viral; SARS-CoV-2; Hydroxyindoleacetic Acid; Androstenedione; Cholestanol; Pandemics; Water Pollutants, Chemical; COVID-19; Solid Phase Extraction; Indicators and Reagents
PubMed: 37201600
DOI: 10.1016/j.chemosphere.2023.138682 -
Journal of Ovarian Research 2014Weight gain and fat accumulation are predisposing factors of PCOS. Life-style modification, including increasing physical activity, is the first line approach in...
INTRODUCTION
Weight gain and fat accumulation are predisposing factors of PCOS. Life-style modification, including increasing physical activity, is the first line approach in managing PCOS. The objective of this study is to assess the effect of exercise intensity on weight changes, androstenedione and free testosterone level in female rats with estradiol valerate induced PCOS.
METHOD AND MATERIALS
40 female Wistar rats were selected (180 ± 20 g). They had every 2 to 3 consecutive estrous cycles during 12 to 14 days. The study was approved by ethical committee of Jahrom University of Medical Sciences. The first two groups were divided into control (n = 10) and polycystic (n = 30) that were induced PCOS by estradiol valerate injection after 60 days. The polycystic groups were divided into three groups of sham (n = 10), experiment group with low-intensity exercise (pco + l.exe) (n = 10) and experiment group with moderate intensity exercise (pco + m.exe) (n = 10). Exercises were performed during 6 sessions of 60 minutes per week for 8 weeks. (Moderate intensity: 28 m/min-70%-75%VO2Max. Low intensity (20 m/min-50%-55%VO2Max) running at 0 slope, 1 h/day, 6 days/week). ANOVA and LSD test were used for data analysis.
RESULTS
In the present study, no significant differences were found in the decrease of total weights of rats. And also androstenedione level changes in experiment groups were higher compared to control group but no significant differences were found, also free testosterone level was significantly higher than the observer group.
CONCLUSION
According to weight changes and sexual hormones (Free testosterone and androstenedione) exercise training especially with low intensity may improve symptoms of polycystic ovary syndrome.
Topics: Androstenedione; Animals; Estradiol; Exercise Therapy; Female; Polycystic Ovary Syndrome; Rats, Wistar; Running; Testosterone; Weight Loss
PubMed: 24708600
DOI: 10.1186/1757-2215-7-37 -
Clinical Endocrinology Sep 2022We examined if measurement of adrenal androgens adds to subtype diagnostics of primary aldosteronism (PA) under cosyntropin-stimulated adrenal venous sampling (AVS).
OBJECTIVE
We examined if measurement of adrenal androgens adds to subtype diagnostics of primary aldosteronism (PA) under cosyntropin-stimulated adrenal venous sampling (AVS).
DESIGN
A prospective pre-specified secondary endpoint analysis of 49 patients with confirmed PA, of whom 29 underwent unilateral adrenalectomy with long-term follow-up.
METHODS
Concentrations of androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were measured during AVS in addition to aldosterone and cortisol. Subjects with lateralisation index (LI) of ≥4 were treated with unilateral adrenalectomy, and the immunohistochemical subtype was determined with CYP11B2 and CYP11B1 stains. The performance of adrenal androgens was evaluated by receiver operating characteristics (ROC) curve analyses in adrenalectomy and medical therapy groups.
RESULTS
During AVS, the correlations between cortisol and androstenedione, DHEA and DHEAS for LI and selectivity index (SI) were highly significant. The right and left side SIs for androstenedione and DHEA were higher (p < .001) than for cortisol. In ROC analysis, the optimal LI cut-off values for androstenedione, DHEA and DHEAS were 4.2, 4.5 and 4.6, respectively. The performance of these LIs for adrenal androgens did not differ from that of cortisol.
CONCLUSIONS
Under cosyntropin-stimulated AVS, the measurement of androstenedione and DHEA did not improve the cannulation selectivity. The performance of cortisol and adrenal androgens are confirmatory but not superior to cortisol-based results in lateralisation diagnostics of PA.
Topics: Adrenal Glands; Aldosterone; Androgens; Androstenedione; Cosyntropin; Dehydroepiandrosterone; Humans; Hydrocortisone; Hyperaldosteronism; Prospective Studies; Retrospective Studies
PubMed: 35167715
DOI: 10.1111/cen.14691 -
The Journal of Clinical Endocrinology... Jan 2022
Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Androstenedione; Humans
PubMed: 34331764
DOI: 10.1210/clinem/dgab555 -
British Journal of Clinical Pharmacology Mar 2021The aim of this study was to characterize the pharmacokinetic/pharmacodynamic relationships of cortisol and the adrenal biomarkers 17-hydroxyprogesterone and...
AIMS
The aim of this study was to characterize the pharmacokinetic/pharmacodynamic relationships of cortisol and the adrenal biomarkers 17-hydroxyprogesterone and androstenedione in children with congenital adrenal hyperplasia (CAH).
METHODS
A nonlinear mixed-effect modelling approach was used to analyse cortisol, 17-hydroxyprogesterone and androstenedione concentrations obtained over 6 hours from children with CAH (n = 50). A circadian rhythm was evident and the model leveraged literature information on circadian rhythm in untreated children with CAH. Indirect response models were applied in which cortisol inhibited the production rate of all three compounds using an I model.
RESULTS
Cortisol was characterized by a one-compartment model with apparent clearance and volume of distribution estimated at 22.9 L/h/70 kg and 41.1 L/70 kg, respectively. The IC values of cortisol concentrations for cortisol, 17-hydroxyprogesterone and androstenedione were estimated to be 1.36, 0.45 and 0.75 μg/dL, respectively. The inhibitory effect was found to be more potent on 17OHP than D4A, and the IC values were higher in salt-wasting subjects than simple virilizers. Production rates of cortisol, 17-hydroxyprogesterone and androstenedione were higher in simple-virilizer subjects. Half-lives of cortisol, 17-hydroxyprogesterone and androstenedione were 60, 47 and 77 minutes, respectively.
CONCLUSION
Rapidly changing biomarker responses to cortisol concentrations highlight that single measurements provide volatile information about a child's disease control. Our model closely captured observed cortisol, 17-hydroxyprogesterone and androstenedione concentrations. It can be used to predict concentrations over 24 hours and allows many novel exposure metrics to be calculated, e.g., AUC, AUC-above-threshold, time-within-range, etc. Our long-range goal is to uncover dose-exposure-outcome relationships that clinicians can use in adjusting hydrocortisone dose and timing.
Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Androstenedione; Biomarkers; Child; Humans; Hydrocortisone
PubMed: 32652643
DOI: 10.1111/bcp.14470 -
National Toxicology Program Technical... Sep 2010Androstenedione is an androgen steroid that is normally synthesized within men and women and may be metabolized to a more potent androgen or estrogen hormone. It was... (Review)
Review
UNLABELLED
Androstenedione is an androgen steroid that is normally synthesized within men and women and may be metabolized to a more potent androgen or estrogen hormone. It was nominated to the National Toxicology Program for study due to concern for adverse health effects associated with its chronic use as a dietary supplement by athletes (prior to the banning of its over the counter sales). In order to evaluate its subchronic and chronic toxicity, male and female F344/N rats and B6C3F1 mice were administered androstenedione (98% pure) by gavage for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, rat bone marrow cells, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: groups of five male and five female rats were administered 0, 1, 5, 10, 20, or 50 mg androstenedione/kg body weight in a 0.5% aqueous methylcellulose solution by gavage, 5 days per week for 12 days. All rats survived to the end of the study, and the mean body weights of dosed groups were similar to those of the vehicle control groups. The development of cytoplasmic vacuoles within centrilobular hepatocytes in male rats was the only treatment-related effect observed. 2-WEEK STUDY IN MICE: groups of five male and five female mice were administered 0, 1, 5, 10, 20, or 50 mg androstenedione/kg body weight in a 0.5% aqueous methylcellulose solution by gavage, 5 days per week for 12 days. One vehicle control female, one 20 mg/kg female, and one 50 mg/kg female died early due to gavage accidents. There were no significant chemical-related histopathological or mean body weight changes. 3-MONTH STUDY IN RATS: groups of 10 male and 10 female core study rats were administered 0, 1, 5, 10, 20, or 50 mg androstenedione/kg body weight in a 0.5% aqueous methylcellulose solution by gavage, 5 days per week for 14 weeks; additional groups of 10 male and 10 female clinical pathology study rats received the same doses for 23 days. All rats survived to the end of the study. The mean body weights of the 20 mg/kg female group was significantly greater than those of the vehicle control group and there was significant increased weight gain in the 1, 20, and 50 mg/kg female groups. Female thymus weights were significantly increased in the 20 and 50 mg/kg groups, which may be related to the increase in mean body weight. The numbers of sperm per mg cauda epididymis in the 10, 20, and 50 mg/kg male groups and the total number of sperm per cauda epididymis in 50 mg/kg males were significantly less than those of the vehicle controls. No treatment-related histological lesions were observed in males or females. 3-MONTH STUDY IN MICE: groups of 10 male and 10 female mice were administered 0, 1, 5, 10, 20, or 50 mg androstenedione/kg body weight in a 0.5% aqueous methylcellulose solution by gavage, 5 days per week for 14 weeks. Except for one 10 mg/kg female that died early due to a dosing accident, all mice survived to the end of the study. The mean body weights of dosed groups were similar to those of the vehicle control groups. The number of spermatids per mg testis and the total number of spermatids per testis in 20 mg/kg males were significantly greater than those of the vehicle controls. Sperm motility in 50 mg/kg males was significantly lower than that in the vehicle controls. The incidences of x-zone atrophy of the adrenal cortex, an androgen-sensitive endpoint, were significantly increased in females administered 5 mg/kg or greater. There were also significant decreases in the incidences of x-zone cytoplasmic vacuolization in 20 and 50 mg/kg females. The incidences of bone marrow hyperplasia were significantly increased in 5 and 50 mg/kg males. 2-YEAR STUDY IN RATS: groups of 50 male and 50 female rats were administered 0, 10, 20, or 50 mg androstenedione/kg body weight in a 0.5% aqueous methylcellulose solution by gavage, 5 days per week for at least 104 weeks. Survival of 10 mg/kg males was significantly greater than that of the vehicle controls. The mean body weights of 20 and 50 mg/kg females were greater than those of the vehicle controls after weeks 17 and 9, respectively. The incidences of mononuclear cell leukemia were significantly increased in 20 and 50 mg/kg females and significantly decreased in 20 and 50 mg/kg males. Incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in 20 mg/kg males. The incidence of testicular interstitial cell adenoma (including bilateral) was significantly decreased in 50 mg/kg males. In females, the incidences of mammary gland fibroadenoma were significantly decreased in the 20 and 50 mg/kg groups, the incidences of mammary gland hyperplasia were significantly decreased in all dosed groups, and the incidences of mammary gland cyst were significantly decreased in the 10 and 50 mg/kg groups. In the liver of males, the incidences of basophilic focus in all dosed groups, the incidence of clear cell focus in the 20 mg/kg group, and the incidence of eosinophilic focus in the 50 mg/kg group were significantly increased. The incidences of pancreatic islet hyperplasia and atrophy of the exocrine pancreas were significantly increased in 50 mg/kg females. 2-YEAR STUDY IN MICE: groups of 50 male and 50 female mice were administered 0, 2 (females only), 10, 20 (males only), or 50 mg androstenedione/kg body weight in a 0.5% aqueous methylcellulose solution by gavage, 5 days per week for at least 104 weeks. Survival of dosed groups was similar to that of the vehicle control groups. Mean body weights of 10 and 50 mg/kg females were generally less than those of the vehicle controls after weeks 81 and 17, respectively. The incidences of hepatocellular adenoma in males and females were significantly increased in the 50 mg/kg groups. In females, the incidences of hepatocellular carcinoma were significantly increased in all dosed groups. Incidences of hepatocellular adenoma or carcinoma (combined) in males and females were significantly increased in the 50 mg/kg groups. Incidences of hepatoblastoma were marginally increased in dosed males. Incidences of multiple hepatocellular adenomas and carcinomas were significantly increased in 10 and 50 mg/kg males, and there was an increased incidence of multiple hepatocellular adenomas in 50 mg/kg females. The incidence of eosinophilic focus was significantly increased in 50 mg/kg males, and the incidences of mixed cell focus and cytoplasmic vacuolization were significantly increased in 50 mg/kg females. There was a marginally increased incidence of pancreatic islet adenoma in 50 mg/kg males and in 10 and 50 mg/kg females, with an earlier day of first incidence in males. The incidences of clitoral gland hyperplasia and clitoral gland duct dilatation were significantly increased in 10 and 50 mg/kg females. The incidence of glomerular metaplasia of the kidney was significantly increased in 50 mg/kg females, and the incidences of cytoplasmic alteration of the submandibular salivary gland were significantly increased in all dosed female groups. The increased incidences of cytoplasmic alteration of the submandibular salivary gland and glomerular metaplasia of the kidney in female mice indicated a masculinizing effect from androstenedione treatment. In 50 mg/kg females, the incidence of malignant lymphoma was significantly decreased.
GENETIC TOXICOLOGY
androstenedione was not mutagenic in either of two independent bacterial mutation assays conducted with and without exogenous metabolic activation. No significant increases in the frequencies of micronucleated polychromatic erythrocytes, indicators of chromosomal damage, were observed in bone marrow of male rats administered androstenedione by gavage once daily for 3 consecutive days. Results of a peripheral blood erythrocyte micronucleus test in mice, in which androstenedione was administered by gavage for 3 months, were negative in males but judged to be equivocal in females due to a small increase (twofold over background) in micronucleated normochromatic erythrocytes observed at the highest dose administered (50 mg/kg).
CONCLUSIONS
under the conditions of these 2-year gavage studies, there was equivocal evidence of carcinogenic activity of androstenedione in male F344/N rats based on increased incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined). There was equivocal evidence of carcinogenic activity of androstenedione in female F344/N rats based on increased incidences of mononuclear cell leukemia. There was clear evidence of carcinogenic activity of androstenedione in male B6C3F1 mice based on increased incidences of multiple hepatocellular adenoma and hepatocellular carcinoma and increased incidence of hepatoblastoma. There was clear evidence of carcinogenic activity of androstenedione in female B6C3F1 mice based on increased incidences of hepatocellular adenoma and hepatocellular carcinoma. Increased incidences of pancreatic islet adenoma in male and female mice were also considered chemical related. Androstenedione administration caused increased incidences in nonneoplastic lesions of the liver in male and female rats and mice; pancreatic islets and exocrine pancreas of female rats; and clitoral gland, kidney, and submandibular salivary gland of female mice. Decreases in the incidences of testicular interstitial cell adenoma in male rats, mammary gland fibroadenoma, cysts, and hyperplasia in female rats, and malignant lymphoma in female mice were considered related to androstenedione administration. Synonyms: Andro; androst-4-ene-3,17-dione; 4-androstene-3,17-dione; delta-4-androstene-3,17-dione; delta-4-androstenedione; 3,17-dioxoandrost-4-ene; 17-ketotestosterone; SKF 2170 Trade names: Androtex, Fecundin.
Topics: Androstenedione; Animal Feed; Animals; Biomarkers; Body Weight; Carcinogenicity Tests; Chemical and Drug Induced Liver Injury; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Estrous Cycle; Female; Genitalia; Intubation, Gastrointestinal; Male; Mice; Mice, Inbred Strains; Micronucleus Tests; Mutagens; Organ Size; Rats; Rats, Inbred F344
PubMed: 21037592
DOI: No ID Found -
Hormones (Athens, Greece) Dec 2021The aim of the present literature review is to describe the influence of sex hormones on the human voice in physiological conditions. As a secondary sexual organ, the... (Review)
Review
The aim of the present literature review is to describe the influence of sex hormones on the human voice in physiological conditions. As a secondary sexual organ, the larynx is affected by sex hormones and may change considerably over the lifespan. In the current review, sex hormone-related voice modifications occurring during childhood, puberty, the menstrual cycle, pregnancy and senescence are described. The roles of sex hormones (including gonadotropins, testosterone, estrogen, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone-sulfate) underlying physiological voice changes are discussed, the main differences between males and females are explained and clinical implications are taken into account.
Topics: Androgens; Androstenedione; Dehydroepiandrosterone; Estrogens; Female; Gonadal Steroid Hormones; Gonadotropins; Humans; Male; Pregnancy; Testosterone; Voice
PubMed: 34046877
DOI: 10.1007/s42000-021-00298-y -
Psychoneuroendocrinology Aug 2021Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or...
BACKGROUND
Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core emotional symptoms such as sadness and anhedonia. We examined whether androgen levels 1) differ between men with and without MDD cross-sectionally, 2) are associated with an elevated risk for onset of MDD prospectively, and 3) associate with all individual MDD symptoms, or only with hypogonadism overlapping symptoms.
METHODS
In 823 men (mean age 43.5 years), baseline plasma levels of total testosterone, 5α-dihydrotestosterone (5α-DHT), and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulphate (DHEAS) and sex hormone binding globulin with radioimmunoassay, whereas free testosterone was calculated. MDD status was assessed at baseline and after two years using structured interviews and individual MDD symptoms were self-rated at baseline, and after one and two years.
RESULTS
None of the androgen levels were associated with current or onset (incidence or recurrence) of MDD. Free testosterone was only inversely associated with interest in sex. Also, androstenedione and DHEAS were positively associated with some individual MDD symptoms, and 5α-DHT levels showed non-linear associations (both with low and high levels) with MDD symptom severity and several individual MDD symptoms.
CONCLUSIONS
These results support the idea that circulating androgens synthesised by the testes are of limited clinical relevance to MDD in adult men, but levels of androstenedione, DHEAS and 5α-DHT may be associated with some individual MDD symptoms.
Topics: Adult; Androgens; Androstenedione; Dehydroepiandrosterone Sulfate; Depression; Depressive Disorder, Major; Dihydrotestosterone; Humans; Male; Sex Hormone-Binding Globulin; Testosterone
PubMed: 34049017
DOI: 10.1016/j.psyneuen.2021.105278 -
Journal of Animal Science Aug 2021Ovarian paracrine mediation by components of the wingless-type mouse mammary tumor virus integration site ligands (WNT1 to 11) and their receptors, frizzled family...
Ovarian paracrine mediation by components of the wingless-type mouse mammary tumor virus integration site ligands (WNT1 to 11) and their receptors, frizzled family members (FZD1 to 10), has been proposed. Secreted truncated forms of FZD proteins (e.g., secreted frizzled-related protein 4 [SFRP4]) block the action of WNT ligands. Dickkopf-1 (DKK1) is another WNT antagonist, and R-spondin-1 (RSPO1) is one of a group of four secreted proteins that enhance WNT/β-catenin signaling. Our hypothesis was that granulosa cells signal theca cells (TCs) via SFRP4, DKK1, RSPO1, and WNT secretion to regulate TC differentiation and proliferation. Therefore, in vitro experiments were conducted to study the effects of WNT family member 3A (WNT3A), WNT5A, RSPO1, DKK1, insulin-like growth factor 1 (IGF1), bone morphogenetic protein 7 (BMP7), Indian hedgehog (IHH), and fibroblast growth factor 9 (FGF9) on bovine TC proliferation and steroidogenesis. TCs of large (8 to 20 mm) and small (3 to 6 mm) follicles were collected from bovine ovaries; TC monolayers were established in vitro and treated with various doses of recombinant human WNT3A, WNT5A, RSPO1, DKK1, IGF1, FGF9, BMP7, IHH, and/or ovine luteinizing hormone (LH) in serum-free medium for 48 h. In experiment 1, using LH-treated TC, IGF1, IHH, and WNT3A increased (P < 0.05) cell numbers and androstenedione production, whereas WNT3A and BMP7 inhibited (P < 0.05) progesterone production. In experiment 2, FGF9 blocked (P < 0.05) the WNT3A-induced increase in androstenedione production in LH plus IGF1-treated TC. In experiment 3, RSPO1 further increased (P < 0.05) LH plus IGF1-induced progesterone and androstenedione production. In experiment 4, SFRP4 and DKK1 alone had no significant effect on TC proliferation or progesterone production of large-follicle TC but both blocked the inhibitory effect of WNT5A on androstenedione production. In contrast, DKK1 alone inhibited (P < 0.05) small-follicle TC androstenedione production whereas SFRP4 was without effect. We conclude that the ovarian TC WNT system is functional in cattle, with WNT3A increasing proliferation and androstenedione production of TC.
Topics: Androstenedione; Animals; Cattle; Cells, Cultured; Female; Granulosa Cells; Hedgehog Proteins; Humans; Mammary Tumor Virus, Mouse; Mice; Ovarian Follicle; Progesterone; Sheep; Theca Cells
PubMed: 34166505
DOI: 10.1093/jas/skab197