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International Journal of Molecular... Nov 2021A sufficient vascular network within the feto-maternal interface is necessary for placental function. Several pregnancy abnormalities have been associated with abnormal...
A sufficient vascular network within the feto-maternal interface is necessary for placental function. Several pregnancy abnormalities have been associated with abnormal vascular formations in the placenta. We hypothesized that growth and expansion of the placental vascular network in the equine () placenta is regulated by estrogens (estrogen family hormones), a hormone with a high circulating concentration during equine gestation. Administration of letrozole, a potent and specific inhibitor of aromatase, during the first trimester (D30 to D118), decreased circulatory estrone sulfate concentrations, increased circulatory testosterone and androstenedione concentrations, and tended to reduce the weight of the fetus ( < 0.1). Moreover, the gene expression of was increased, and the expression of androgen receptor was decreased in the D120 chorioallantois (CA) of letrozole-treated mares in comparison to that of the control mares. We also found that at D120, the number of vessels tended to decrease in the CAs with letrozole treatment ( = 0.07). In addition, expression of a subset of angiogenic genes, such as , , and , were altered in the CAs of letrozole-treated mares. We further demonstrated that 17β-estradiol increases the expression of and and increases the angiogenic activity of equine endothelial cells in vitro. Our results from the estrogen-suppressed group demonstrated an impaired placental vascular network, suggesting an estrogen-dependent vasculogenesis in the equine CA during the first trimester.
Topics: Androstenedione; Angiopoietin-1; Animals; Aromatase; Estrogens; Female; Gene Expression Regulation, Developmental; Horses; Letrozole; Maternal-Fetal Relations; Neovascularization, Physiologic; Placenta; Pregnancy; Pregnancy Trimester, First; Receptors, Androgen; Steroid 17-alpha-Hydroxylase; Testosterone; Vascular Endothelial Growth Factor A
PubMed: 34829994
DOI: 10.3390/ijms222212116 -
Clinical Endocrinology Nov 2021To document associations between anti-Müllerian hormone (AMH) and circulating androgens in nonhealthcare-seeking premenopausal women.
OBJECTIVE
To document associations between anti-Müllerian hormone (AMH) and circulating androgens in nonhealthcare-seeking premenopausal women.
DESIGN
Community-based, cross-sectional study.
SETTING
Eastern states of Australia.
PARTICIPANTS
Women aged 18-39 years not using systemic hormones, not pregnant or breastfeeding within 3 months, and not postmenopausal.
MEASUREMENTS
AMH, measured by the Beckman Access 2, 2 site immunometric assay from fresh samples, and testosterone, androstenedione, dehydroepiandrosterone (DHEA) and 11-oxygenated C19 steroids, measured by liquid chromatography-tandem mass spectrometry.
RESULTS
Data were available for 794 women, median age of 33 years (range: 18-39). 76.1% were of European ancestry and 48.2% were parous. Serum AMH was positively associated with testosterone (rho = .29, p < .001) androstenedione (rho = .39, p < .001) and DHEA (rho = .10, p = .005) but not 11-ketoandrostenedione or 11-ketotestosterone. When adjusted for age, body mass index and smoking, using quantile regression, independent positive associations remained between AMH and testosterone (β coefficient: 20.90, 95% confidence interval [CI]: 13.79-28.03; p < .001) and androstenedione (β coefficient: 5.90, 95% CI: 3.76-8.03; p < .001). The serum concentration of testosterone was greater at the top AMH quintile than other quintiles (0.56 nmol/L [range: 0.21-1.90] vs. 0.36 nmol/L [range: 0.13-0.87]; p = .001) in women with self-reported polycystic ovary syndrome.
CONCLUSIONS
The positive associations between serum testosterone and androstenedione and AMH in premenopausal women is consistent with androgens directly or indirectly influencing AMH production during follicular development. As the highest AMH concentrations are most likely to be seen in women with multifollicular ovaries, it would be expected that women with multifollicular ovaries would have higher serum testosterone. Therefore, whether hyperandrogenemia and multifollicular ovaries should be considered independent characteristics of polycystic ovary syndrome warrants review.
Topics: Adolescent; Adult; Androgens; Androstenedione; Anti-Mullerian Hormone; Cross-Sectional Studies; Female; Humans; Pregnancy; Testosterone; Young Adult
PubMed: 34524701
DOI: 10.1111/cen.14592 -
Methods in Molecular Biology (Clifton,... 2023Phytosterols, coming as a by-product of vegetable oils or wood pulp, contain the cyclopentanoperhydrophenanthrene nucleus and can be bioconverted into steroid...
Phytosterols, coming as a by-product of vegetable oils or wood pulp, contain the cyclopentanoperhydrophenanthrene nucleus and can be bioconverted into steroid intermediates by removing the C17 side chain. This chapter shows the scale-up, from flask to bioreactor, of phytosterols bioconversion into 4-androstene-3,17-dione (androstenedione; AD) using Mycolicibacterium neoaurum B-3805. Due to the fact that phytosterols and AD are nearly insoluble in water, two-phase systems and the use of chemically modified cyclodextrins have been described as methods to solve it. Here, we use a water-oil two-phase system that allows the bioconversion of up to 20 g/L of phytosterols into AD in 5 L and 20 L bioreactors.
Topics: Androstenedione; Androstenes; Bioreactors; Phytosterols; Water
PubMed: 37642848
DOI: 10.1007/978-1-0716-3385-4_14 -
Journal of Personalized Medicine Feb 2023The role of estrogens and progesterone in the development and progression of endometrial cancer is well-established, but there are very little data about the role of... (Review)
Review
The role of estrogens and progesterone in the development and progression of endometrial cancer is well-established, but there are very little data about the role of androgens. There are five different androgens produced in women: dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT). The most potent hormones are T and DHT, the latter being mainly produced from T in peripheral tissues, including endometrium. Although they are considered to exert antiproliferative effects in many settings and the expression of their receptors is more often associated with a good prognosis in EC, it is still unknown in which specific settings androgens have carcinogenic or protective effects in EC.
PubMed: 36836575
DOI: 10.3390/jpm13020341 -
Molecules (Basel, Switzerland) May 2022Androstenedione (AD) is a key intermediate in the body's steroid metabolism, used as a precursor for several steroid substances, such as testosterone, estradiol, ethinyl... (Review)
Review
Androstenedione (AD) is a key intermediate in the body's steroid metabolism, used as a precursor for several steroid substances, such as testosterone, estradiol, ethinyl estradiol, testolactone, progesterone, cortisone, cortisol, prednisone, and prednisolone. The world market for AD and ADD (androstadienedione) exceeds 1000 tons per year, which stimulates the pharmaceutical industry's search for newer and cheaper raw materials to produce steroidal compounds. In light of this interest, we aimed to investigate the progress of AD biosynthesis from phytosterols by prospecting scientific articles (Scopus, Web of Science, and Google Scholar databases) and patents (USPTO database). A wide variety of articles and patents involving AD and phytosterol were found in the last few decades, resulting in 108 relevant articles (from January 2000 to December 2021) and 23 patents of interest (from January 1976 to December 2021). The separation of these documents into macro, meso, and micro categories revealed that most studies (articles) are performed in China (54.8%) and in universities (76%), while patents are mostly granted to United States companies. It also highlights the fact that AD production studies are focused on "process improvement" techniques and on possible modifications of the "microorganism" involved in biosynthesis (64 and 62 documents, respectively). The most-reported "process improvement" technique is "chemical addition" (40%), which means that the addition of solvents, surfactants, cofactors, inducers, ionic liquids, etc., can significantly increase AD production. Microbial genetic modifications stand out in the "microorganism" category because this strategy improves AD yield considerably. These documents also revealed the main aspects of AD and ADD biosynthesis: sp. (basonym: sp.) (40%) and (known previously as ) (32%) are the most recurrent species studied. Microbial incubation temperatures can vary from 29 °C to 37 °C; incubation can last from 72 h to 14 days; the mixture is agitated at 140 to 220 rpm; vegetable oils, mainly soybean, can be used as the source of a mixture of phytosterols. In general, the results obtained in the present technological prospecting study are fundamental to mapping the possibilities of AD biosynthesis process optimization, as well as to identifying emerging technologies and methodologies in this scenario.
Topics: Androgens; Androstenedione; Biotransformation; Mycobacteriaceae; Phytosterols; Steroids
PubMed: 35630641
DOI: 10.3390/molecules27103164 -
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 -
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 -
Journal of Clinical Medicine Oct 2021Success of adrenal vein sampling (AVS) is verified by the selectivity index (SI), i.e., by a step-up of cortisol levels between the adrenal vein and the infrarenal...
Success of adrenal vein sampling (AVS) is verified by the selectivity index (SI), i.e., by a step-up of cortisol levels between the adrenal vein and the infrarenal inferior vena cava samples, beyond a given cut-off. We tested the hypothesis that androstenedione, metanephrine, and normetanephrine, which have higher gradients than cortisol, could increase the rate of AVS studies judged to be bilaterally successful and usable for the clinical decision making. We prospectively compared within-patient, head-to-head, the selectivity index of androstenedione (SI), metanephrine (SI), and normetanephrine (SI), and cortisol (SI) in consecutive hypertensive patients with primary aldosteronism submitted to AVS. Main outcome measures were rate of bilateral success, SI values, and identification of unilateral PA. We recruited 136 patients (55 + 10 years, 35% women). Compared to the SI, the SI values were 3.5-fold higher bilaterally, and the SI values were 7-fold and 4.4-fold higher on the right and the left side, respectively. With the SI and the SI the rate of bilaterally successful AVS increased by 14% and 15%, respectively without impairing the identification of unilateral PA. We concluded that androstenedione and metanephrine outperformed cortisol for ascertaining AVS success, thus increasing the AVS studies useable for the clinical decision making.
PubMed: 34682878
DOI: 10.3390/jcm10204755 -
The New England Journal of Medicine Jun 2024Adrenal insufficiency in patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is treated with glucocorticoid replacement therapy. Control...
BACKGROUND
Adrenal insufficiency in patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is treated with glucocorticoid replacement therapy. Control of adrenal-derived androgen excess usually requires supraphysiologic glucocorticoid dosing, which predisposes patients to glucocorticoid-related complications. Crinecerfont, an oral corticotropin-releasing factor type 1 receptor antagonist, lowered androstenedione levels in phase 2 trials involving patients with CAH.
METHODS
In this phase 3 trial, we randomly assigned adults with CAH in a 2:1 ratio to receive crinecerfont or placebo for 24 weeks. Glucocorticoid treatment was maintained at a stable level for 4 weeks to evaluate androstenedione values, followed by glucocorticoid dose reduction and optimization over 20 weeks to achieve the lowest glucocorticoid dose that maintained androstenedione control (≤120% of the baseline value or within the reference range). The primary efficacy end point was the percent change in the daily glucocorticoid dose from baseline to week 24 with maintenance of androstenedione control.
RESULTS
All 182 patients who underwent randomization (122 to the crinecerfont group and 60 to the placebo group) were included in the 24-week analysis, with imputation of missing values; 176 patients (97%) remained in the trial at week 24. The mean glucocorticoid dose at baseline was 17.6 mg per square meter of body-surface area per day of hydrocortisone equivalents; the mean androstenedione level was elevated at 620 ng per deciliter. At week 24, the change in the glucocorticoid dose (with androstenedione control) was -27.3% in the crinecerfont group and -10.3% in the placebo group (least-squares mean difference, -17.0 percentage points; P<0.001). A physiologic glucocorticoid dose (with androstenedione control) was reported in 63% of the patients in the crinecerfont group and in 18% in the placebo group (P<0.001). At week 4, androstenedione levels decreased with crinecerfont (-299 ng per deciliter) but increased with placebo (45.5 ng per deciliter) (least-squares mean difference, -345 ng per deciliter; P<0.001). Fatigue and headache were the most common adverse events in the two trial groups.
CONCLUSIONS
Among patients with CAH, the use of crinecerfont resulted in a greater decrease from baseline in the mean daily glucocorticoid dose, including a reduction to the physiologic range, than placebo following evaluation of adrenal androgen levels. (Funded by Neurocrine Biosciences; CAHtalyst ClinicalTrials.gov number, NCT04490915.).
PubMed: 38828955
DOI: 10.1056/NEJMoa2404656 -
Journal of the Endocrine Society Jul 2023Ovarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1...
CONTEXT
Ovarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1 11β-hydroxysteroid dehydrogenase, which modulate peripheral androgen and cortisol production.
OBJECTIVES
To compare serum adrenal steroids, including 11-oxygenated androgens (11-oxyandrogens), cortisol, and cortisone between normal-weight women with PCOS and body mass index- and age-matched ovulatory women with normal-androgenic profiles (controls), and assess whether adrenal steroids associate with abdominal adipose deposition.
DESIGN
Prospective, cross-sectional, cohort study.
SETTING
Academic medical center.
PATIENTS
Twenty normal-weight women with PCOS and 20 body mass index-/age-matched controls.
INTERVENTIONS
Blood sampling, IV glucose tolerance testing, and total-body dual-energy x-ray absorptiometry.
MAIN OUTCOME MEASURES
Clinical characteristics, hormonal concentrations, and body fat distribution.
RESULTS
Women with PCOS had higher serum total/free testosterone (T) and androstenedione (A4) levels and a greater android/gynoid fat mass than controls (androgens < .001; android/gynoid fat mass ratio, = .026). Serum total/free T and A4 levels correlated positively with android/gynoid fat mass ratio in all women combined ( < .025, all values). Serum 11ß-hydroxyA4, 11-ketoA4, 11ß-hydroxyT, 11-ketoT, cortisol, and cortisone levels were comparable between female types and unrelated to body fat distribution. Serum 11-oxyandrogens correlated negatively with % total body fat, but lost significance adjusting for cortisol. Serum cortisol levels, however, correlated inversely with android fat mass ( = .021), with a trend toward reduced serum cortisol to cortisone ratio in women with PCOS vs controls ( = .075), suggesting diminished 11β-hydroxysteroid dehydrogenase activity.
CONCLUSION
Reduced cortisol may protect against preferential abdominal fat mass in normal-weight PCOS women with normal serum 11-oxyandrogens.
PubMed: 37404244
DOI: 10.1210/jendso/bvad079