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The Prostate Nov 2017The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of...
BACKGROUND
The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume.
METHODS
Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI).
RESULTS
Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates.
CONCLUSIONS
STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase.
Topics: Aged; Androstenediol; Body Mass Index; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Estradiol; Estrone; Gas Chromatography-Mass Spectrometry; Gonadal Steroid Hormones; Humans; Male; Middle Aged; Prospective Studies; Prostate; Prostatic Hyperplasia; Testosterone; Urinary Bladder Neoplasms
PubMed: 28905453
DOI: 10.1002/pros.23429 -
Clinical Mass Spectrometry (Del Mar,... Jan 2019The recently identified alternate, or backdoor, pathway of DHT synthesis provides important novel information on androgen biosynthesis beyond the classical pathway. We...
Simultaneous measurement of 18 steroids in human and mouse serum by liquid chromatography-mass spectrometry without derivatization to profile the classical and alternate pathways of androgen synthesis and metabolism.
BACKGROUND
The recently identified alternate, or backdoor, pathway of DHT synthesis provides important novel information on androgen biosynthesis beyond the classical pathway. We report a rapid and versatile liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to simultaneously and accurately quantify key steroids in human or mouse serum involved in either the classical or backdoor androgen synthesis pathways.
METHODS
Serum (200 µL) fortified with isotopically labelled internal standards underwent liquid-liquid extraction (LLE) with MTBE and extracts were analysed on a LC-MS/MS. The targeted steroids for quantification were testosterone (T), dihydrotestosterone (DHT), 5α-androstane-3α,17β-diol (3α diol), 5α-androstane-3β,17β-diol (3β diol), dehydroepiandrosterone (DHEA), androstenedione (A4), androsterone (AD), estradiol (E2), estrone (E1), progesterone (P4), pregnenolone (P5), androstenediol (Adiol), 17-hydroxyprogesterone (17-OHP4) and 17-hydroxypregnenolone (17-OHP5), corticosterone (B), cortisol (F), allopregnanolone (Allo-P5) and dihydroprogesterone (DHP).
RESULTS
The limits of quantification (LOQ) were 5 pg/mL for E2 and E1, 25 pg/mL for T, 50 pg/mL for A4 and 0.10 ng/mL for DHT, 17OHP5, P4, P5, AD, Adiol, DHEA, AlloP5 and 0.20 ng/mL for 17OHP4, 3α diol, 3β diol, DHP, 0.25 ng/mL for B and 1 ng/mL for F. Accuracy, precision, reproducibility and recovery were within acceptable limits for bioanalytical method validation. The method is illustrated in human and mouse, male and female serum.
CONCLUSIONS
The presented method is sufficiently sensitive, specific and reproducible to meet the quality criteria for routine laboratory application for accurate quantitation of 18 steroid concentrations in male and female serum from humans or mice for the purpose of profiling androgen synthesis and metabolism pathways.
PubMed: 34841072
DOI: 10.1016/j.clinms.2018.12.003 -
Steroids Dec 2020Steroid hormone levels in hair reflect the integrated values (average values) of hormone secretion over the past few months. We have used a method to evaluate diseases...
Steroid hormone levels in hair reflect the integrated values (average values) of hormone secretion over the past few months. We have used a method to evaluate diseases and chronic stress, discrimination of banned drug use, and so on. In contrast, the hair analysis methods reported so far required at least 10 mg (about 50 to 100 hair strands) of hair to analyze multiple steroid hormones from the same sample. Here, we developed a new method for measuring steroid hormones in hair by liquid chromatography-tandem mass spectrometry, which identifies multiple steroid hormones from 5 to 10 (about 1 mg) hair strands. Ten steroid hormones (cortisol, cortisone, testosterone, dihydrotestosterone, dehydroepiandrosterone, androstenedione, progesterone, pregnenolone, androstenediol and estradiol) covering from sex hormones to stress hormones were derivatized and measured by four different measuring systems. The method showed good linearity for all steroids with correlation coefficients of 0.999 or more. The accuracy and precision of intra- and inter-assay ranged from 96.0 to 106.4% and 4.8 to 8.1% for intra-assay, and from 96.9 to 104.9% and 6.9 and 10.6% for inter-assay, respectively. A mixed solution containing 0.1 M trifluoroacetic acid and 50% acetonitrile was used to extract hair and to enhance the cortisol extraction efficiency approximately twice compared to the previously reported extraction with methanol. This method has the potential to clarify the relationship between steroid hormone levels and diseases that show alopecia such as chronic stress and androgenetic alopecia.
Topics: Chromatography, Liquid; Gonadal Steroid Hormones; Hair; Humans; Limit of Detection; Male; Reproducibility of Results; Steroids; Tandem Mass Spectrometry
PubMed: 32976917
DOI: 10.1016/j.steroids.2020.108732 -
Hormones and Behavior Mar 2022In male vertebrates, testosterone is generally known to coordinate reproductive trade-offs, in part by promoting the transition to the next reproduction at the expense...
In male vertebrates, testosterone is generally known to coordinate reproductive trade-offs, in part by promoting the transition to the next reproduction at the expense of current parental care. The role of testosterone in reproductive transitions has been little tested in female vertebrates, especially in mammals. The present study sought to fill this gap, by first undertaking an experimental study, in which we identified DHT, androstenediol, and in particular etiocholanolone, as fecal androgen metabolites which reflect serum testosterone concentration in female rhesus macaques (Macaca mulatta). Using concentrations of fecal etiocholanolone as proxy for circulating testosterone, we then conducted a field study on 46 free-ranging rhesus macaques of Cayo Santiago, Puerto Rico, to test if testosterone mediates the trade-off between reproductive transition (a higher chance of reproducing in the next year) and current reproduction (providing more care to current offspring). While the evidence for testosterone was weak, the testing of fecal immunoreactive estrogen metabolites suggested a potential role of estrogen in reproductive trade-offs. We found large individual differences in fecal etiocholanolone concentrations during the early postpartum period that were unexplained even after accounting for sociodemographic factors such as age and dominance rank. Further investigation is needed to understand this variation. Our study suggests that the actions of testosterone in females may not have evolved to fulfil the same role in primate reproductive transitions as it does in males, and we encourage more studies to consider the function of testosterone in reproductive behaviors and life history transitions in females of mammalian taxa.
Topics: Animals; Estrogens; Etiocholanolone; Female; Macaca mulatta; Male; Mammals; Reproduction; Testosterone
PubMed: 35149292
DOI: 10.1016/j.yhbeh.2022.105123 -
American Journal of Obstetrics and... Jul 2022Risk-reducing salpingo-oophorectomy is an effective ovarian cancer risk reduction strategy. However, bilateral oophorectomy has also been associated with increased...
BACKGROUND
Risk-reducing salpingo-oophorectomy is an effective ovarian cancer risk reduction strategy. However, bilateral oophorectomy has also been associated with increased long-term nonneoplastic sequelae, effects suggested to be mediated through reductions in systemic sex steroid hormone levels. Currently, it is unclear whether the postmenopausal ovary contributes to the systemic hormonal milieu or whether postmenopausal ovarian volume or other factors, such as body mass index and age, affect systemic hormone levels.
OBJECTIVE
We examined the impact of oophorectomy on sex steroid hormone levels in postmenopausal women. Furthermore, we explored how well ovarian volume measured by transvaginal ultrasound correlated with direct ovarian measures obtained during surgical pathology evaluation and investigated the association between hormone levels and ovarian volumes.
STUDY DESIGN
Postmenopausal women who underwent risk-reducing salpingo-oophorectomy (180 cases) or ovarian cancer screening (38 controls) enrolled in an international, prospective study of risk-reducing salpingo-oophorectomy and risk of ovarian cancer algorithm-based screening among women at increased risk of ovarian cancer (Gynecologic Oncology Group-0199) were included in this analysis. Controls were frequency matched to the cases on age at menopause, age at study entry, and time interval between blood draws. Ovarian volume was calculated using measurements obtained from transvaginal ultrasound in both cases and controls and measurements recorded in surgical pathology reports from cases. Serum hormone levels of testosterone, androstenedione, androstenediol, dihydrotestosterone, androsterone, dehydroepiandrosterone, estrone, estradiol, and sex hormone-binding globulin were measured at baseline and follow-up. Spearman correlation coefficients were used to compare ovarian volumes as measured on transvaginal ultrasound and pathology examinations. Correlations between ovarian volumes by transvaginal ultrasound and measured hormone levels were examined using linear regression models. All models were adjusted for age. Paired t tests were performed to evaluate individual differences in hormone levels before and after risk-reducing salpingo-oophorectomy.
RESULTS
Ovarian volumes measured by transvaginal ultrasound were only moderately correlated with those reported on pathology reports (Spearman rho [ρ]=0.42). The median time interval between risk-reducing salpingo-oophorectomy and follow-up for the cases was 13.3 months (range, 6.0-19.3), and the median time interval between baseline and follow-up for the controls was 12.7 months (range, 8.7-13.4). Sex steroid levels decreased with age but were not correlated with transvaginal ultrasound ovarian volume, body mass index, or time since menopause. Estradiol levels were significantly lower after risk-reducing salpingo-oophorectomy (percentage change, -61.9 post-risk-reducing salpingo-oophorectomy vs +15.2 in controls; P=.02), but no significant differences were seen for the other hormones.
CONCLUSION
Ovarian volumes measured by transvaginal ultrasound were moderately correlated with volumes directly measured on pathology specimens and were not correlated with sex steroid hormone levels in postmenopausal women. Estradiol was the only hormone that declined significantly after risk-reducing salpingo-oophorectomy. Thus, it remains unclear whether the limited post-risk-reducing salpingo-oophorectomy changes in sex steroid hormones among postmenopausal women impact long-term adverse outcomes.
Topics: Estradiol; Female; Gonadal Steroid Hormones; Humans; Ovarian Neoplasms; Postmenopause; Prospective Studies; Salpingo-oophorectomy
PubMed: 35216968
DOI: 10.1016/j.ajog.2022.02.022 -
The Journal of Clinical Endocrinology... Dec 2018Adrenarche refers to the rise of dehydroepiandrosterone sulfate (DHEA-S) associated with the development of a functional adrenal zona reticularis. Clinical features of... (Observational Study)
Observational Study
CONTEXT
Adrenarche refers to the rise of dehydroepiandrosterone sulfate (DHEA-S) associated with the development of a functional adrenal zona reticularis. Clinical features of adrenarche include onset of body odor, axillary hair, and pubic hair, which reflect increased androgen action. An early rise in adrenal androgens, or premature adrenarche (PremA), is a risk factor for adverse metabolic profiles in adolescence and adulthood. The bioactive androgens associated with adrenarche and PremA remain poorly understood. The adrenal gland is a potential source of testosterone (T) and the 11-oxygenated derivatives 11β-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT).
OBJECTIVE
The objective of this study was to characterize the adrenal androgen biome contributing to adrenarche and PremA.
PARTICIPANTS AND METHODS
With the use of mass spectrometry, 19 steroids including the 11-oxygenated derivatives of T were measured in sera obtained from girls with PremA (n = 37; 4 to 7 years) and age-matched girls (n = 83; 4 to 10 years).
RESULTS
In reference population girls, dehydroepiandrosterone, DHEA-S, androstenediol-3-sulfate, T, and 11KT all increased at the onset of adrenarche (6 to 8 years) and beyond (9 to 10 years) (P < 0.05 vs younger subjects 4 to 5 years). T, 11OHT, and 11KT were further elevated in PremA vs age-matched girls (P < 0.001). Circulating concentrations of 11KT during adrenarche and PremA exceeded those of T and 11OHT (11KT > T ≥ 11OHT). Androgen receptor activity and nuclear translocation studies demonstrated that 11KT is a potent androgen similar to T.
CONCLUSIONS
Our findings suggest that 11KT is the dominant bioactive androgen in children during adrenarche and PremA. Its androgenic capacity suggests that it may be responsible for the phenotypic changes seen in these phenomena.
Topics: Adrenarche; Androgens; Child; Child, Preschool; Cohort Studies; Dehydroepiandrosterone Sulfate; Female; Humans; Mass Spectrometry; Puberty, Precocious; Testosterone; Zona Reticularis
PubMed: 30137510
DOI: 10.1210/jc.2018-00736 -
Physiological Research 2015Steroids are important components in the pathophysiology of Alzheimer's disease (AD). Although their role has been studied, the corresponding metabolomic data is...
Steroids are important components in the pathophysiology of Alzheimer's disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5alpha-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD.
Topics: Aged; Alzheimer Disease; Biomarkers; Enzyme Activation; Female; Humans; Male; Sulfotransferases; Zona Reticularis
PubMed: 26680489
DOI: 10.33549/physiolres.933160 -
International Journal of Molecular... Nov 2021There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher... (Meta-Analysis)
Meta-Analysis
There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher production of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione/androstenediol seems especially present in autism. An encompassing literature analysis was performed, searching for altered androgens in children with autism and using preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Included were all studies published before 31 March 2021 found using the following electronic databases: PubMed, Google Scholar, Cochrane Library, Scopus, and TRIP. Eight studies with boys and three studies with girls where steroid hormone measurements were performed from either plasma, urine, or saliva were found and analyzed. Analyses were performed for DHEA(-S/-C), androstenedione/androstenediol, and testosterone. Effect sizes were calculated for each parameter between mean concentrations for children with autism versus healthy controls. Higher levels of androgens in autism were detected, with the majority of calculated effect sizes being larger than one. We found higher levels of the main testosterone precursors DHEA, androstenedione, and androstenediol, likely causing an additionally higher level of testosterone, and an increased 17, 20-lyase activity is therefore implied. Medications already used in PCOS such as metformin might be considered to treat hyperandrogenism in autism following further research.
Topics: Androgens; Androstenediol; Androstenedione; Autistic Disorder; Child; Child, Preschool; Dehydroepiandrosterone; Female; Humans; Hyperandrogenism; Lyases; Male; Saliva; Testosterone
PubMed: 34830216
DOI: 10.3390/ijms222212324 -
Clinical Endocrinology Jan 2021To delineate the role of gonadotropins in male androgen biosynthesis pathways.
The role of gonadotropins in testicular and adrenal androgen biosynthesis pathways-Insights from males with congenital hypogonadotropic hypogonadism on hCG/rFSH and on testosterone replacement.
OBJECTIVE
To delineate the role of gonadotropins in male androgen biosynthesis pathways.
DESIGN
Case-control study.
PATIENTS AND MEASUREMENTS
Twenty five males with congenital hypogonadotropic hypogonadism (CHH) underwent hCG/rFSH and testosterone treatment sequentially. Serum steroid hormone profiles (testosterone precursors and metabolites) on both replacement regimens were analysed, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared to those of healthy controls, matched by age, BMI and serum testosterone.
RESULTS
On testosterone replacement, serum concentrations of the classic Δ4 pathway hormones progesterone and 17-hydroxy-progesterone (17-OHP), and the marker steroid of an alternative pathway of testosterone synthesis (androstenediol) were decreased, compared to controls. Androstanediol, a marker of the backdoor pathway of dihydrotestosterone (DHT) synthesis, was increased. 17-OH-pregnenolone, androstenedione and DHEAS (Δ5 pathway), three 11-oxygenated C19 androgens (11-keto-A4, 11-keto-T and 11-keto-DHT) and the testosterone (T) metabolites DHT and 17ß-oestradiol (E2) were similar to controls. On gonadotropin replacement, 17-OHP, 17-OH-pregnenolone, DHEAS and androstenedione, as well as DHT, androstenediol, and all 11-oxygenated C19 androgens were normal. Progesterone (Δ4 pathway) was slightly decreased, and androstanediol (backdoor DHT pathway) and E2 (T metabolite) were increased.
CONCLUSIONS
In males with CHH, serum steroid hormone profiles resemble those of healthy men, if hCG/rFSH is used for substitution. Gonadotropins contribute to steroid hormone production along the classic Δ4 pathway and co-activate an alternative pathway of testosterone biosynthesis via androstenediol. Backdoor DHT biosynthesis, Δ5 17-OH-pregnenolone, DHEA(S) and androstenedione synthesis and 11-oxygenated C19 androgen production are activated independently of gonadotropins. The androgen replacement modality used for treatment of hypogonadal males with absent or reduced endogenous LH/FSH secretion may impact on long-term health and quality of life.
Topics: Androgens; Case-Control Studies; Chromatography, Liquid; Gonadotropins; Humans; Hypogonadism; Male; Quality of Life; Tandem Mass Spectrometry; Testosterone
PubMed: 32871622
DOI: 10.1111/cen.14324 -
Menopause (New York, N.Y.) Dec 2015
Topics: Androstenediol; Androstenediols; Dehydroepiandrosterone; Endometrium; Female; Humans
PubMed: 26554883
DOI: 10.1097/GME.0000000000000558