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The Journal of Clinical Endocrinology... Sep 2022There is a lack of knowledge on longitudinal sex steroid patterns during infancy, especially for boys born preterm or with low birth weight (LBW).
CONTEXT
There is a lack of knowledge on longitudinal sex steroid patterns during infancy, especially for boys born preterm or with low birth weight (LBW).
OBJECTIVE
To find out whether LBW boys have a disturbed sex steroid profile during infancy.
DESIGN AND SETTING
Population-based longitudinal study performed at Sahlgrenska University Hospital, Gothenburg, Sweden.
PARTICIPANTS
Ninety-eight singleton boys (47 LBW) born at gestational age 32.0 to 36.9 weeks were included. Because of dropout, 83 of the boys were still in the study at 10 months' corrected age.
MAIN OUTCOME MEASURES
Serum androgen and estrogen concentrations were analyzed by gas chromatography-tandem mass spectrometry and IGF-I was determined with radioimmunoassay in umbilical cord and at 0, 2, 5, and 10 months' corrected age.
RESULTS
Serum levels of androstenedione, estrone, and estradiol declined gradually from birth to 10 months corrected age. In both LBW boys and their counterparts, a surge was seen at 2 months' corrected age (3 months' chronological age) for testosterone, median (range) 6.5 (2.0-18.9) nmol/L, and in dihydrotestosterone 1.2 (0.4-4.3) nmol/L. At birth, LBW boys had higher median testosterone (0.7 vs 0.4 nmol/L, P = 0.019), and at 0 months' corrected age, both had higher testosterone (5.7 vs 3.5 nmol/L, P = 0.003) and dihydrotestosterone (1.2 vs 0.9 nmol/L, P = 0.006) than their counterparts. At 10 months' corrected age, catch-up in weight SD score from birth correlated with testosterone (rho = 0.27, P = 0.044) and androstenedione (rho = 0.29, P = 0.027).
CONCLUSIONS
Moderately to late preterm LBW boys showed a disturbed sex hormone profile, with elevated concentrations of androgens in early infancy.
Topics: Androgens; Androstenedione; Birth Weight; Dihydrotestosterone; Estradiol; Estrogens; Estrone; Female; Humans; Infant; Infant, Newborn; Insulin-Like Growth Factor I; Longitudinal Studies; Male; Testosterone
PubMed: 35972993
DOI: 10.1210/clinem/dgac477 -
Journal of Veterinary Diagnostic... May 2022Analysis of steroid and thyroid hormones is often performed in blood serum. Occasionally though, plasma samples are submitted in lieu of serum for exotic species such as...
Analysis of steroid and thyroid hormones is often performed in blood serum. Occasionally though, plasma samples are submitted in lieu of serum for exotic species such as tigers. However, blood tube anticoagulants may affect hormone values. We compared serum and heparin plasma results for 7 hormones in tigers. Serum and plasma samples were collected from 25 tigers and analyzed for progesterone, 17-hydroxyprogesterone, cortisol, androstenedione, testosterone, estradiol, and thyroxine. Using Lin concordance correlation, serum and heparin plasma measures agreed for all hormones except cortisol. However, Passing-Bablok regression only found agreement between serum and heparin plasma measures for androstenedione, testosterone, and estradiol. Median values between the 2 sample types were significantly ( < 0.05) different for progesterone, 17-hydroxyprogesterone, cortisol, and thyroxine. Our results suggest that, for the aforementioned hormones, serum and heparin plasma values may not always be comparable.
Topics: 17-alpha-Hydroxyprogesterone; Androstenedione; Animals; Estradiol; Heparin; Hydrocortisone; Progesterone; Serum; Steroids; Testosterone; Thyroid Hormones; Thyroxine; Tigers
PubMed: 35404190
DOI: 10.1177/10406387221090538 -
Human Reproduction (Oxford, England) May 2023What are the changes in serum concentration of total and cleaved anti-Muüllerian hormone (AMH) molecular forms and of androgens before and throughout pregnancy in women...
STUDY QUESTION
What are the changes in serum concentration of total and cleaved anti-Muüllerian hormone (AMH) molecular forms and of androgens before and throughout pregnancy in women with and without polycystic ovary syndrome (PCOS) in a longitudinal follow-up investigation?
SUMMARY ANSWER
Serum levels of total and cleaved AMH are higher from preconception to the third trimester of pregnancy in women with PCOS as compared to controls, whereas testosterone and androstenedione levels are higher in women with PCOS than in control women before pregnancy and during the second and third trimester of pregnancy.
WHAT IS KNOWN ALREADY
Cross-sectional or partial longitudinal studies have shown higher AMH and androgen levels in pregnant women with PCOS as compared with non-PCOS women. To date, no complete longitudinal dynamic monitoring of the circulating forms of AMH and androgens from pre-conception to the third trimester of pregnancy have compared women with and without PCOS.
STUDY DESIGN, SIZE, DURATION
This systematic prospective quarterly longitudinal monocentric study was a comparative follow-up of 30 women with PCOS and 29 controls before and during pregnancy from April 2019 to July 2022.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Women aged 18-43 years with a pre-conception measurement of AMH were included during the first trimester of a singleton pregnancy. The PCOS group was defined according to the Rotterdam diagnostic criteria. The control group patients included in the study had normal ovarian reserves. Circulating total and cleaved AMH, and serum estradiol, LH, and androgen levels were measured during the first, second, and third trimester of pregnancy in all study participants.
MAIN RESULTS AND THE ROLE OF CHANCE
Before pregnancy, patients with PCOS had higher levels of AMH than controls. The total and cleaved AMH forms were significantly higher in women with PCOS than controls from pre-conception to the third trimester of pregnancy (all P < 0.001). Androgens (total testosterone and androstenedione) were higher in women with PCOS than controls from mid-pregnancy onwards.
LIMITATIONS, REASONS FOR CAUTION
Our control population was a population of infertile women with no ovarian problems but most of them had undergone ART treatments to achieve pregnancy.
WIDER IMPLICATIONS OF THE FINDINGS
These results strengthen the hypothesis that gestational hyperandrogenism as well as exposure to elevated AMH levels in utero could be driving forces predisposing female progeny to develop PCOS.
STUDY FUNDING/COMPETING INTEREST(S)
Funding was provided by INSERM, France (grant number U1172) and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program, ERC-2016-CoG to P.G. grant agreement n° 725149/REPRODAMH. The authors have nothing to declare.
TRIAL REGISTRATION NUMBER
NCT03483792.
Topics: Female; Humans; Pregnancy; Polycystic Ovary Syndrome; Androgens; Androstenedione; Longitudinal Studies; Prospective Studies; Cross-Sectional Studies; Infertility, Female; Anti-Mullerian Hormone; Testosterone
PubMed: 36921289
DOI: 10.1093/humrep/dead050 -
Proceedings of the National Academy of... Oct 2022, an opportunistic pathogen responsible for pulmonary infections, contains genes predicted to encode two steroid catabolic pathways: a cholesterol catabolic pathway...
, an opportunistic pathogen responsible for pulmonary infections, contains genes predicted to encode two steroid catabolic pathways: a cholesterol catabolic pathway similar to that of and a 4-androstenedione (4-AD) catabolic pathway. Consistent with this prediction, grew on both steroids. In contrast to , RHA1, and other Actinobacteria, the cholesterol and 4-AD catabolic gene clusters of the complex lack genes encoding HsaD, the -cleavage product (MCP) hydrolase. However, ATCC 19977 harbors two homologs elsewhere in its genome. Only one of the encoded enzymes detectably transformed steroid metabolites. Among tested substrates, HsaD and HsaD of had highest substrate specificities for MCPs with partially degraded side chains thioesterified with coenzyme A (/ = 1.9 × 10 and 5.7 × 10 mMs, respectively). Consistent with a dual role in cholesterol and 4-AD catabolism, HsaD also transformed nonthioesterified substrates efficiently, and a Δ mutant of grew on neither steroid. Interestingly, both steroids prevented growth of the mutant on acetate. The Δ mutant of excreted cholesterol metabolites with a fully degraded side chain, while the corresponding RHA1 mutant excreted metabolites with partially degraded side chains. Finally, the Δ mutant was not viable in macrophages. Overall, our data establish that the cholesterol and 4-AD catabolic pathways of are unique in that they converge upstream of where this occurs in characterized steroid-catabolizing bacteria. The data further indicate that cholesterol is a substrate for intracellular bacteria and that cholesterol-dependent toxicity is not strictly dependent on coenzyme A sequestration.
Topics: Androstenedione; Cholesterol; Coenzyme A; Humans; Hydrolases; Mycobacterium abscessus
PubMed: 36161908
DOI: 10.1073/pnas.2207505119 -
The Journal of Clinical Endocrinology... Nov 2023Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in...
CONTEXT
Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in general populations.
OBJECTIVE
To investigate if a 2-year lifestyle intervention influences circulating androgen concentrations and sexual maturation in a general population of children.
METHODS
We conducted a 2-year physical activity and dietary intervention study in which 421 prepubertal and mostly normal-weight 6- to 9-year-old children were allocated either to a lifestyle intervention group (119 girls, 132 boys) or a control group (84 girls, 86 boys). The main outcome measures were serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone concentrations, and clinical adrenarchal and pubertal signs.
RESULTS
The intervention and control groups had no differences in body size and composition, clinical signs of androgen action, and serum androgens at baseline. The intervention attenuated the increase of DHEA (P = .032), DHEAS (P = .001), A4 (P = .003), and testosterone (P = .007) and delayed pubarche (P = .038) in boys but it only attenuated the increase of DHEA (P = .013) and DHEAS (P = .003) in girls. These effects of lifestyle intervention on androgens and the development of pubarche were independent of changes in body size and composition, but the effects of intervention on androgens were partly explained by changes in fasting serum insulin.
CONCLUSION
A combined physical activity and dietary intervention attenuates the increase of serum androgen concentrations and sexual maturation in a general population of prepubertal and mostly normal-weight children, independently of changes in body size and composition.
Topics: Child; Female; Humans; Male; Adrenarche; Androgens; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Puberty; Testosterone; Exercise; Diet, Healthy
PubMed: 37329220
DOI: 10.1210/clinem/dgad367 -
Journal of Clinical Research in... Jun 2022Since there is no gold standard laboratory variable for adjustment of treatment in congenital adrenal hyperplasia (CAH), the aim was to assess the use of a 4-hour...
OBJECTIVE
Since there is no gold standard laboratory variable for adjustment of treatment in congenital adrenal hyperplasia (CAH), the aim was to assess the use of a 4-hour profile of serum 17-hydroxyprogesterone (17-OHP) to determine the most appropriate sample time and level of 17-OHP in predicting the metabolic control and evaluate the role of sex hormone-binding globulin (SHBG) in hyperandrogenemia.
METHODS
This study included children with salt-wasting CAH. Measurements for 17-OHP and cortisol were made from samples obtained before and 1, 2, and 4 hours after the morning dose of hydrocortisone. Patients were designated to have poor metabolic control when androstenedione levels according to age and sex-specific reference intervals were high and annual height standard deviation score (SDS) changes were ≥0.5.
RESULTS
The study cohort was 16 children (9 girls) with a median age of 7-years old. Premedication 17-OHP levels were strongly correlated with 17-OHP levels 1, 2, and 4 hours after the morning dose (r=0.929, p<0.01; r=0.943, p<0.01; r=0.835, p<0.01, respectively). 17-OHP profiles (0, 1, 2, 4 hours) of poor (n=6) and good (n=10) metabolically controlled cases were similar. Among the patients with poor metabolic control, two cases had 17-OHP levels <2 ng/mL at all times. The remaining patients with poor metabolic control had median 17-OHP levels above 104 ng/mL, 82 ng/mL, 14 ng/mL, and 4 ng/mL, for baseline and 1, 2, and 4 hours, respectively. Differences between the poor and well-controlled group were androstenedione levels with respect to upper limit of normal [1.8 (1.5) and 0.5 (1.5) ng/mL, respectively p=0.03], annual change in height SDS [0.7 (0.2) and -0.03 (0.8) SDS, respectively, p=0.001], and daily hydrocortisone doses [7 (6) and 16 (8) mg/m/day, respectively, p=0.02]. Androstenedione and SHBG levels were negatively correlated in the pubertal children (r=-0.7, p=0.04).
CONCLUSION
We conclude that: (i) a 4-hour 17-OHP profile is not useful in predicting hyperandrogenemia; (ii) suppressed levels of 17-OHP do not always indicate overtreatment; (iii) reference intervals of 17-OHP for different time periods might be of importance; (iv) low hydrocortisone doses should be avoided; and (v) SHBG could be used in pubertal children as an indicator of hyperandrogenemia.
Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Androgens; Androstenedione; Body Height; Child; Female; Humans; Hydrocortisone; Male; Urogenital Abnormalities
PubMed: 34866371
DOI: 10.4274/jcrpe.galenos.2021.2021-9-17 -
The Journal of Clinical Endocrinology... Jan 2022Testicular adrenal rest tumors (TART) are a common complication in males with classic 21-hydroxylase deficiency (21OHD). TART are likely to contribute to the androgen... (Observational Study)
Observational Study
CONTEXT
Testicular adrenal rest tumors (TART) are a common complication in males with classic 21-hydroxylase deficiency (21OHD). TART are likely to contribute to the androgen excess in 21OHD patients, but a direct quantification of steroidogenesis from these tumors has not been yet done.
OBJECTIVE
We aimed to define the production of 11-oxygenated 19-carbon (11oxC19) steroids by TART.
METHODS
Using liquid chromatography-tandem mass spectrometry, steroids were measured in left (n = 7) and right (n = 4) spermatic vein and simultaneously drawn peripheral blood (n = 7) samples from 7 men with 21OHD and TART. For comparison, we also measured the peripheral steroid concentrations in 5 adrenalectomized patients and 12 age- and BMI-matched controls. Additionally, steroids were quantified in TART cell- and adrenal cell-conditioned medium, with and without adrenocorticotropic hormone (ACTH) stimulation.
RESULTS
Compared with peripheral blood from 21OHD patients with TART, the spermatic vein samples displayed the highest gradient for 11β-hydroxytestosterone (11OHT; 96-fold) of the 11oxC19 steroids, followed by 11-ketotestosterone (47-fold) and 11β-hydroxyandrostenedione (11OHA4; 29-fold), suggesting production of these steroids in TART. TART cells produced higher levels of testosterone and lower levels of A4 and 11OHA4 after ACTH stimulation compared with adrenal cells, indicating ACTH-induced production of testosterone in TART.
CONCLUSION
In patients with 21OHD, TART produce 11oxC19 steroids, but in different proportions than the adrenals. The very high ratio of 11OHT in spermatic vs peripheral vein blood suggests the 11-hydroxylation of testosterone by TART, and the in vitro results indicate that this metabolism is ACTH-sensitive.
Topics: Adrenal Glands; Adrenal Hyperplasia, Congenital; Adrenal Rest Tumor; Adult; Androstenedione; Case-Control Studies; Humans; Hydroxytestosterones; Male; Middle Aged; Steroid 21-Hydroxylase; Testicular Neoplasms; Testis; Testosterone; Young Adult
PubMed: 34390337
DOI: 10.1210/clinem/dgab598 -
European Journal of Medicinal Chemistry Aug 2021The synthesis of two isomeric testosterone dimers and an androstenedione dimer is reported. The design takes advantage of an efficient transformation of testosterone...
Innovative C-symmetric testosterone and androstenedione dimers: Design, synthesis, biological evaluation on prostate cancer cell lines and binding study to recombinant CYP3A4.
The synthesis of two isomeric testosterone dimers and an androstenedione dimer is reported. The design takes advantage of an efficient transformation of testosterone leading to the synthesis of the key diene, 7α-(buta-1,3-dienyl)-4-androsten-17β-ol-3-one, through an elimination reaction. It was found that in some instances the same reaction led to partial epimerization of the 17β-hydroxyl group into the 17α-hydroxyl group. The specific orientation of the hydroxyl function was confirmed by NMR spectroscopy. Capitalizing on this unforeseen side reaction, several dimers were assembled using an olefin metathesis reaction with Hoveyda-Grubbs catalyst. This led to the formation of two isomeric testosterone dimers with 17α-OH or 17β-OH (14α and 14β) as well as an androstenedione dimer (14). The new dimers and their respective precursors were tested on androgen-dependent (LNCaP) and androgen independent (PC3 and DU145) prostate cancer cells. It was discovered that the most active dimer was made of the natural hormone testosterone (14β) with an average IC of 13.3 μM. In LNCaP cells, 14β was ∼5 times more active than the antiandrogen drug cyproterone acetate (IC of 12.0 μM vs. 59.6 μM, respectively). At low concentrations (0.25-0.5 μM), 14α and 14β were able to completely inhibit LNCaP cell growth induced by testosterone or dihydrotestosterone. Furthermore, cross-reactivity of androgen-based dimers with sterol-metabolizing cytochrome P450 3A4 was explored and the results are disclosed herein.
Topics: Androstenedione; Antineoplastic Agents; Cell Proliferation; Cell Survival; Cytochrome P-450 CYP3A; Dimerization; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; Male; Molecular Structure; Prostatic Neoplasms; Recombinant Proteins; Structure-Activity Relationship; Testosterone; Tumor Cells, Cultured
PubMed: 33933755
DOI: 10.1016/j.ejmech.2021.113496 -
Molecules (Basel, Switzerland) Sep 2020The biotransformation of steroid compounds is a promising, environmentally friendly route to new pharmaceuticals and hormones. One of the reaction types common in the...
The biotransformation of steroid compounds is a promising, environmentally friendly route to new pharmaceuticals and hormones. One of the reaction types common in the metabolic fate of steroids is Baeyer-Villiger oxidation, which in the case of cyclic ketones, such as steroids, leads to lactones. Fungal enzymes catalyzing this reaction, Baeyer-Villiger monooxygenases (BVMOs), have been shown to possess broad substrate scope, selectivity, and catalytic performance competitive to chemical oxidation, being far more environmentally green. This study covers the biotransformation of a series of androstane steroids (epiandrosterone and androsterone) and androstene steroids (progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, 19-OH-androstenedione, testosterone, and 19-nortestosterone) by the cultures of filamentous fungus AM110. The transformation was monitored by GC and the resulting products were identified on the basis of chromatographic and spectral data. The investigated fungus carries out effective Baeyer-Villiger oxidation of the substrates. Interestingly, introduction of the 19-OH group into androstenedione skeleton has significant inhibitory effect on the BVMO activity, as the 10-day transformation leaves half of the 19-OH-androstenedione unreacted. The metabolic fate of epiandrosterone and androsterone, the only 5α-saturated substrates among the investigated compounds, is more complicated. The transformation of these two substrates combined with time course monitoring revealed that each substrate is converted into three products, corresponding to oxidation at C-3 and C-17, with different time profiles and yields.
Topics: Androstanes; Androstenedione; Androsterone; Biotransformation; Chromatography, Gas; Mixed Function Oxygenases; Nandrolone; Oxidation-Reduction; Penicillium; Substrate Specificity
PubMed: 32942593
DOI: 10.3390/molecules25184226 -
Biochemia Medica Jun 2023Immunoassays are the most common method in routine practice for measuring androgens in women. Study's aim was to establish new population specific indirect reference...
INTRODUCTION
Immunoassays are the most common method in routine practice for measuring androgens in women. Study's aim was to establish new population specific indirect reference intervals (RI) for dehydroepiandrostenedione sulphate (DHEAS) and for new androstenedione test available on automated Roche Cobas electrochemiluminescent immunoassay method.
MATERIALS AND METHODS
From extracted laboratory records, testosterone, sex hormone binding globulin and follicle-stimulating hormone were used as reference tests to exclude possibly diseased women. After the data selection steps, the study included 3500 subjects for DHEAS and 520 for androstenedione aged 20-45 years. To evaluate the need for age partitioning, we calculated standard deviation ratio and bias ratio. For each hormone, 90% and 95% RIs were calculated with appropriate statistical method.
RESULTS
Total age group (20-45 years) 95% RIs were: 2.77-11.50 µmol/L for DHEAS and 2.48-8.89 nmol/L for androstenedione. Age-stratified 95% RIs for DHEAS were: 3.65-12.76 µmol/L (20-25 years); 2.97-11.50 µmol/L (25-35 years) and 2.30-9.83 µmol/L (35-45 years). Age-stratified 95% RIs for androstenedione were: 3.02-9.43 nmol/L (20-30 years) and 2.23-7.75 nmol/L (30-45 years).
CONCLUSION
New RIs for DHEAS were slightly wider for age group 20-25 and 35-45, while the differences in the age group 25-35 years were more pronounced. Androstenedione RI showed significantly higher concentrations than the manufacturer's. Age-related decrease of androgens should be considered when calculating RIs. We propose population specific, age-stratified RIs for DHEAS and androstenedione on electrochemiluminescent method, which should improve test interpretation in women of reproductive age.
Topics: Female; Humans; Androgens; Androstenedione; Sulfates; Dehydroepiandrosterone Sulfate; Testosterone
PubMed: 37324111
DOI: 10.11613/BM.2023.020706