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Journal of Mid-life Health 2023The aim of this study was to examine the association between endogenous hormones and bone mineral density (BMD) in postmenopausal women.
AIM
The aim of this study was to examine the association between endogenous hormones and bone mineral density (BMD) in postmenopausal women.
MATERIALS AND METHODS
This was a cross-sectional study of 798 postmenopausal women aged 47-85 years. Data were collected on age, age at menopause, years since menopause, smoking status, body mass index, adiposity, BMD, physical activity, and Vitamin D supplementation. Measured hormonal parameters were: follicle-stimulating hormone (FSH), estradiol, testosterone, dehydroepiandrosterone sulfate, ∆4-androstenedione, cortisol, insulin-like growth factor-1, 25-hydroxyvitamin D, and parathormone (PTH) levels. BMD was measured at the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. A directed acyclic graph was used to select potential confounding variables.
RESULTS
Multivariable analysis showed significant associations between cortisol and femoral neck BMD (β: -0.02, 95% confidence interval [CI]: -0.03--0.00), and PTH with femoral neck BMD (β: -0.01, 95% CI: -0.02--0.01) and total hip BMD (β: -0.01, 95% CI: -0.01--0.00). Hormonal factors more likely associated with a higher risk of low BMD (osteopenia or osteoporosis) were FSH (odds ratio [OR]: 1.02, 95% CI: 1.01-1.03) and PTH (OR: 1.02, 95% CI: 1.01-1.04).
CONCLUSIONS
Higher cortisol and PTH levels were inversely associated with BMD. Postmenopausal women with higher FSH or PTH levels were likely to have low BMD.
PubMed: 38312770
DOI: 10.4103/jmh.jmh_115_23 -
Problemy Endokrinologii Jan 2024Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders requiring lifelong glucocorticoid replacement (GC) therapy. Lack of GC therapy leads to... (Review)
Review
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders requiring lifelong glucocorticoid replacement (GC) therapy. Lack of GC therapy leads to precocious puberty in boys, heterosexual development in girls, accelerated bone maturation and short final height in both sexes. In adolescence, the lack of GC therapy is the cause of menstrual disorders in girls and the development of TART in boys, as a result reducing the reproductive potential in both sexes. On the other hand, an overdose of GC leads to drug-induced Itsenko-Cushing's syndrome. In order to select adequate doses of GC in childhood and adolescence, multiple determinations of 17-hydroxyprogesterone, androstenedione, and testosterone in blood plasma, and thus multiple venous blood sampling are required. The blood sampling requires specially trained medical staff and can effect on the results due to stress reaction especially in young patients. Hence, the development and implementation of a non-invasive method for determining the steroid profile is extremely important in monitoring GC therapy in children. In addition, the currently used immunofluorescence assay cannot determine other adrenal steroids, has a high variation due to the «cross-reaction» of steroids that are similar in structure, which inflates the results. Unlike immunofluorescence assay, liquid chromatography and tandem mass spectrometry is more preferable method, since it is more specific and accurate. In this literature review, saliva presented as an alternative substrate and the non-invasive method for determining the steroid profile. This method can solve the above disadvantages, simplify and make more accurate the selection of GC therapy in patients with CAH, which is especially important in childhood.
Topics: Adolescent; Child; Female; Humans; Male; 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Glucocorticoids; Puberty, Precocious; Steroids
PubMed: 38311999
DOI: 10.14341/probl13328 -
Neuroscience Mar 2024Aggression is a social behavior that is critical for survival and reproduction. In adults, circulating gonadal hormones, such as androgens, act on neural circuits to...
Aggression is a social behavior that is critical for survival and reproduction. In adults, circulating gonadal hormones, such as androgens, act on neural circuits to modulate aggressive interactions, especially in reproductive contexts. In many species, individuals also demonstrate aggression before reaching gonadal maturation. Adult male song sparrows, Melospiza melodia, breed seasonally but maintain territories year-round. Juvenile (hatch-year) males aggressively compete for territory ownership during their first winter when circulating testosterone is low. Here, we characterized the relationship between the steroid milieu and aggressive behavior in free-living juvenile male song sparrows in winter. We investigated the effect of a 10 min simulated territorial intrusion (STI) on behavior and steroid levels in blood, 10 microdissected brain regions, and four peripheral tissues (liver, pectoral muscle, adrenal glands, and testes). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we quantified 12 steroids: pregnenolone, progesterone, corticosterone, 11-dehydrocorticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone, 17β-estradiol 17α-estradiol, estrone, and estriol. We found that juvenile males are robustly aggressive, like adult males. An STI increases progesterone and corticosterone levels in blood and brain and increases 11-dehydrocorticosterone levels in blood only. Pregnenolone, androgens, and estrogens are generally non-detectable and are not affected by an STI. In peripheral tissues, steroid concentrations are very high in the adrenals. These data suggest that adrenal steroids, such as progesterone and corticosterone, might promote juvenile aggression and that juvenile and adult songbirds might rely on distinct neuroendocrine mechanisms to support similar aggressive behaviors.
Topics: Humans; Animals; Male; Songbirds; Corticosterone; Progesterone; Chromatography, Liquid; Tandem Mass Spectrometry; Testosterone; Androgens; Aggression; Estradiol; Pregnenolone
PubMed: 38301739
DOI: 10.1016/j.neuroscience.2024.01.008 -
Ecotoxicology and Environmental Safety Feb 2024Androstenedione (ADSD) is one of the widely detected androgens in diverse aquatic environments. However, there were few reports on the molecular mechanism of Chlorella...
Androstenedione (ADSD) is one of the widely detected androgens in diverse aquatic environments. However, there were few reports on the molecular mechanism of Chlorella vulgaris exposure to ADSD. In our previous research, we have investigated the genes associated with chlorophyll metabolism in Chlorella vulgaris response to ADSD. In this study, we focus on continuously up-regulated genes to explore the mechanism underlying Chlorella vulgaris resistance to ADSD toxicity. Chlorella vulgaris was exposed to ADSD with five concentration gradients. The continuously up-regulated genes were enriched by Series Test of Cluster (STC) analysis and verified by qRT-PCR. Microalgae Super Oxidase Dimutase (SOD) and Microalgae Malonic dialdehyde (MDA), two indicators of oxidative stress, were determined by ELISA after exposure to ADSD. The results showed that ADSD can stimulate the production of extracellular polymeric substances (EPS) and lead to enlargement in the cell body of Chlorella vulgaris. In addition, steroid biosynthesis and oxidoreductase activity processes were consistently up-regulated upon exposure to ADSD. In conclusion, our study highlighted the crucial role of phenotypic modification, hormone synthesis, and redox mechanisms in protecting Chlorella vulgaris cells from the harmful effects of ADSD contamination.
Topics: Chlorella vulgaris; Androstenedione; Oxidation-Reduction; Oxidative Stress; Microalgae
PubMed: 38277974
DOI: 10.1016/j.ecoenv.2024.115996 -
Antioxidants (Basel, Switzerland) Dec 2023Leydig cells (LCs) play a pivotal role in male fertility, producing testosterone. Chromium (III) picolinate (CrPic), a contentious supplement with antidiabetic and...
Leydig cells (LCs) play a pivotal role in male fertility, producing testosterone. Chromium (III) picolinate (CrPic), a contentious supplement with antidiabetic and antioxidant properties, raises concerns regarding male fertility. Using a rodent LC line, we investigated the cytotoxicity of increasing CrPic doses. An insulin resistance (IR) model was established using palmitate (PA), and LCs were further exposed to CrPic to assess its antioxidant/antidiabetic activities. An exometabolome analysis was performed using H-NMR. Mitochondrial function and oxidative stress were evaluated via immunoblot. Steroidogenesis was assessed by quantifying androstenedione through ELISA. Our results uncover the toxic effects of CrPic on LCs even at low doses under IR conditions. Furthermore, even under these IR conditions, CrPic fails to enhance glucose consumption but restores the expression of mitochondrial complexes CII and CIII, alleviating oxidative stress in LCs. While baseline androgen production remained unaffected, CrPic promoted androstenedione production in LCs in the presence of PA, suggesting that it promotes cholesterol conversion into androgenic intermediates in this context. This study highlights the need for caution with CrPic even at lower doses. It provides valuable insights into the intricate factors influencing LCs metabolism and antioxidant defenses, shedding light on potential benefits and risks of CrPic, particularly in IR conditions.
PubMed: 38247463
DOI: 10.3390/antiox13010040 -
Chemico-biological Interactions Feb 2024In patients with prostate carcinoma as well as in some other cancer types, the reduction of testosterone levels is desired because the hormone stimulates cancer cell...
In patients with prostate carcinoma as well as in some other cancer types, the reduction of testosterone levels is desired because the hormone stimulates cancer cell growth. One molecular target for this goal is the inhibition of 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3), which produces testosterone from its direct precursor androstenedione. Recent research in this field is trying to harness photopharmacological properties of certain compounds so that the inhibitory effect could be turned on and off by irradiation. Seven new light-switchable diazocines were investigated with regard to their inhibition of 17βHSD3. For this purpose, transfected HEK-293 cells and isolated microsomes were treated with the substrate and the potential inhibitors with and without irradiation for an incubation period of 3 or 5 h. The amount of generated testosterone was measured by UHPLC and compared between samples and control as well as between irradiated and non-irradiated samples. There was no significant difference between samples with and without irradiation. However, four of the seven diazocines led to a significantly lower testosterone production both in cell and in microsome assays. In some of the irradiated samples, a partial destruction of the diazocines was observed, indicated by an additional UHPLC peak. However, the influence on the inhibition is negligible, because the majority of the substance remained intact. In conclusion, new inhibitors of 17βHSD3 have been found, but so far without the feature of a light switch, since the configurational alteration of the diazocines by irradiation did not lead to a change in bioactivity. Further modification might help to find a light-switching molecule that inhibits only in one configuration.
Topics: Male; Humans; Testosterone; HEK293 Cells; Prostatic Neoplasms; 17-Hydroxysteroid Dehydrogenases; Androstenedione
PubMed: 38244963
DOI: 10.1016/j.cbi.2024.110872 -
Journal of the Endocrine Society Jan 2024Androgen levels are generally measured in serum samples, but urine may be a more feasible option, especially in children, as it is a noninvasive alternative.
CONTEXT
Androgen levels are generally measured in serum samples, but urine may be a more feasible option, especially in children, as it is a noninvasive alternative.
OBJECTIVE
To assess the correlations of 10 urinary androgen metabolites with 4 serum androgens [dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, and total and free testosterone] and assess if their correlations differ by participant characteristics.
METHODS
Our study consisted of 44 girls, ages 6-13, who participated in the New York site of the LEGACY Girls Study and had both serum and urine samples collected at the same visit. We performed Pearson's correlation coefficient tests between 4 serum and 10 individual urinary metabolite measures and their sum. We examined the influence of participant characteristics on the magnitude and direction of the correlations.
RESULTS
The summed urinary metabolite measures had the highest correlation with free testosterone in serum (global sum, r = 0.83) and correlated least with DHEA-S in serum (global sum, r = 0.64). The correlation between individual urinary metabolites and serum androgens ranged from 0.08 to 0.84.Two 11-oxygenated urinary metabolites (5α-androstane-3α-ol-11,17-dione5β-androstane-3α,11β-diol-17-one) were weakly correlated with all serum androgens. Participant age, weight, height, waist:hip ratio, and pubic hair growth stage changed the correlations between urinary and serum androgens measures between 10% and 213%.
CONCLUSION
The sum of urinary androgen metabolites was a good marker of circulating androstenedione, testosterone, and free testosterone. Individual urinary metabolites provide additional information about the metabolic processes of disease development compared to the antecedent serum androgens.
PubMed: 38234314
DOI: 10.1210/jendso/bvad161 -
Journal of the Endocrine Society Jan 2024Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and...
INTRODUCTION
Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis.
METHODS
Data were extracted from the CALICO multisite PCOS database. Clinical data collected at the time of diagnosis were available in 354 patients (81% with obesity) from 7 academic centers. Patients with body mass index (BMI) < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G.
RESULTS
Reproductive phenotypes differed between the groups, with LN-G having higher total testosterone, androstenedione, and LH levels, while OB-G had lower sex hormone binding globulin (SHBG) and higher free testosterone. Metabolic profiles differed as expected, with OB-G having higher hemoglobin A1c, alanine aminotransferase, and serum triglycerides and more severe acanthosis nigricans.
CONCLUSION
LN-G with PCOS had a distinct reproductive phenotype characterized by increased LH, total testosterone, and androstenedione levels, suggesting neuroendocrine-mediated ovarian androgen production. In contrast, phenotypes in OB-G suggest hyperandrogenemia is primarily driven by insulin resistance with low SHBG levels. These observations support the existence of distinct metabolic and reproductive subtypes in adolescent PCOS characterized by unique mechanisms for hyperandrogenemia.
PubMed: 38213910
DOI: 10.1210/jendso/bvad169 -
Clinical Chemistry and Laboratory... May 2024Current liquid chromatography-tandem mass spectrometry (LC-MS/MS) applications for circulating androgen measurements are technically diverse. Previously, variable... (Comparative Study)
Comparative Study
OBJECTIVES
Current liquid chromatography-tandem mass spectrometry (LC-MS/MS) applications for circulating androgen measurements are technically diverse. Previously, variable results have been reported for testosterone. Data are scarce for androstenedione and absent for dehydroepiandrosterone sulfate (DHEAS). We assessed the agreement of androstenedione, DHEAS and testosterone LC-MS/MS measurements among nine European centers and explored benefits of calibration system unification.
METHODS
Androgens were measured twice by laboratory-specific procedures in 78 patient samples and in EQA materials. Results were obtained by and external calibration. Intra- and inter-laboratory performances were valued.
RESULTS
Intra-laboratory CVs ranged between 4.2-13.2 % for androstenedione, 1.6-10.8 % for DHEAS, and 4.3-8.7 % and 2.6-7.1 % for female and male testosterone, respectively. Bias and trueness in EQA materials were within ±20 %. Median inter-laboratory CV with vs. external calibration were 12.0 vs. 9.6 % for androstenedione (p<0.001), 7.2 vs. 4.9 % for DHEAS (p<0.001), 6.4 vs. 7.6 % for female testosterone (p<0.001) and 6.8 and 7.4 % for male testosterone (p=0.111). Median bias vs. all laboratory median with and external calibration were -13.3 to 20.5 % and -4.9 to 18.7 % for androstenedione, -10.9 to 4.8 % and -3.4 to 3.5 % for DHEAS, -2.7 to 6.5 % and -11.3 to 6.6 % for testosterone in females, and -7.0 to 8.5 % and -7.5 to 11.8 % for testosterone in males, respectively.
CONCLUSIONS
Methods showed high intra-laboratory precision but variable bias and trueness. Inter-laboratory agreement was remarkably good. Calibration system unification improved agreement in androstenedione and DHEAS, but not in testosterone measurements. Multiple components, such as commutability of calibrators and EQA materials and internal standard choices, likely contribute to inter-laboratory variability.
Topics: Androstenedione; Testosterone; Humans; Tandem Mass Spectrometry; Calibration; Male; Female; Chromatography, Liquid; Dehydroepiandrosterone Sulfate; Middle Aged; Liquid Chromatography-Mass Spectrometry
PubMed: 38205643
DOI: 10.1515/cclm-2023-1138 -
Frontiers in Microbiology 2023Limited numbers of CYPs have been reported to work naturally as peroxygenases. The peroxide shunt pathway can be efficiently used as an alternative for the NAD(P)H and...
Limited numbers of CYPs have been reported to work naturally as peroxygenases. The peroxide shunt pathway can be efficiently used as an alternative for the NAD(P)H and reductase systems, particularly in high hydrogen peroxide (HO) resistance CYPs. We reported the structural and biochemical features of CYP105D18 peroxygenase for its high HO tolerance capacity. Q348 was a crucial residue for the stability of CYP105D18 during the exposure to HO. In addition, the role of the hydrophilic amino acid T239 from the I helix for peroxygenation and regiospecificity toward testosterone was investigated. Interestingly, T239E differs in product formation from wild type, catalyzing testosterone to androstenedione in the presence of HO. The other variant, T239A, worked with the Pdx/Pdr system and was unable to catalyze testosterone conversion in the presence of HO, suggesting the transformation of peroxygenase into monooxygenase. CYP105D18 supported the alternative method of HO used for the catalysis of testosterone. The use of the same concentration of urea hydrogen peroxide adducts in place of direct HO was more efficient for 2β-hydroxytestosterone conversion. Furthermore, HO generation using GOx/glucose system enhanced the catalytic efficiency (/) for wild type and F184A by 1.3- and 1.9-fold, respectively, compared to direct use of HO The engineering of CYP105D18, its improved peroxygenase activity, and alteration in the product oxidation facilitate CYP105D18 as a potential candidate for biotechnological applications.
PubMed: 38149268
DOI: 10.3389/fmicb.2023.1296202