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Scientific Reports Feb 2024This study was conducted in two groups of girls with PCOS (polycystic ovary syndrome) categorized as slim (group N) and overweight-to-obese (group Ov/Ob). The study's...
This study was conducted in two groups of girls with PCOS (polycystic ovary syndrome) categorized as slim (group N) and overweight-to-obese (group Ov/Ob). The study's primary outcome was to assess the impact of a 12-week anti-inflammatory diet (AIDiet) intervention, without energy deficit, on daily diet quality improvement, evaluated according to the KIDMED index. The secondary outcome was improving inflammatory, redox, hormonal, and metabolic statuses. In the study, which was completed by 13 girls from the Ov/Ob group and 19 girls from the N group, a significant improvement in the mean KIDMED score was obtained. Moreover, the intervention significantly improves concentration of total antioxidant capacity (TAC), fasting insulin, and the homeostatic model assessment for insulin resistance (HOMA-IR) index, in the Ov/Ob group, while both groups experienced a reduction in the concentration of interleukin (IL)-1 and IL-6, tumour necrosis factor (TNF-α), and androstenedione. The AIDiet intervention effectively improved the quality of the subjects' diets, which was associated with the improvement of hormonal and immuno-metabolic markers. However, these changes in normal-weight patients were observed regardless of body weight reduction. ClinicalTrials.gov Identifier NCT04738409.
Topics: Female; Humans; Overweight; Polycystic Ovary Syndrome; Pilot Projects; Diet; Insulin; Insulin Resistance; Anti-Inflammatory Agents; Body Mass Index
PubMed: 38347150
DOI: 10.1038/s41598-024-54100-1 -
International Journal of Molecular... Jan 2024Estrogens play critical roles in embryonic development, gonadal sex differentiation, behavior, and reproduction in vertebrates and in several human cancers. Estrogens...
Estrogens play critical roles in embryonic development, gonadal sex differentiation, behavior, and reproduction in vertebrates and in several human cancers. Estrogens are synthesized from testosterone and androstenedione by the endoplasmic reticulum membrane-bound P450 aromatase/cytochrome P450 oxidoreductase complex (CYP19/CPR). Here, we report the characterization of novel mammalian CYP19 isoforms encoded by CYP19 gene copies. These CYP19 isoforms are all defined by a combination of mutations in the N-terminal transmembrane helix (E42K, D43N) and in helix C of the catalytic domain (P146T, F147Y). The mutant CYP19 isoforms show increased androgen conversion due to the KN transmembrane helix. In addition, the TY substitutions in helix C result in a substrate preference for androstenedione. Our structural models suggest that CYP19 mutants may interact differently with the membrane (affecting substrate uptake) and with CPR (affecting electron transfer), providing structural clues for the catalytic differences.
Topics: Animals; Female; Humans; Pregnancy; Amino Acids; Androstenedione; Aromatase; Estrogens; Mammals; Protein Isoforms; Protein Structure, Tertiary; Protein Structure, Secondary
PubMed: 38338720
DOI: 10.3390/ijms25031440 -
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