Serum Steroid Concentrations Research Articles

Neonatal reference intervals for serum steroid hormone concentrations measured by LC-MS/MS.

Congenital adrenal hyperplasia (CAH) is a rare, inherited disorder of adrenal steroid synthesis. In many countries it is part of the neonatal screening program enabling early diagnosis and treatment. In case of an abnormal neonatal screening result or when other differences of sexual development (DSD) are suspected, measurement of serum steroid hormones using liquid chromatography coupled to mass spectrometry (LC-MS/MS) is needed for further diagnosis. However, reliable age- and sex-specific reference intervals (RIs) for serum steroid hormones during the neonatal period are missing. We therefore aimed to establish LC-MS/MS based RIs for serum steroid hormones in neonates. Serum was obtained from healthy term neonates at two time points: 130 samples at day 3-8 (T1, time of the neonatal screening) and 126 samples at day 13-15 (T2,two weeks old). Concentrations of cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, 11-deoxycorticosterone, testosterone, androstenedione, and 17-hydroxyprogesterone (17-OHP) were measured using LC-MS/MS. RIs (in nmol/L) were established for T1 and T2: cortisone (19.3-215;18.0-212), cortisol (10.0-407;8.4-446), corticosterone (<31;<50), 11-deoxycortisol (0.73-4.6;0.70-3.6), 17-OHP (<4.9;<5.1), androstenedione (0.3-1.8;0.3-2.7), 11-deoxycorticosterone (<0.2;<0.2), and 21-deoxycortisol (<1;<1), respectively. Testosterone differed between boys and girls: RIs at T1 and T2 for boys were 0.27-4.3 and 0.63-13.9, and for girls<0.30 and <0.47, respectively. We established LC-MS/MS based RIs for cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, 11-deoxycorticosterone, testosterone, androstenedione, and 17-OHP in neonates in the first and second week of life.

Improving the Determination of Carbon Isotope Ratios of Endogenous Steroids Found in Human Serum.

The determination of serum concentrations of testosterone (T) and 4-androstenedione (A4) was implemented into the steroidal module of the Athlete Biological Passport in 2023. Monitoring T, A4, and the ratio of T/A4 in a longitudinal manner enables the detection of the misuse of low-dose T administrations especially in female athletes, whereas urinary markers of the steroid profile may not be influenced significantly. In contrast to the urinary steroid profile, knowledge on confounding factors regarding serum concentrations of T and A4 is yet comparably scarce, and corroborating exogenous sources of the target analytes by isotope ratio mass spectrometry (IRMS) is desirable. In a recent study, it was demonstrated that carbon isotope ratios (CIRs) of serum steroids can be determined if analyte concentrations permit. The therein-employed method utilized 2D-GC/IRMS, and only a limited number of potential endogenous reference compounds were available. The here-presented approach uses complementary analyte purification strategies, addressing previous limitations. A high-performance liquid chromatography cleanup was developed and fully validated for serum steroids in order to enable all doping control laboratories to potentially implement this method alongside existing protocols for urinary steroids. Besides the already-investigated endogenous steroids cholesterol, dehydroepiandrosterone sulfate, androsterone sulfate, and epiandrosterone sulfate, two additional steroids were included in the test menu, namely, pregnenolone sulfate and 5-androstene-3β,17β-diol sulfate. Serum steroid concentrations down to 25 ng/mL were found to allow robust CIR determinations, and a reference population encompassing 124 male and female athlete samples was investigated to enable the calculation of population-based thresholds for all relevant steroid combinations.

Association between Disgust Sensitivity during Pregnancy and Endogenous Steroids: A Longitudinal Study.

The emotion of disgust protects individuals against pathogens, and it has been found to be elevated during pregnancy. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. This study aimed to assess the association between steroids and disgust sensitivity in pregnancy. Using a prospective longitudinal design, we analyzed blood serum steroid concentrations and measured disgust sensitivity via text-based questionnaires in a sample of 179 pregnant women during their first and third trimesters. We found positive correlations between disgust sensitivity and the levels of C19 steroids (including testosterone) and its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Additionally, positive correlations were observed with 5α/β-reduced C19 steroid metabolites in both trimesters. In the first trimester, disgust sensitivity was positively associated with 17-hydroxypregnanolone and with some estrogens. In the third trimester, positive associations were observed with cortisol and immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our findings show that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, with steroids which may be related to potential maternal-anxiety-related symptoms. This study highlights the complex relationship between hormonal changes and disgust sensitivity during pregnancy.

Association between secondhand smoke exposure and serum sex hormone concentrations among US female adults: a cross-sectional analysis using data from the National Health and Nutrition Examination Survey, 2013–2016

ObjectiveTo estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers).DesignCross-sectional analysis.SettingUS National Health and Nutrition Examination Survey, 2013–2016.Outcome...

Possibility of early pregnancy detection in alpacas (Vicugna pacos) based on fecal steroid hormone concentrations.

Early pregnancy detection in alpacas, whose breeding season is limited to the rainy season and has a long gestation period, is important for reproductive management. Conventional detection methods such as ultrasonography cannot be used to detect pregnancy before 30 days after mating. In this study, we examined the feasibility of using fecal steroid hormones as an early detection method in pregnant and non-pregnant alpacas. Fecal and blood samples were collected from pregnant and non-pregnant alpacas after mating. Progesterone (P4) and estradiol 17-β were extracted and quantified from blood and fecal samples. A positive correlation exists between the steroid hormones in serum and feces, indicating that serum steroid hormone concentrations can be estimated from fecal steroid hormones. Within 10days after mating, both pregnant and non-pregnant alpacas had fecal P4 concentrations greater than 1.0ng/mg dry matter (DM), but by 15 days after mating, fecal P4 concentrations decreased to the pre-mating concentration in non-pregnant alpacas. From 15 days after mating, non-pregnant alpacas had a low fecal P4 concentration (< 1ng/mg DM), whereas a high fecal P4 concentration indicated the possibility of pregnancy, suggesting that this test is clinically beneficial as a supportive test for pregnancy detection.

11-deoxycortisol positively correlates with T cell immune traits in physiological conditions

Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely unexplored. We conducted a systematic approach to examine the association between steroid hormones profile and immune traits in a cohort of 534 healthy volunteers. Serum concentrations of steroid hormones and their precursors (cortisol, progesterone, testosterone, androstenedione, 11-deoxycortisol and 17-OH progesterone) were determined by liquid chromatography-tandem mass spectrometry. Immune traits were evaluated by quantifying cellular composition of the circulating immune system and exvivo cytokine responses elicited by major human pathogens and microbial ligands. An independent cohort of 321 individuals was used for validation, followed by invitro validation experiments. We observed a positive association between 11-deoxycortisol and lymphoid cellular subsets numbers and function (especially IL-17 response). The association with lymphoid cellularity was validated in an independent validation cohort. Invitro experiments showed that, as compared to androstenedione and 17-OH progesterone, 11-deoxycortisol promoted T cell proliferation and Candida-induced Th17 polarization at physiologically relevant concentrations. Functionally, 11-deoxycortisol-treated T cells displayed a more activated phenotype (PD-L1high CD25high CD62Llow CD127low) in response to CD3/CD28 co-stimulation, and downregulated expression of T-bet nuclear transcription factor. Our findings suggest a positive association between 11-deoxycortisol and T-cell function under physiological conditions. Further investigation is needed to explore the potential mechanisms and clinical implications. Found in acknowledgements.

Serum steroid and thyroid hormone concentrations in healthy domestic male and female alpacas.

Alpacas are high quality fiber producing animals, kept for production purpose and as pets. Endocrine imbalances from adrenal glands, gonads, or thyroid gland may result in coat abnormalities in domestic animals and affect reproduction. Contrary to many domesticated animals, information on hormone concentrations in alpacas is scarce. The purpose of this study was to provide steroid and thyroid hormone values in domestic alpacas. Blood was collected from healthy male (35 intact, 2 castrated) and female (48 non-pregnant, 3 pregnant) alpacas from local farms in Tennessee. Adrenal, reproductive, and thyroid hormones were analyzed. There were no significant differences in median concentrations of progesterone, estradiol, thyroxine (T4), and triiodothyronine (T3) between intact male and female non-pregnant alpacas. Median concentrations of testosterone, androstenedione, 17-hydroxyprogesterone, and cortisol were significantly higher in intact male alpacas compared to female non-pregnant alpacas. This information provides adrenal, gonadal, and thyroid hormone concentrations in alpacas to help with diagnosis of endocrine disorders.

The effects of sex hormones during the menstrual cycle on knee kinematics.

The effects of the menstrual cycle and sex hormones on knee kinematics remain unclear. The purpose of the study was to investigate the effects of the menstrual cycle and serum sex hormone concentrations on knee kinematic parameters of the 90°cutting in female college soccer athletes. Three female college soccer teams (53 subjects) participated in the study. During the first menstrual cycle, a three-step method was used to exclude subjects with anovulatory and luteal phase-deficient (LPD) (12 subjects). The subjects' menstrual cycle was divided into the menstrual phase, late-follicular phase, ovulatory phase, and mid-luteal phase (group 1, 2, 3, 4). In each phase of the second menstrual cycle, we used a portable motion analysis system to enter the teams and tested the sex hormones concentrations and knee kinematics parameters in three universities in turn. We found that subjects had a lower maximum knee valgus in group 4 compared with other groups. This meant that subjects had a lower biomechanical risk of non-contact anterior cruciate ligament (ACL) injury in the mid-luteal phase. There was no significant correlation between serum estrogen, progesterone concentration, and knee kinematic parameters. This meant that sex hormones did not have a protective effect. Future studies need to incorporate more factors (such as neuromuscular control, etc.) to investigate.

Association of serum cortisol and cortisone levels and risk of recurrence after endocrine treatment in breast cancer

Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may influence carcinogenesis, breast cancer growth, and response to therapy. Our aim was to examine whether serum steroid hormone concentrations could predict the risk of recurrence and treatment-related fatigue in patients with breast cancer. This study included 66 postmenopausal patients with estrogen receptor-positive breast cancer who underwent surgery, radiotherapy, and adjuvant endocrine treatment. Serum samples were collected at six different time points [before the start of radiotherapy (as baseline), immediately after radiotherapy, and then 3, 6, 12 months, and 7–12 years after radiotherapy]. Serum concentrations of eight steroid hormones (cortisol, cortisone, 17α-hydroxyprogesterone, 17β-estradiol, estrone, androstenedione, testosterone, and progesterone) were measured using a liquid chromatography–tandem mass spectrometry-based method. Breast cancer recurrence was defined as clinically proven relapse/metastatic breast cancer or breast cancer-related death. Fatigue was assessed with the QLQ-C30 questionnaire. Serum steroid hormone concentrations measured before and immediately after radiotherapy differed between relapse and relapse-free patients [(accuracy 68.1%, p = 0.02, and 63.2%, p = 0.03, respectively, partial least squares discriminant analysis (PLS-DA)]. Baseline cortisol levels were lower in patients who relapsed than in those who did not (p < 0.05). The Kaplan–Meier analysis showed that patients with high baseline concentrations of cortisol (≥ median) had a significantly lower risk of breast cancer recurrence than patients with low cortisol levels (<median) (p = 0.02). During follow-up, there was a decrease in cortisol and cortisone concentrations in relapse-free patients, whereas these steroid hormones increased in patients who relapsed. In addition, steroid hormone concentrations immediately after radiotherapy were associated with treatment-related fatigue (accuracy of 62.7%, p = 0.03, PLS-DA). However, baseline steroid hormone levels did not predict fatigue at 1 year or at 7–12 years. In conclusion, breast cancer patients with low baseline cortisol levels were more likely to experience recurrence. During follow-up, cortisol and cortisone levels decreased in relapse-free patients but increased in patients with recurrence. Thus, cortisol and cortisone may act as potential biomarkers indicating individual risk of recurrence.

Acute changes in serum and skeletal muscle steroids in resistance-trained men.

Resistance exercise can significantly increase serum steroid concentrations after an exercise bout. Steroid hormones are involved in the regulation of several important bodily functions (e.g., muscle growth) through both systemic delivery and local production. Thus, we aimed to determine whether resistance exercise-induced increases in serum steroid hormone concentrations are accompanied by enhanced skeletal muscle steroid concentrations, or whether muscle contractions per se induced by resistance exercise can increase intramuscular steroid concentrations. A counterbalanced, within-subject, crossover design was applied. Six resistance-trained men (26 ± 5 years; 79 ± 8 kg; 179 ± 10 cm) performed a single-arm lateral raise exercise (10 sets of 8 to 12 RM - 3 min rest between sets) targeting the deltoid muscle followed by either squat exercise (10 sets of 8 to 12 RM - 1 min rest) to induce a hormonal response (high hormone [HH] condition) or rest (low hormone [LH] condition). Blood samples were obtained pre-exercise and 15 min and 30 min post-exercise; muscle specimens were harvested pre-exercise and 45 min post-exercise. Immunoassays were used to measure serum and muscle steroids (total and free testosterone, dehydroepiandrosterone sulfate, dihydrotestosterone, and cortisol; free testosterone measured only in serum and dehydroepiandrosterone only in muscle) at these time points. In the serum, only cortisol significantly increased after the HH protocol. There were no significant changes in muscle steroid concentrations after the protocols. Our study provides evidence that serum steroid concentration increases (cortisol only) seem not to be aligned with muscle steroid concentrations. The lack of change in muscle steroid after protocols suggests that resistance-trained individuals were desensitized to the exercise stimuli. It is also possible that the single postexercise timepoint investigated in this study might be too early or too late to observe changes. Thus, additional timepoints should be examined to determine if RE can indeed change muscle steroid concentrations either by skeletal muscle uptake of these hormones or the intramuscular steroidogenesis process.

Virgin coconut oil reverses behavioral phenotypes of letrozole-model of PCOS in Wistar rats via modulation of NRF2 upregulation

ObjectivesPolycystic ovarian syndrome (PCOS) is an endocrine disorder associated with insulin resistance, hyperandrogenism, and sub-infertility. Virgin coconut oil (VCO) has been reported to have health benefits, such as anti-inflammatory, anti-oxidant, and antiviral properties. This study investigated the effects of dietary VCO supplementation on memory and cognitive impairment in female rats with letrozole induced PCOS. MethodsThirty female rats were randomly divided into five groups. All rats except controls were treated with letrozole for 21 days to induce PCOS and were subsequently treated for 14 days with 10% VCO, clomiphene (CLO), or VCO + CLO. Three neurobehavioral tests were conducted: elevated plus maze, Y maze, and novel object recognition tests. ResultsOur results indicated statistically elevated serum concentrations of sex hormones in rats with PCOS, compared with the control and treated groups. In addition, all treated groups showed significant reversal of the low serum concentrations of catalase and down-regulated gene expression of Nrf2 in the hippocampus seen in the PCOS rats. In addition, gene expression of acetylcholine esterase was up-regulated in PCOS rats, and was statistically reverted in the VCO treated groups. ConclusionAnxiety-like behavior and impaired short-term memory were observed in PCOS rats; however, VCO supplementation reversed these effects by modulating the gene expression of Nrf2 and AchE.

Association between acrylamide exposure and sex hormones among premenopausal and postmenopausal women: NHANES, 2013-2016.

Acrylamide (AA) is a potential carcinogen that mainly comes from fried, baked and roasted foods, and Hb adducts of AA (HbAA) and its metabolite glycidamide (HbGA) are the biomarkers of its exposure. Increasing evidence suggests that AA is associated with various hormone-related cancers. This study aims to explore the association of HbAA and HbGA with female serum sex hormone concentrations. 942 women from the National Health and Nutrition Examination Survey cycles (2013-2016) were included in this cross-sectional study. The associations between HbAA or HbGA or HbGA/HbAA and sex hormones were assessed by the multiple linear regression. Further stratified analyses were conducted to figure out the effects of menopausal status, BMI and smoking status on sex hormone levels. Among all participants, 597 were premenopausal and 345 were postmenopausal. HbAA was positively associated with both two androgen indicators. Specifically, a ln-unit increase in HbAA was associated with 0.41ng/dL higher ln(total testosterone, TT) (95% CI 0.00, 0.27) and 0.14ng/dL higher ln(free testosterone) (95%CI 0.00, 0.28), respectively. However, HbGA concentrations had no association with sex hormones in the overall population. Additionally, HbGA/HbAA was negatively associated with TT and SHBG in the overall population as well as postmenopausal women. In stratified analysis, higher HbAA was associated with rising TT in postmenopausal women (β = 0.29, 95%CI 0.04, 0.53) and underweight/normal-weight women (β = 0.18, 95%CI 0.03, 0.33). Other indicators had no significant association detected in estradiol and sex hormone-binding globulin. Our results revealed that HbAA was positively associated with androgen concentrations, especially in postmenopausal and BMI < 25 women.

Quantitative assessment of breast cancer resistance protein during pregnancy in rabbits

Breast cancer resistance protein (BCRP,ABCG2) is an efflux transporter protein that transports various substrates from the cell to the extracellular space or organ cavities. The aim of this study was a complex assessment of the amount of BCRP during pregnancy in rabbits. The amount of BCRP in samples of the rabbit jejunum, liver, kidney, cerebral cortex, and placenta was determined by enzyme immunoassay, and in human hepatocellular carcinoma (HepG2) cells by the Western blot. To study the mechanisms involved in control of the dynamic BCRP levels during pregnancy, serum concentrations of sex hormones were investigated by radioimmunoassay and relative amounts of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in these organs were evaluated using the Western blot method. The putative role of CAR and PXR in regulation of the BCRP level by progesterone was evaluated in vitro experiments on HepG2 cells. It was found that amount of BCRP in the jejunum of pregnant rabbits was higher than in the placenta, liver, kidneys, and cerebral cortex. An increase in the amount of BCRP in the liver of rabbits was noted on the 21st day of pregnancy and a tendency to the increase was also detected on the 28th day; in the kidney and cerebral cortex increased BCRP levels were detected on the 28th day and 14th day of pregnancy, respectively, as compared with non-pregnant females. In vitro experiments with HepG2 cells have shown that the increase in the BCRP level is determined by the activating effect of progesterone on PXR.

Associations between urinary concentrations of bisphenols and serum concentrations of sex hormones among US. Males

BackgroundBisphenol A (BPA) exposure and its structural analogs (BPS and BPF) might cause endocrine alterations and adverse physiological effects. Few studies to date have directly explored the association between its structural analogs (BPS, BPF) and sex hormones in adult male participants. Therefore, we aimed to assess the associations between BPA, BPS, BPF, and sex hormones in American adult men.MethodsWe used data from the U.S. National Health and Nutrition Examination Survey 2011–2016. We excluded participants without data available on sex hormones and urinary bisphenols. Furthermore, participants consuming sex hormone medications were excluded. Multivariable regression models were performed to assess the association between bisphenols and sex hormones.ResultsIn this study, 2367 participants were included. Of 2367, in 1575 participants, the data on BPS and BPF were available. We found that a per unit increase in BPF was associated with 0.575 ng/dL higher total testosterone (TT) (Model 2: 95% CI: 0.047, 1.103, P = 0.033). However, there was no significant association between BPA or BPS and TT. Furthermore, increased BPA and BPS levels were associated with higher levels of sex hormone-binding globulin (SHBG) (Model 2: β = 0.364, 95% CI: 0.158, 0.571; β = 0.25, 95% CI: 0.071, 0.429, respectively). Additionally, participants in the highest BPA exposure quartile (quartile 4) had 4.072 nmol/L higher levels of SHBG than those in quartile 1 (Model 2: 95% CI: 0.746, 7.397, P = 0.017; P for trend =0.005). Both BPA and BPS were negatively associated with free testosterone (FT, nmol/L) after full adjustment (Model 2, β = − 0.01%, P = 0.0211, P = 0.0211; Model 2, β = − 0.01%, P = 0.0258, respectively). However, BPF was positively associated with FT (Model 2, β = 0.0029%, P = 0.0028).ConclusionOur study indicated that exposure to both BPA and its substitutions could alter sex hormone levels. This finding supports the possibility that human exposure to bisphenols at environmental levels might affect the endogenous hormone balance.

First-in-Class Small Molecule to Inhibit CYP11A1 and Steroid Hormone Biosynthesis.

Binding of steroid hormones to their cognate receptors regulates the growth of most prostate and breast cancers. We hypothesized that CYP11A inhibition might halt the synthesis of all steroid hormones, because CYP11A is the only enzyme that catalyses the first step of steroid hormone biosynthesis. We speculated that a CYP11A inhibitor could be administered safely provided that the steroids essential for life are replaced. Virtual screening and systematic structure-activity relationship optimization were used to develop ODM-208, the first-in-class, selective, nonsteroidal, oral CYP11A1 inhibitor. Safety of ODM-208 was assessed in rats and Beagle dogs, and efficacy in a VCaP castration-resistant prostate cancer (CRPC) xenograft mouse model, in mice and dogs, and in six patients with metastatic CRPC. Blood steroid hormone concentrations were measured using liquid chromatography-mass spectrometry. ODM-208 binds to CYP11A1 and inhibited its enzymatic activity. ODM-208 administration led to rapid, complete, durable, and reversible inhibition of the steroid hormone biosynthesis in an adrenocortical carcinoma cell model in vitro, in adult noncastrated male mice and dogs, and in patients with CRPC. All measured serum steroid hormone concentrations reached undetectable levels within a few weeks from the start of ODM-208 administration. ODM-208 was well tolerated with steroid hormone replacement. The toxicity findings were considered related to CYP11A1 inhibition and were reversed after stopping of the compound administration. Steroid hormone biosynthesis can be effectively inhibited with a small-molecule inhibitor of CYP11A1. The findings suggest that administration of ODM-208 is feasible with concomitant corticosteroid replacement therapy.

Prepubertal Use of Long-Term GnRH Agonists in Dogs: Current Knowledge and Recommendations.

Simple SummaryDelay of puberty is sometimes desired by pet owners and can prevent early occurrence of estrus and unwanted pregnancies. Long-term delay of puberty is possible with GnRH agonists such as deslorelin that can be applied as subcutaneous implants. Many studies have been performed to investigate the best age for implantation, and whether undesired side-effects on body development, height at whither, and behavior may occur. At present, most important appears the age at implantation in that one 4.7 mg deslorelin implant should be inserted s.c. between the 3rd and 4th month of life to prevent a flare-up or induction of estrus. Body development as well as fertility after occurrence of first heat after the end of efficacy were normal. However, long-term effects on joint health, tumor development, immune system, and behavior deserve further investigation.The search for an alternative approach of estrus control (induction or suppression) in dogs is an important issue and the use of slow GnRH agonist-releasing implants has been the subject of frequent research in recent years. Studies to date demonstrate that the short- and long-term effects of deslorelin implants applicated at different time points of the prepubertal period are similar to those of adult dogs; however, there are important differences. The age of the prepubertal bitch and the dosage appear to be the main determinants of the response to deslorelin, as well as the individual metabolism of the bitch. Recent studies reported that the deslorelin-mediated long-term delay of puberty does not have negative carry-over effects on subsequent ovarian functionality, serum steroid hormone concentrations, uterine health, and fertility; however, more molecular studies are needed to determine the effects of application time of GnRH agonists on hormone concentrations and peripheral receptor expression. Furthermore, the long-term effects of delay of puberty with deslorelin on joint health, tumor development, the immune system, and social behavior deserve further investigations.

Hormonal patterns in men with prediabetes and diabetes in NHANES III: possible links with prostate cancer.

Pathways involving sex hormones and insulin-like growth factors (IGFs) have been proposed to explain, in part, the lower risk of prostate cancer among men with diabetes. To gain insights into potential biological mechanisms we explored differences in serum concentrations of sex hormones and IGFs across the trajectory from normoglycemia to prediabetes to poorly controlled diabetes. Using cross-sectional data from the National Health and Nutrition Examination Survey III we examined differences in levels of circulating sex hormones, sex hormone-binding globulin (SHBG), IGF-1, and IFG-binding protein 3 (IGFBP-3), according to diabetes status: no diabetes [n = 648], prediabetes [n = 578], undiagnosed diabetes [n = 106], well-controlled diabetes [n = 42], and poorly controlled diabetes [n = 56]. Adjusted geometric mean concentrations were derived using multivariable linear regression, adjusted for age, race, and other lifestyle factors. Total testosterone concentrations were lower among prediabetics (4.89ng/mL, 95% confidence interval (CI) 4.95-5.21) than men without prediabetes/diabetes (5.29ng/mL, 95% CI 5.06-5.53) but did not reduce further across diabetes groups. Concentrations of estradiol, estimated free testosterone, SHGB, IGF-1, and IGFBP-3 did not differ. While the ratio of IGF-1 to IGFBP-3 was lower among men with prediabetics and undiagnosed diabetes than men without prediabetes/diabetes, there was no trend across groups. A positive trend for the ratio of estradiol-to-testosterone levels was observed across groups (p trend = 0.045). Our findings do not provide clear support for either an androgen driven or IGF-driven pathway for the inverse association between diabetes and prostate cancer risk.

Comprehensive Sex Steroid Profiling in Multiple Tissues Reveals Novel Insights in Sex Steroid Distribution in Male Mice.

A comprehensive atlas of sex steroid distribution in multiple tissues is currently lacking, and how circulating and tissue sex steroid levels correlate remains unknown. Here, we adapted and validated a gas chromatography tandem mass spectrometry method for simultaneous measurement of testosterone (T), dihydrotestosterone (DHT), androstenedione, progesterone (Prog), estradiol, and estrone in mouse tissues. We then mapped the sex steroid pattern in 10 different endocrine, reproductive, and major body compartment tissues and serum of gonadal intact and orchiectomized (ORX) male mice. In gonadal intact males, high levels of DHT were observed in reproductive tissues, but also in white adipose tissue (WAT). A major part of the total body reservoir of androgens (T and DHT) and Prog was found in WAT. Serum levels of androgens and Prog were strongly correlated with corresponding levels in the brain while only modestly correlated with corresponding levels in WAT. After orchiectomy, the levels of the active androgens T and DHT decreased markedly while Prog levels in male reproductive tissues increased slightly. In ORX mice, Prog was by far the most abundant sex steroid, and, again, WAT constituted the major reservoir of Prog in the body. In conclusion, we present a comprehensive atlas of tissue and serum concentrations of sex hormones in male mice, revealing novel insights in sex steroid distribution. Brain sex steroid levels are well reflected by serum levels and WAT constitutes a large reservoir of sex steroids in male mice. In addition, Prog is the most abundant sex hormone in ORX mice.

Fluctuations in serum steroid hormone concentrations and body mass during growth and sexual maturation in captive northern fur seals (Callorhinus ursinus).

Northern fur seals (Callorhinus ursinus) have a distinct life history pattern comprising annual terrestrial breeding and oceanic migration, and the physiological changes associated with these patterns are of particular interest for understanding their environmental adaptations. However, owing to their oceanic distribution, limited information is available on the reproductive physiology of wild individuals during the immature stage and the winter migration period. This study aimed to determine the relationships among the seasonal hormone profiles, body growth, age, and pregnancy using monthly serum samples collected over 3–5 years from two male and two female captive individuals during pubescence and sexual maturation. Small increases in the serum testosterone signaled puberty in males aged 3 and 4 years. Thereafter, males showed considerable increases in testosterone during breeding seasons, indicating sexual maturity. Immature female serum progesterone was maintained at low levels, but after pubescence, females showed an increase in serum progesterone in August, the month next to the peak of delivery, followed by a decrease. In non-pregnant females, progesterone did not increase significantly until the next breeding season, but in pregnant females, they increased again from February to March and then gradually decreased. Immature males increased body mass constantly and reached puberty when their body mass exceeded 20 kg, and they showed seasonal weight fluctuations after puberty. These results provide fundamental information for determining sexual maturity and pregnancy in this species based on sex steroid hormones and body mass measurements.

Shifts in the Skin Bacterial and Fungal Communities of Healthy Children Transitioning through Puberty

Previous cross-sectional studies have shown that skin microbiomes in adults are distinct from those in children. However, the human skin microbiome in individuals as they sexually mature has not been studied as extensively. We performed a prospective, longitudinal study to investigate the puberty-associated shifts in skin microbiota. A total of 12 healthy children were evaluated every 6-18 months for up to 6 years. Using 16S ribosomal RNA (V1-V3) and internal transcribed spacer 1 amplicon sequencing analyzed with Divisive Amplicon Denoising Algorithm 2, we characterized the bacterial and fungal communities of five different skin and nares sites. We identified significant alterations in the composition of skin microbial communities, transitioning toward a more adult microbiome, during puberty. The microbial shifts were associated with Tanner stages (classification method for the degree of sexual maturation) and showed noticeable sex-specific differences. Over time, female children demonstrated a predominance of Cutibacterium with decreasing diversity. Among fungi, Malassezia predominated at most skin sites in more sexually mature subjects, which was more pronounced in female children. The higher relative abundances of these lipophilic taxa-C.acnes and M.restricta-were strongly associated with serum sex hormone concentrations with known influence on sebaceous gland activity. Taken together, our results support the relationship between sexual maturation, skin physiology, and the skin microbiome.