Investigating the Potential of Perovskite Nanocrystal-Doped Liquid Scintillator: A Feasibility Study.

Liquid scintillators are extensively employed as targets in neutrino experiments and in medical radiography. Perovskite nanocrystals are recognized for their tunable emission spectra and high photoluminescence quantum yields. In this study, we investigated the feasibility of using perovskites as an alternative to fluor, a substance that shifts the wavelengths. The liquid scintillator candidates were synthesized by doping perovskite nanocrystals with emission wavelengths of 450, 480, and 510 nm into fluor PPO with varying nanocrystal concentrations in a toluene solvent. The several properties of the perovskite nanocrystal-doped liquid scintillator were measured and compared with those of a secondary wavelength shifter, bis-MSB. The emission spectra of the perovskite nanocrystal-doped liquid scintillator exhibited a distinct monochromatic wavelength, indicating energy transfer from PPO to the perovskite nanocrystals. Using a 60Co radioactive source setup with two photomultiplier tubes (PMTs), the light yields, pulse shape, and wavelength shifts of the scintillation events were measured. The light yields were evaluated based on the observed Compton edges from γ-rays, and compared across the synthesized samples. A decrease (or increase) in area-normalized PMT pulse height was observed at higher perovskite nanocrystal (or PPO) concentrations. The results demonstrated the sufficient potential of perovskite nanocrystals as an alternative to traditional wavelength shifters in a liquid scintillator.

EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) and Other Patient-Reported Outcomes in the Assessment of Glandular Dysfunction in Primary Sjögren's Syndrome.

The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), and other patient-reported outcomes (PROs), such as the visual analog scale (VAS) for symptoms and EULAR sicca score (ESS), are used to assess the disease activity of primary Sjögren's syndrome (pSS). Recently, Clinical ESSDAI (ClinESSDAI) and Clinical Trials ESSDAI (ClinTrialsESSDAI) were developed for objective clinical disease activity indexes. However, the relationship of ClinESSDAI and ClinTrialsESSDAI with PROs as well as that between ESSPRI and other PROs and the objective parameters of glandular function in pSS have not been established. Herein, we investigated the correlation of ESSPRI and other PROs with the objective parameters of glandular function and the relationship of PROs with ClinESSDAI and ClinTrialsESSDAI in 66 patients with pSS. Correlations were calculated with Spearman's correlation coefficient. ClinTrialsESSDAI was correlated with ESSPRI, dryness (ESSPRI-Dryness), fatigue, and pain domains of ESSPRI, VAS for oral dryness (oral-VAS), and patient's global assessment. Although ESSPRI did not correlate with the objective parameters of glandular function, ESSPRI-Dryness, ESS, and oral- and ocular-VAS did. These results suggest that ESSPRI-Dryness, ESS, and VAS for symptoms, but not ESSPRI, reflect the glandular dysfunction and that ClinTrialsESSDAI correlates with PROs for dryness in pSS.

Tumor-like Presentation of Cerebral Vasculitis in a Patient With Systemic Lupus Erythematosus: A Biopsy-confirmed Case.

Central nervous system (CNS) manifestations of systemic lupus erythematosus (SLE) are diverse and often difficult to distinguish from SLE-unrelated events. CNS vasculitis is a rare manifestation, which is seen in less than 10% of post-mortem studies, and lesions with multifocal cerebral cortical microinfarcts associated with small-vessel vasculitis are the predominant feature. However, CNS vasculitis presenting as a tumor-like mass lesion in SLE has rarely been reported. Herein, we report a case of cerebral vasculitis mimicking a brain tumor in a 39-year-old female with SLE. A biopsy of the brain mass revealed fibrinoid necrosis and leukocytoclastic vasculitis. The neurological deficits and systemic symptoms improved after treatment with corticosteroids and immunosuppressive agents. To the best of our knowledge, there are no reports of biopsy-proven cerebral vasculitis presenting as a brain mass in patients with SLE in Korea.

Longitudinal relationship between depression and antisocial behaviors in Korean adolescents.

Background: It is well known that depression and delinquency in adolescents are highly correlated, but longitudinal studies on the causal relationship between them are not active in East Asia compared to in Western culture. In addition, even the results of research on causal models and sex differences are inconsistent. Objectives: This study examines the longitudinal reciprocal effects between depression and delinquent behavior in Korean adolescents based on sex differences. Methods: We conducted multiple-group analysis by using an autoregressive cross-lagged model (ACLM). Longitudinal data from 2,075 individuals (2011-2013) were used for analysis. The longitudinal data are from the Korean Children and Youth Panel Survey (KCYPS), and data were used beginning with students at 14 years old (in the second grade of middle school) and tracked them until they were 16 (in the first grade of high school). Results: Boys' delinquent behaviors at 15 years (the third grade of middle school) affected their depression at 16 years (the first grade of high school). In contrast, girls' depression at 15 years (the third grade of middle school) influenced their delinquent behaviors at 16 years (the first grade of high school). Discussion: The findings support the failure model (FM) among adolescent boys and the acting-out model (ACM) among girls. The results imply that strategies to effectively prevent and treat delinquency and depression in adolescents must consider sex effects.

Testosterone Restores Body Composition, Bone Mass, and Bone Strength Following Early Puberty Suppression in a Mouse Model Mimicking the Clinical Strategy in Trans Boys.

Transgender youth increasingly present at pediatric gender services. Some of them receive long-term puberty suppression with gonadotropin-releasing hormone analogues (GnRHa) before starting gender-affirming hormones (GAH). The impact of GnRHa use started in early puberty on bone composition and bone mass accrual is unexplored. It is furthermore unclear whether subsequent GAH fully restore GnRHa effects and whether the timing of GAH introduction matters. To answer these questions, we developed a mouse model mimicking the clinical strategy applied in trans boys. Prepubertal 4-week-old female mice were treated with GnRHa alone or with GnRHa supplemented with testosterone (T) from 6 weeks (early puberty) or 8 weeks (late puberty) onward. Outcomes were analyzed at 16 weeks and compared with untreated mice of both sexes. GnRHa markedly increased total body fat mass, decreased lean body mass, and had a modest negative impact on grip strength. Both early and late T administration shaped body composition to adult male levels, whereas grip strength was restored to female values. GnRHa-treated animals showed lower trabecular bone volume and reduced cortical bone mass and strength. These changes were reversed by T to female levels (cortical bone mass and strength) irrespective of the time of administration or even fully up to adult male control values (trabecular parameters) in case of earlier T start. The lower bone mass in GnRHa-treated mice was associated with increased bone marrow adiposity, also reversed by T. In conclusion, prolonged GnRHa use started in prepubertal female mice modifies body composition toward more fat and less lean mass and impairs bone mass acquisition and strength. Subsequent T administration counteracts GnRHa impact on these parameters, shaping body composition and trabecular parameters to male values while restoring cortical bone architecture and strength up to female but not male control levels. These findings could help guide clinical strategies in transgender care. © 2023 American Society for Bone and Mineral Research (ASBMR).

Estimating Fluor Emission Spectra Using Digital Image Analysis Compared to Spectrophotometer Measurements.

This paper describes a practical method for obtaining the spectra of lights emitted by a fluor in a liquid scintillator (LS) using a digital camera. The emission wavelength results obtained using a digital image were compared with those obtained using a fluorescence spectrophotometer. For general users, conventional spectrophotometers are expensive and difficult to access. Moreover, their experimental measurement setup and processes are highly complicated, and they require considerable care in handling. To overcome these limitations, a feasibility study was performed to obtain the emission spectrum through image analysis. Specifically, the emission spectrum of a fluor dissolved in a liquid scintillator was obtained using digital image analysis. An image processing method was employed to convert the light irradiated during camera exposure into wavelengths. Hue (H) and wavelength (W) are closely related. Thus, we obtained an H-W response curve in the 400~450 nm wavelength region, using a light-emitting diode. Another relevant advantage of the method described in this study is its non-invasiveness in sealed LS samples. Our results showed that this method has the potential to accurately investigate the emission wavelengths of fluor within acceptable uncertainties. We envision the use of this method to perform experiments in chemistry and physics laboratories in the future.

Feasibility Study on the Discrimination of Fluor Concentration in the Liquid Scintillator Using PMT Waveform and Short-Pass Filter.

Neutrinos are difficult to detect because they weakly interact with matter, making their properties least known. The response of the neutrino detector depends on the optical properties of the liquid scintillator (LS). Monitoring any characteristic changes in the LS helps to understand the temporal variation of detector response. In this study, a detector filled with LS was used to study the characteristics of the neutrinos detector. We investigated a method to distinguish the concentrations of PPO and bis-MSB, which are fluors added to LS, through a photomultiplier tube (PMT) acting as an optical sensor. Conventionally, it is very challenging to discriminate the flour concentration dissolved in LS. We employed the information of pulse shape and PMT coupled with the short-pass filter. To date, no literature report on a measurement using such an experimental setup has been published. As the concentration of PPO was increased, changes in the pulse shape were observed. In addition, as the concentration of bis-MSB was increased, a decrease in the light yield was observed in the PMT equipped with the short-pass filter. This result suggests the feasibility of real-time monitoring of LS properties, which are correlated with the fluor concentration, using a PMT without extracting the LS samples from the detector during the data acquisition process.

New-onset retroperitoneal fibrosis following COVID-19 mRNA vaccination: Coincidental or vaccine-induced phenomenon?

The Pfizer-BioNTech mRNA vaccine is a US Food and Drug Administration-approved coronavirus disease 2019 (COVID-19) vaccine. Although it is reported to be safe and effective, immune dysregulation leading to autoimmunity has become an area of concern. Retroperitoneal fibrosis (RPF) is an immune-mediated fibroinflammatory disease characterized by the deposition of fibrous tissues, primarily around the abdominal aorta and iliac arteries. Herein, we report a case of RPF following Pfizer BioNTech COVID-19 mRNA vaccination. To the best of our knowledge, there have been no published reports on RPF after COVID-19 mRNA vaccination. A 58-year-old woman with no history of autoimmune diseases presented with acute onset of epigastric pain 5 weeks after the second dose of the Pfizer-BioNTech vaccine. She had been diagnosed with stage I breast cancer 9 years ago and was in complete remission on admission. Abdominal computed tomography showed preaortic soft-tissue infiltration around the origin of the superior mesenteric artery but no evidence of breast cancer recurrence. Considering the temporal relationship between current symptoms and vaccination and the absence of other possible causes, she was diagnosed with RPF secondary to Pfizer-BioNTech vaccine-induced autoimmunity. This case may raise awareness of the possibility of RPF development following COVID-19 mRNA vaccination.

Investigation of the Hue-Wavelength Response of a CMOS RGB-Based Image Sensor.

In this study, a non-linear hue-wavelength (H-W) curve was investigated from 400 to 650 nm. To date, no study has reported on H-W relationship measurements, especially down to the 400 nm region. A digital camera mounted with complementary metal oxide semiconductor (CMOS) image sensors was used. The obtained digital images of the sample were based on an RGB-based imaging analysis rather than multispectral imaging or hyperspectral imaging. In this study, we focused on the raw image to reconstruct the H-W curve. In addition, several factors affecting the digital image, such as exposure time or international organization for standardization (ISO), were investigated. In addition, cross check of the H-W response using laser was performed. We expect that our method will be useful as an auxiliary method in the future for obtaining the fluor emission wavelength information.

Dipeptidyl peptidase-4 inhibitory potentials of Glycyrrhiza uralensis and its bioactive compounds licochalcone A and licochalcone B: An in silico and in vitro study.

Type 2 diabetes mellitus (T2DM) is a growing global public health issue, and dipeptidyl peptidase-4 (DPP-4) is a potential therapeutic target in T2DM. Several synthetic anti-DPP-4 medications can be used to treat T2DM. However, because of adverse effects, there is an unmet demand for the development of safe and effective medications. Natural medicines are receiving greater interest due to the inherent safety of natural compounds. Glycyrrhiza uralensis (licorice) is widely consumed and used as medicine. In this study, we investigated the abilities of a crude water extract (CWE) of G. uralensis and two of its constituents (licochalcone A (LicA) and licochalcone B (LicB)) to inhibit the enzymatic activity of DPP-4 in silico and in vitro. In silico studies showed that LicA and LicB bind tightly to the catalytic site of DPP-4 and have 11 amino acid residue interactions in common with the control inhibitor sitagliptin. Protein-protein interactions studies of LicA-DPP4 and LicB-DPP4 complexes with GLP1 and GIP reduced the DPP-4 to GLP1 and GIP interactions, indicated that these constituents might reduce the degradations of GLP1 and GIP. In addition, molecular dynamics simulations revealed that LicA and LicB stably bound to DPP-4 enzyme. Furthermore, DPP-4 enzyme assay showed the CWE of G. uralensis, LicA, and LicB concentration-dependently inhibited DPP-4; LicA and LicB had an estimated IC50 values of 347.93 and 797.84 µM, respectively. LicA and LicB inhibited DPP-4 at high concentrations, suggesting that these compounds could be used as functional food ingredients to manage T2DM.

The Spectrum of Light Emitted by LED Using a CMOS Sensor-Based Digital Camera and Its Application.

We introduced a digital photo image analysis in color space to estimate the spectrum of fluor components dissolved in a liquid scintillator sample through the hue and wavelength relationship. Complementary metal oxide semiconductor (CMOS) image sensors with Bayer color filter array (CFA) technology in the digital camera were used to reconstruct and decode color images. Hue and wavelength are closely related. To date, no literature has reported the hue and wavelength relationship measurements, especially for blue or close to the UV region. The non-linear hue and wavelength relationship in the blue region was investigated using a light emitting diode source. We focused on this wavelength region, because the maximum quantum efficiency of the bi-alkali photomultiplier tube (PMT) is around 430 nm. It is necessary to have a good understanding of this wavelength region in PMT-based experiments. The CMOS Bayer CFA approach was sufficient to estimate the fluor emission spectrum in the liquid scintillator sample without using an expensive spectrophotometer.

Inactivation of AR or ERα in Extrahypothalamic Neurons Does not Affect Osteogenic Response to Loading in Male Mice.

Failure of bone mass maintenance in spite of functional loading is an important contributor to osteoporosis and related fractures. While the link between sex steroids and the osteogenic response to loading is well established, the underlying mechanisms are unknown, hampering clinical relevance. Androgens inhibit mechanoresponsiveness in male mice, but the cell type mediating this effect remains unidentified. To evaluate the role of neuronal sex steroid receptor signaling in the male bone's adaptive capacity, we subjected adult male mice with an extrahypothalamic neuron-specific knockout of the androgen receptor (N-ARKO) or the estrogen receptor alpha (N-ERαKO) to in vivo mechanical stimulation of the tibia. Loading increased cortical thickness in the control animals mainly through periosteal expansion, as total cross-sectional tissue area and cortical bone area but not medullary area were higher in the loaded than the unloaded tibia. Trabecular bone volume fraction also increased upon loading in the control group, mostly due to trabecular thickening. N-ARKO and N-ERαKO males displayed a loading response at both the cortical and trabecular bone compartments that was not different from their control littermates. In conclusion, we show that the presence of androgen receptor or estrogen receptor alpha in extrahypothalamic neurons is dispensable for the osteogenic response to mechanical loading in male mice.

Reappraisal of bone scintigraphy as a new tool for the evaluation of disease activity in patients with rheumatoid arthritis.

We aimed to compare the reliability of bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-derived parameters in the detection of active arthritis in 28-joint areas and evaluate the reliability of joint counts between BS and clinical assessment in patients with rheumatoid arthritis (RA). We enrolled 106 patients (67 in the development group and 39 in the validation groups) with active RA who underwent BS, 18F-FDG PET/computed tomography (CT), and clinical evaluation of disease activity. We compared the results of BS-derived joint assessment with those of PET-derived and clinical joint assessments. Subsequently we developed a disease activity score (DAS) using BS-positive joints and validated it in an independent group. The number of BS-positive joints in 28-joint areas significantly correlated with the swollen /tender joint counts (SJC/TJC) and PET-derived joint counts. A BS uptake score of 2 (strong positive) was significantly more sensitive compared with a BS uptake score of 1 (weak positive) in detecting a PET-positive joint among the 28-joints. After conducting multivariate analyses including erythrocyte sediment rate (ESR) and patient global assessment (PGA) in addition to BS-derived parameters, BS/DAS was obtained as follows: 0.056 × number of BS-positive joints in 28 joints + 0.012 × ESR + 0.030 × PGA. A significant correlation between BS/DAS and DAS28-ESR was confirmed in the validation group. Strong positive uptake of BS is sensitive and reproducible for the detection of active joints, and can complement the clinical assessment of disease activity in RA.

Radial BMD and serum CTX-I can predict the progression of carotid plaque in rheumatoid arthritis: a 3-year prospective cohort study.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are almost twice as likely to develop cardiovascular disease (CVD) as those without. However, traditional CVD risks have been shown to underperform in RA patients; thus, we aimed to identify new surrogate risk factors to better reflect their atherosclerotic burden. METHODS: A total of 380 RA patients with carotid atherosclerosis data were analyzed in this prospective cohort study. The primary outcome was carotid plaque progression over the 3-year follow-up period. Risk parameters assessed for the progression of carotid plaque were categorized as demographics, traditional CVD risks, RA-related risks, and bone parameters. RESULTS: The progression of carotid plaque was associated with the level of rheumatoid factor (p = 0.025), serum C-terminal telopeptide of type-I collagen (CTX-I) (p = 0.014), and femur and distal radius bone mass density (BMD) (p = 0.007 and 0.004, respectively), as well as traditional CVD risk factors. In multivariable analyses, the bone parameters of serum CTX-I and distal radius BMD proved to be independent predictors of the progression of carotid plaque along with hyperlipidemia, smoking, and baseline carotid plaque (all, p < 0.05). Adding both serum CTX-I and distal radius BMD increased the carotid plaque progression prediction model's percentage of explained variance from 24 to 30%. CONCLUSION: High serum CTX-I and lower radius BMD, reflecting high bone turnover, were independent risk factors for the progression of carotid plaque in RA patients, implicating the direct or indirect role of bone metabolism on the atherosclerotic burden.

Combination of Bifidobacterium longum and Galacto-Oligosaccharide Protects the Skin from Photoaging.

Overexposure to ultraviolet B (UVB) irradiation induces photoaging that is characterized by the formation of wrinkles and loss of skin elasticity. To understand the mechanism of action of probiotics and prebiotics in skin protection against photoaging, we investigated the effects of dietary supplementation with the probiotic, Bifidobacterium longum, and prebiotic, galacto-oligosaccharide, on UVB-induced photoaging in hairless mice. We measured short chain fatty acid (SCFA) levels, antioxidant enzyme activity, and inflammatory signaling protein levels to elucidate the possible mechanisms underlying the effects of the dietary supplements B. longum and galacto-oligosaccharide. We observed that dietary supplementation with B. longum and galacto-oligosaccharide, individually and in combination, exerted protective effects against UVB-induced photoaging, showing anti-inflammatory and antioxidative effects. In particular, supplementation with the combination of B. longum and galacto-oligosaccharide showed stronger protective effects than supplementation with the probiotic or prebiotic alone. In addition, the serum levels of SCFAs and acetate were increased following dietary supplementation with B. longum and galacto-oligosaccharide, especially in combination. Therefore, we suggest that the combination of B. longum and galacto-oligosaccharide may potentially be used as a functional food to protect UVB-induced photoaging.

Testosterone Reduces Body Fat in Male Mice by Stimulation of Physical Activity Via Extrahypothalamic ERα Signaling.

Testosterone (T) reduces male fat mass, but the underlying mechanisms remain elusive, limiting its clinical relevance in hypogonadism-associated obesity. Here, we subjected chemically castrated high-fat diet-induced adult obese male mice to supplementation with T or the nonaromatizable androgen dihydrotestosterone (DHT) for 20 weeks. Both hormones increased lean mass, thereby indirectly increasing oxygen consumption and energy expenditure. In addition, T but not DHT decreased fat mass and increased ambulatory activity, indicating a role for aromatization into estrogens. Investigation of the pattern of aromatase expression in various murine tissues revealed the absence of Cyp19a1 expression in adipose tissue while high levels were observed in brain and gonads. In obese hypogonadal male mice with extrahypothalamic neuronal estrogen receptor alpha deletion (N-ERαKO), T still increased lean mass but was unable to decrease fat mass. The stimulatory effect of T on ambulatory activity was also abolished in N-ERαKO males. In conclusion, our work demonstrates that the fat-burning action of T is dependent on aromatization into estrogens and is at least partially mediated by the stimulation of physical activity via extrahypothalamic ERα signaling. In contrast, the increase in lean mass upon T supplementation is mediated through the androgen receptor and indirectly leads to an increase in energy expenditure, which might also contribute to the fat-burning effects of T.

Novel model to study the physiological effects of temporary or prolonged sex steroid deficiency in male mice.

Sex steroids are critical for skeletal development and maturation during puberty as well as for skeletal maintenance during adult life. However, the exact time during puberty when sex steroids have the highest impact as well as the ability of bone to recover from transient sex steroid deficiency is unclear. Surgical castration is a common technique to study sex steroid effects in rodents, but it is irreversible, invasive, and associated with metabolic and behavioral alterations. Here, we used a low dose (LD) or a high dose (HD) of gonadotropin-releasing hormone antagonist to either temporarily or persistently suppress sex steroid action in male mice, respectively. The LD group, a model for delayed puberty, did not show changes in linear growth or body composition, but displayed reduced trabecular bone volume during puberty, which fully caught up at adult age. In contrast, the HD group, representing complete pubertal suppression, showed a phenotype reminiscent of that observed in surgically castrated rodents. Indeed, HD animals exhibited severely impaired cortical and trabecular bone acquisition, decreased body weight and lean mass, and increased fat mass. In conclusion, we developed a rodent model of chemical castration that can be used as an alternative to surgical castration. Moreover, the transient nature of the intervention enables to study the effects of delayed puberty and reversibility of sex steroid deficiency.NEW & NOTEWORTHY We developed a rodent model of chemical castration, which can be used as an alternative to surgical castration. Moreover, the transient nature of the intervention enables to study the effects of delayed puberty and reversibility of sex steroid deficiency.

Androgen action on renal calcium and phosphate handling: Effects of bisphosphonate treatment and low calcium diet.

Renal calcium and phosphate handling is an important contributor to mineral homeostasis and bone health and the androgen receptor (AR) is highly expressed in the kidney. We investigated the short term effects of androgen deprivation on renal calcium and phosphate reabsorption, independent of their effects on bone. Two weeks following orchidectomy (ORX) of adult mice, bone loss occurred along with hypercalciuria, which was similarly prevented by testosterone and dihydrotestosterone supplementation. Treatment with bisphosphonates prior to ORX also inhibited hypercalciuria, indicating that the calcium flux originated from the bone. Renal calcium and phosphate transporter expression was increased post-ORX, independent of bisphosphonates. Furthermore, androgen deprivation appeared to stimulate local synthesis of 1,25(OH)2D3. When bisphosphonate-treated mice were fed a low calcium diet, bone resorption was no longer blocked and secondary hyperparathyroidism developed, which was more pronounced in ORX mice than sham-operated mice. In conclusion, this study shows that androgen deprivation increased renal calcium and phosphate transporter expression, independent of bone, and underlines the importance of adequate intestinal calcium supply in circumstances of androgen deprivation and bisphosphonate treatment.

Early effects of androgen deprivation on bone and mineral homeostasis in adult men: a prospective cohort study.

OBJECTIVE: Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. DESIGN: Prospective cohort study. METHODS: Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied. RESULTS: Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7-35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. CONCLUSIONS: In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.

Estrogen receptor alpha signaling in extrahypothalamic neurons during late puberty decreases bone size and strength in female but not in male mice.

Sexually dimorphic bone structure emerges largely during puberty. Sex steroids are critical for peak bone mass acquisition in both genders. In particular, the biphasic effects of estrogens mediate the skeletal sexual dimorphism. However, so far the stimulatory vs inhibitory actions of estrogens on bone mass are not fully explained by direct effects on bone cells. Recently, it has become evident that there is possible neuroendocrine action of estrogen receptor alpha (ERα) on the skeleton. Based on these considerations, we hypothesized that neuronal ERα-signaling may contribute to the skeletal growth during puberty. Here, we generated mice with tamoxifen-inducible Thy1-Cre mediated ERα inactivation during late puberty specifically in extrahypothalamic neurons (N-ERαKO). Inactivation of neuronal ERα did not alter the body weight in males, whereas N-ERαKO females exhibited a higher body weight and increased body and bone length compared to their control littermates at 16 weeks of age. Ex vivo microCT analysis showed increased radial bone expansion of the midshaft femur in female N-ERαKO along with higher serum levels of insulin-like growth factor (IGF)-1 as well as IGF-binding protein (IGFBP)-3. Furthermore, the 3-point bending test revealed increased bone strength in female N-ERαKO. In contrast, inactivation of neuronal ERα had no major effect on bone growth in males. In conclusion, we demonstrate that central ERα-signaling limits longitudinal bone growth and radial bone expansion specifically in females potentially by interacting with the GH/IGF-1 axis.