Publisher: Endocrine Society, The   (Total: 3 journals)   [Sort by number of followers]

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Endocrine Reviews     Full-text available via subscription   (Followers: 44, SJR: 6.402, CiteScore: 13)
Endocrinology     Full-text available via subscription   (Followers: 50, SJR: 1.878, CiteScore: 4)
J. of Clinical Endocrinology & Metabolism     Full-text available via subscription   (Followers: 140, SJR: 2.941, CiteScore: 5)
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Endocrinology
Journal Prestige (SJR): 1.878
Citation Impact (citeScore): 4
Number of Followers: 50  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 0013-7227 - ISSN (Online) 1945-7170
Published by Endocrine Society, The Homepage  [3 journals]
  • Correction to: Hormonally Regulated Myogenic miR-486 Influences
           Sex-specific Differences in Cancer-induced Skeletal Muscle Defects

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      Abstract: In the above-named article by Wang R, Bhat-Nakshatri P, Zhong X, Zimmers T, and Nakshatri H (Endocrinology. 2021, 162(10); doi: 10.1210/endocr/bqab142), an error appeared in Figure 7:
      PubDate: Mon, 08 Aug 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqab142), an error appeared in figure 7:
      Issue No: Vol. 163, No. 9 (2022)
       
  • Multisensory Stimulation Improves Cognition and Behavior in Adult Male
           Rats Born to LT4-treated Thyroidectomized Dams

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      Abstract: AbstractGestational hypothyroidism can impair development, cognition, and mood. Here, we tested whether multisensory stimulation (MS) improves the phenotype of rats born to surgically thyroidectomized (Tx) dams suboptimally treated with LT4. 8-week-old female Tx Wistar rats were kept on daily LT4 (0.7 µg/100 g body weight) dosed by gavage (serum TSH and T4 levels indicated moderate hypothyroidism) and 3 weeks later placed for breeding. MS of the litter started at age 60 days and lasted for 8 weeks. It consisted of twice per week of physical, cognitive, sensorial, and food stimuli. The offspring were assessed before and after MS for standardized tests of locomotor activity, cognition, and mood. Gestational hypothyroidism resulted in reduced litter size and increased offspring mortality. The pups exhibited delayed physical development, impairment of short- and long-term memory, and anxiety- and depressive-like behaviors. Nonetheless, ambulatory activity, social memory, and social preference were not affected by gestational hypothyroidism. MS restored short-term memory and anxiety while improving depressive like-behaviors. MS did not improve long-term memory. MS also did not modify the performance of control litter born to intact dams. We conclude that cognition and mood impairments caused by moderate gestational hypothyroidism were reversed or minimized in rats through MS. Further studies should define the molecular mechanisms involved.
      PubDate: Mon, 01 Aug 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac105
      Issue No: Vol. 163, No. 9 (2022)
       
  • N/C Interactions Are Dispensable for Normal In Vivo Functioning of the
           Androgen Receptor in Male Mice

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      Abstract: AbstractThe androgen receptor (AR) plays a central role in the development and maintenance of the male phenotype. The binding of androgens to the receptor induces interactions between the carboxyterminal ligand-binding domain and the highly conserved 23FQNLF27 motif in the aminoterminal domain. The role of these so-called N/C interactions in AR functioning is debated. In vitro assays show that mutating the AR in the 23FQNLF27 motif (called ARNoC) attenuates the AR transactivation of reporter genes, has no effect on ligand binding, but does affect protein-protein interactions with several AR coregulators. To test the in vivo relevance of the N/C interaction, we analyzed the consequences of the genomic introduction of the ARNoC mutation in mice. Surprisingly, the ARNoC/Y mice show a normal male development, with unaffected male anogenital distance and normal accessory sex glands, male circulating androgen levels, body composition, and fertility. The responsiveness of androgen target genes in kidney, prostate, and testes was also unaffected. We thus conclude that the N/C interactions in the AR are not essential for the development of a male phenotype under normal physiological conditions.
      PubDate: Sun, 31 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac104
      Issue No: Vol. 163, No. 9 (2022)
       
  • Correction to: Leprdb/+ Dams Protect Wild-type Male Offspring Bone
           Strength from the Detrimental Effects of a High-Fat Diet

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      Abstract: In the above-named article by Oestreich AK, Onuzuruike A, Yao X, Talton O, Wang Y, Pfeiffer FM, Schulz LC, and Phillips CL (Endocrinology 2020, 161(8); doi: 10.1210/endocr/bqaa087), there was an error in the author list.
      PubDate: Sat, 30 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac114
      Issue No: Vol. 163, No. 9 (2022)
       
  • Leptin Promotes Primordial Follicle Activation by Regulating Ovarian
           Insulin-like Growth Factor System in Chicken

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      Abstract: AbstractLeptin and insulin-like growth factor 1 (IGF-1) regulate follicle development and reproduction in vertebrates. This study investigated the role played by leptin and IGF-1 in primordial follicle activation in the ovary of 7-day-old chicks. Different doses of leptin were intraperitoneally administrated to female layer chicks, and further analyses were performed. While leptin administration did not affect hepatic leptin receptor (LEPR), growth hormone receptor (GHR), or IGF-1, the lower dose of leptin significantly increased the messenger RNA (mRNA) expression of IGF-1, IGF-1 receptor, and IGF-binding protein (IGFBP)-2 and attenuated anti-Müllerian hormone (AMH) gene expression in the ovary. Furthermore, the ovaries of the same age chicks were challenged with leptin and/or IGF-1 in vitro. Leptin at a lower dose increased the mRNA expression of IGF-1, LEPR, and leptin; 100 ng/mL leptin and 10 ng/mL IGF-1 alone or combined with leptin reduced IGFBP-2 mRNA expression. AMH gene expression was also reduced by all doses except 10 ng/mL leptin. Histological studies showed that a lower dose of leptin injection induced the primordial follicle growth in the ovary in vivo, and the number of primordial follicles was higher in all leptin treatments over control in vitro. Moreover, the luciferase assay revealed that leptin enhanced IGF-1 promoter activity in LEPR-expressing CHO-K1 cells. Collectively, these results indicate that leptin directly affects the IGF-1/IGFBP system and promotes primordial follicular growth in the ovary of early posthatch chicks. In addition, the follicular development by leptin-induced IGF-1 is, at least in part, caused by the suppression of AMH in the ovary.
      PubDate: Wed, 27 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac112
      Issue No: Vol. 163, No. 9 (2022)
       
  • CUX2/KDM5B/SOX17 Axis Affects the Occurrence and Development of Breast
           Cancer

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      Abstract: AbstractObjectiveAbnormal expression of CUT-like homeobox 2 gene (CUX2) has been highlighted as potential clinical biomarkers in human cancers. Notably, the function of CUX2 has been less elucidated in breast cancer (BC). We focused on the role of the CUX2 in tumorigenesis and progression of BC with the involvement of the lysine demethylase 5B (KDM5B)/sex determining region Y-box 17 (SOX17) axis.MethodsCUX2, KDM5B, and SOX17 expression levels in BC tissues and cells were tested by reverse transcription quantitative PCR and Western blotting. Later, the effects of CUX2, KDM5B, and SOX17 on the malignant behaviors of MDA-MB-231 and MCF-7 cells were analyzed by CCK-8, colony formation, and Transwell assays in vitro. The interactions of CUX2, KDM5B, and SOX17 were validated by online website prediction, ChIP assay, and dual luciferase reporter gene assay. The subcutaneous tumorigenesis in nude mice was conducted to observe the roles of CUX2, KDM5B, and SOX17 in BC tumor growth in vivo.ResultsCUX2 and KDM5B were highly expressed while SOX17 had low expression in BC. Inhibition of CUX2 suppressed BC cell malignant phenotypes. CUX2 promoted KDM5B expression through transcriptional activation, enabling its high expression in BC. KDM5B inhibited SOX17 expression through histone demethylation. Overexpression of KDM5B or downregulation of SOX17 reversed the inhibitory effect of CUX2 downregulation on the malignant behaviors of BC cells. Inhibition of CUX2 impeded BC cell growth in vivo through the KDM5B/SOX17 axis.ConclusionThis study highlights that suppression of CUX2 inhibits KDM5B to repress tumorigenesis and progression of BC through overexpressing SOX17.
      PubDate: Tue, 26 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac110
      Issue No: Vol. 163, No. 9 (2022)
       
  • Sexually Dimorphic Increases in Bone Mass Following Tissue-specific
           Overexpression of Runx1 in Osteoclast Precursors

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      Abstract: AbstractMany metabolic bone diseases arise as a result excessive osteoclastic bone resorption, which has motivated efforts to identify new molecular targets that can inhibit the formation or activity of these bone-resorbing cells. Mounting evidence indicates that the transcription factor Runx1 acts as a transcriptional repressor of osteoclast formation. Prior studies using a conditional knockout approach suggested that Runx1 in osteoclast precursors acts as an inhibitor of osteoclastogenesis; however, the effects of upregulation of Runx1 on osteoclast formation remain unknown. In this study, we investigated the skeletal effects of conditional overexpression of Runx1 in preosteoclasts by crossing novel Runx1 gain-of-function mice (Rosa26-LSL-Runx1) with LysM-Cre transgenic mice. We observed a sex-dependent effect whereby overexpression of Runx1 in female mice increased trabecular bone microarchitectural indices and improved torsion biomechanical properties. These effects were likely mediated by delayed osteoclastogenesis and decreased bone resorption. Transcriptomics analyses during osteoclastogenesis revealed a distinct transcriptomic profile in the Runx1-overexpressing cells, with enrichment of genes related to redox signaling, apoptosis, osteoclast differentiation, and bone remodeling. These data further confirm the antiosteoclastogenic activities of Runx1 and provide new insight into the molecular targets that may mediate these effects.
      PubDate: Tue, 26 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac113
      Issue No: Vol. 163, No. 9 (2022)
       
  • ERK1/2-RSK2 Signaling in Regulation of ERα-Mediated Responses

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      Abstract: AbstractSignaling via extracellular regulated kinase 1/2 (ERK1/2) and p90 ribosomal S6 kinase (RSK), a downstream effector, mediates numerous processes. For example, ERK1/2-RSK signaling is essential for estrogen homeostasis in the mammary gland and uterus to maintain physiological responsiveness. This review will focus on the coordination of ERK1/2-RSK2 and estrogen signaling through estrogen receptor alpha (ERα). The interrelationship and the feedback mechanisms between these pathways occurs at the level of transcription, translation, and posttranslational modification. Identifying how ERK1/2-RSK2 and estrogen signaling cooperate in homeostasis and disease may lead to novel therapeutic approaches in estrogen-dependent disorders.
      PubDate: Tue, 26 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac106
      Issue No: Vol. 163, No. 9 (2022)
       
  • Is E2F1 a Potential Medical Therapy Target for Cushing Disease'

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      Abstract: E2F1Cushing’s diseasecorticotroph adenomatherapy target
      PubDate: Mon, 25 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac117
      Issue No: Vol. 163, No. 9 (2022)
       
  • A Modified Ultra-Sensitive ELISA for Measurement of LH in Mice

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      Abstract: AbstractA major obstacle to monitoring pulsatile luteinizing hormone (LH) secretion in mice has been an assay with sufficient sensitivity in small blood volumes. In 2013, Steyn and colleagues published a highly sensitive enzyme-linked immunosorbent assay (ELISA) that overcame this barrier by coupling a duo of LH antibodies effective in accurately measuring LH in 4-µL whole-blood aliquots. To address the unavailability of the original detection antibody, AFP240580Rb, we validated a replacement detection antibody, biotinylated-5303 SPRN-5, to be used within the established ELISA. This modified LH ELISA demonstrated a minimum detection limit of 0.0028 ng/mL and a limit of quantification of 0.0333 ng/mL or 0.0666 ng/mL in diluted whole-blood samples of volume 6.4 µL (1:10) or 3.2 µL (1:20), respectively. Detection antibody 5303 SPRN-5 demonstrated parallelism, high precision, and accuracy across the standard curve. LH concentrations in comparison assays, using either 5303 SPRN-5 or AFP240580Rb, were highly correlated (R2 = 0.9829) and demonstrated LH pulse profiles from gonadectomized mice that were nearly superimposable. Pulsatile LH secretion was demonstrated in gonad-intact males and diestrous females and basal LH levels measured with 5303 SPRN-5 were approximately 5-fold higher than the limit of quantification. In addition, we document utility of this new LH ELISA to accurately measure LH in whole blood or serum across multiple sampling sites, as well as in pituitary extracts, LβT2 cells, or media. In summary, the modified LH ELISA described here is highly effective in measuring LH across a range of sample types and small volumes in mice.
      PubDate: Sat, 23 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac109
      Issue No: Vol. 163, No. 9 (2022)
       
  • Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to
           Clinical Opportunities

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      Abstract: AbstractOxytocin and vasopressin are peptide hormones secreted from the pituitary that are well known for their peripheral endocrine effects on childbirth/nursing and blood pressure/urine concentration, respectively. However, both peptides are also released in the brain, where they modulate several aspects of social behaviors. Oxytocin promotes maternal nurturing and bonding, enhances social reward, and increases the salience of social stimuli. Vasopressin modulates social communication, social investigation, territorial behavior, and aggression, predominantly in males. Both peptides facilitate social memory and pair bonding behaviors in monogamous species. Here we review the latest research delineating the neural circuitry of the brain oxytocin and vasopressin systems and summarize recent investigations into the circuit-based mechanisms modulating social behaviors. We highlight research using modern molecular genetic technologies to map, monitor activity of, or manipulate neuropeptide circuits. Species diversity in oxytocin and vasopressin effects on social behaviors are also discussed. We conclude with a discussion of the translational implications of oxytocin and vasopressin for improving social functioning in disorders with social impairments, such as autism spectrum disorder.
      PubDate: Thu, 21 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac111
      Issue No: Vol. 163, No. 9 (2022)
       
  • Sex-specific Regulation of Prolactin Secretion by Pituitary Bradykinin
           Receptors

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      Abstract: AbstractSex differences in the control of prolactin secretion are well documented. Sex-related differences in intrapituitary factors regulating lactotroph function have recently attracted attention. Sex differences in prolactinoma development are well documented in clinic, prolactinomas being more frequent in women but more aggressive in men, for poorly understood reasons. Kallikrein, the enzyme releasing kinins has been found in the pituitary, but there is no information on pituitary kinin receptors and their function. In the present work, we characterized pituitary bradykinin receptors (BRs) at the messenger RNA and protein levels in 2 mouse models of prolactinoma, Drd2 receptor gene inactivation and hCGβ gene overexpression, in both males and females, wild type or genomically altered. BR B2 (B2R) accounted for 97% or more of total pituitary BRs in both models, regardless of genotype, and was present in lactotrophs, somatotrophs, and gonadotrophs. Male pituitaries displayed higher level of B2R than females, regardless of genotype. Pituitary B2R gene expression was downregulated by estrogen in both males and females but only in females by dopamine. Activation of B1R or B2R by selective pharmacological agonists induced prolactin release in male pituitaries but inhibited prolactin secretion in female pituitaries. Increased B2R content was observed in pituitaries of mutated animals developing prolactinomas, compared to their respective wild-type controls. The present study documents a novel sex-related difference in the control of prolactin secretion and suggests that kinins are involved, through B2R activation, in lactotroph function and prolactinoma development.
      PubDate: Thu, 21 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac108
      Issue No: Vol. 163, No. 9 (2022)
       
  • Follicular Hyperstimulation Dysgenesis: New Explanation for Adverse
           Effects of Excessive FSH in Ovarian Stimulation

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      Abstract: AbstractHigh follicle-stimulating hormone (FSH) doses during ovarian stimulation protocols for assisted reproductive technologies (ART) are detrimental to ovulatory follicle function and oocyte quality. However, the mechanisms are unclear. In a small ovarian reserve heifer model, excessive FSH doses lead to phenotypic heterogeneity of ovulatory size follicles, with most follicles displaying signs of premature luteinization and a range in severity of abnormalities. By performing whole transcriptome analyses of granulosa cells, cumulus cells, and oocytes from individual follicles of animals given standard or excessive FSH doses, we identified progressive changes in the transcriptomes of the 3 cell types, with increasing severity of follicular abnormality with the excessive doses. The granulosa and cumulus cells each diverged progressively from their normal phenotypes and became highly similar to each other in the more severely affected follicles. Pathway analysis indicates a possible dysregulation of the final stages of folliculogenesis, with processes characteristic of ovulation and luteinization occurring concurrently rather than sequentially in the most severely affected follicles. These changes were associated with disruptions in key pathways in granulosa and cumulus cells, which may account for previously reported reduced estradiol production, enhanced progesterone and oxytocin production and diminished ovulation rates. Predicted deficiencies in oocyte survival, stress response, and fertilization suggest likely reductions in oocyte health, which could further compromise oocyte quality and ART outcomes.
      PubDate: Thu, 14 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac100
      Issue No: Vol. 163, No. 9 (2022)
       
  • Mitotane Targets Lipid Droplets to Induce Lipolysis in Adrenocortical
           Carcinoma

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      Abstract: AbstractIntroductionAdrenocortical carcinoma (ACC) is a rare aggressive cancer with low overall survival. Adjuvant mitotane improves survival but is limited by poor response rates and resistance. Mitotane’s efficacy is attributed to the accumulation of toxic free cholesterol, predominantly through cholesterol storage inhibition. However, targeting this pathway has proven unsuccessful. We hypothesize that mitotane-induced free-cholesterol accumulation is also mediated through enhanced breakdown of lipid droplets.MethodologyATCC-H295R (mitotane-sensitive) and MUC-1 (mitotane-resistant) ACC cells were evaluated for lipid content using specific BODIPY dyes. Protein expression was evaluated by immunoblotting and flow cytometry. Cell viability was measured by quantifying propidium iodide-positive cells following mitotane treatment and pharmacological inhibitors of lipolysis.ResultsH295R and MUC-1 cells demonstrated similar neutral lipid droplet numbers at baseline. However, evaluation of lipid machinery demonstrated distinct profiles in each model. Analysis of intracellular lipid droplet content showed H295R cells preferentially store cholesteryl esters, whereas MUC-1 cells store triacylglycerol. Decreased lipid droplets were associated with increased lipolysis in H295R and in MUC-1 at toxic mitotane concentrations. Pharmacological inhibition of lipolysis attenuated mitotane-induced toxicity in both models.ConclusionWe highlight that lipid droplet breakdown and activation of lipolysis represent a putative additional mechanism for mitotane-induced cytotoxicity in ACC. Further understanding of cholesterol and lipids in ACC offers potential novel therapeutic exploitation, especially in mitotane-resistant disease.
      PubDate: Thu, 07 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac102
      Issue No: Vol. 163, No. 9 (2022)
       
  • Regulatory T Cell Proportion and Phenotype Are Altered in Women Using Oral
           Contraception

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      Abstract: AbstractRegulatory T (Treg) cells are a specialized CD4+ T cell subpopulation that are essential for immune homeostasis, immune tolerance, and protection against autoimmunity. There is evidence that sex-steroid hormones estrogen and progesterone modulate Treg cell abundance and phenotype in women. Since natural oscillations in these hormones are modified by hormonal contraceptives, we examined whether oral contraception (OC) use impacts Treg cells and related T cell populations. T cells were analyzed by multiparameter flow cytometry in peripheral blood collected across the menstrual cycle from healthy women either using OC or without hormonal contraception and from age-matched men. Compared to naturally cycling women, women using OC had fewer Treg cells and an altered Treg cell phenotype. Notably, Treg cells exhibiting a strongly suppressive phenotype, defined by high FOXP3, CD25, Helios, HLADR, CTLA4, and Ki67, comprised a lower proportion of total Treg cells, particularly in the early- and mid-cycle phases. The changes were moderate compared to more substantial differences in Treg cells between women and men, wherein women had fewer Treg cells—especially of the effector memory Treg cell subset—associated with more T helper type 1 (Th1) cells and CD8+ T cells and lower Treg:Th1 cell and Treg:CD8+ T cell ratios than men. These findings imply that OC can modulate the number and phenotype of peripheral blood Treg cells and raise the possibility that Treg cells contribute to the physiological changes and altered disease susceptibility linked with OC use.
      PubDate: Mon, 04 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac098
      Issue No: Vol. 163, No. 9 (2022)
       
  • Distinctions in PCOS Induced by Letrozole Vs Dehydroepiandrosterone With
           High-fat Diet in Mouse Model

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      Abstract: AbstractPolycystic ovarian syndrome (PCOS) is a complex health condition associated with metabolic disturbances and infertility. Recent data suggest that the prevalence of PCOS is increasing among women globally, although the etiology of these trends is undefined. Consequently, preclinical models that better reflect the biology of PCOS are urgently needed to facilitate research that can lead to the discovery of prevention strategies or improved management. The existing animal models have several limitations as they do not reflect all the PCOS features metabolically and/or phenotypically. Therefore, there is no clear consensus on the use of appropriate animal model and selection of the most appropriate PCOS-inducing agent. To that end, we have established a Swiss albino mouse model of PCOS based on 3 weeks of daily treatment with letrozole (50 μg/day; intraperitoneal) and dehydroepiandrosterone (DHEA, 6 mg/100 g body weight; subcutaneous) in 5-week-old female mice fed on normal or high-fat diet (HFD). Mice were regularly assessed for body weight, blood glucose, and estrous cycle. Three weeks after drug administration, mice were sacrificed and assessed for blood-based metabolic parameters as well as ovarian function. Our results indicate that DHEA combined with HFD produces changes mimicking those of clinical PCOS, including elevated serum testosterone and luteinizing hormone, dyslipidemia, poor ovarian microenvironment, and development of multiple ovarian cysts, recapitulating cardinal features of PCOS. In comparison, normal diet and/or letrozole produced fewer features of PCOS. The data from the experimental models presented here can improve our understanding of PCOS, a growing concern in women’s health.
      PubDate: Fri, 01 Jul 2022 00:00:00 GMT
      DOI: 10.1210/endocr/bqac097
      Issue No: Vol. 163, No. 9 (2022)
       
 
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