Androstenedione changes steroidogenic activity of SGBS cells

The rapid increase of obesity during the last decades and its future prospects are alarming. Besides the general discussed causes of obesity, the ‘Developmental Origins of Health and Disease’ (DOHaD) hypothesis received more attention in recent years. This hypothesis postulates an adverse influence during early development that programs the unborn child for metabolic dysfunctions later in life. Childhood obesity – an as much increasing problem – can be predisposed by maternal overweight and diabetes. Both, obesity and hyperinsulinemia are major causes of female hyperandrogenemia. As predicted by the DOHaD hypothesis and shown in animal models, developmental androgen excess can lead to metabolic abnormalities in offspring. In this study, we investigated, if androgen exposure adversely affects the adipogenic differentiation of preadipocytes and the endocrine function of adult adipocytes. The human SGBS preadipocyte model was used to affirm the de novo biosynthesis of steroid hormones under normal adipogenesis conditions. Normal adipogenesis was paralleled by an increase of corticosteroids and androgens, whereas estrogen remained at a steady level. Treatment with androstenedione had no effect on SGBS proliferation and differentiation, but adult adipocytes exhibited a significant higher accumulation of triglycerides. Progesterone (up to 2-fold), testosterone (up to 38-fold) and cortisone (up to 1.4-fold) – but not cortisol – were elevated by androstenedione administration in adult adipocytes. Estrogen was not altered. Data suggest that androgen does not negatively influence adipogenic differentiation, but steroidogenic function of SGBS adipocytes.

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Gordon syndrome caused by a CUL3 mutation in a patient with short stature in Korea: a case report

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0361 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Ji Hong Park ◽

Ji Hyun Kim ◽

Yo Han Ahn ◽

Hee Gyung Kang ◽

Il Soo Ha ◽

...

Keyword(s):

Metabolic Acidosis ◽

Short Stature ◽

De Novo ◽

Plasma Renin ◽

Endocrine Function ◽

First Case ◽

Pseudohypoaldosteronism Type Ii ◽

Stimulation Tests ◽

Severity Of The Disease ◽

Potassium Gradient

Abstract Objectives: Gordon syndrome (GS), also known as pseudohypoaldosteronism type II, is a rare tubular disease characterized by hypertension, hyperkalemia, and metabolic acidosis. Its causative genes are CUL3, KLHL3, WNK1, and WNK4, and they are associated with varying severity of the disease. Herein, we report the first case of GS caused by a CUL3 mutation in a patient with short stature in Korea.Case presentation: A 7-year-old boy had hypertension, metabolic acidosis, and persistent hyperkalemia, which were initially detected during the evaluation of short stature. He was born small for gestational age at late preterm gestation. Laboratory test findings showed hyperkalemia with low trans-tubular potassium gradient, hyperchloremic metabolic acidosis with a normal anion gap, and low plasma renin levels. Genetic analysis revealed a heterozygous de novo mutation in the CUL3 gene (c.1377+1G > C in intron 9). Thus, a diagnosis of GS was made. The results of the endocrine function test (including growth hormone stimulation tests) were normal. After thiazide treatment, the patient’s electrolyte levels were normalized. However, he presented with persistent hypertension and short stature.Conclusions: GS should be considered in children with short stature, hypertension, and hyperkalemia, and early treatment may reduce complications.

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A previously undescribed highly prevalent phage identified in a Danish enteric virome catalogue

10.21203/rs.3.rs-273865/v1 ◽

2021 ◽

Author(s):

Lore Van Espen ◽

Emilie Glad Bak ◽

Leen Beller ◽

Lila Close ◽

Ward Deboutte ◽

...

Keyword(s):

Viral Genome ◽

De Novo ◽

Human Gut ◽

Host Genus ◽

Faecal Samples ◽

High Prevalence ◽

Paediatric Cohort ◽

Health And Disease ◽

Wet Lab ◽

Public Datasets

Abstract Background: Gut viruses are important players in the complex human gut microbial ecosystem. Recently, the number of human gut virome studies is steadily increasing, however we are still only scratching the surface of the immense viral diversity as many wet lab and bio-informatics challenges remain. In this study, 254 virus-enriched faecal metagenomes from 204 Danish subjects were used to generate a Danish Enteric Virome Catalogue (DEVoC) of 12,986 non-redundant viral genome sequences encoding 190,029 viral genes, which formed 67,921 orthologous groups. The DEVoC was used to characterize the composition of the healthy DEVoC gut viromes from 46 children and adolescents (6-18 years old) and 45 adults (40 -73 years old).Results: The majority of DEVoC viral sequences (67.3 %) and proteins (61.6 %) were not present in other (human gut) viral genome databases. Gut viromes of healthy Danish subjects mostly consisted of phages. While 39 phage genomes (PGs) were present in more than 10 healthy subjects, the degree of viral individuality was high. Among the 39 prevalent PGs, one was significantly more prevalent in the paediatric cohort, whereas two were more prevalent in adults. In 1,880 gut virome samples of 27 studies from across the world, the 39 prevalent PGs reveal several age-, geography- and disease-related prevalence patterns. Two PGs also showed a remarkably high prevalence worldwide – a crAss-like phage (20.6% prevalence), belonging to the tentative AlphacrAssvirinae subfamily, genus I; and a previously undescribed circular temperate phage (14.4% prevalence), named LoVEphage (because it encodes Lots of Viral Elements). A de novo assembly of selected public datasets generated an additional 18 circular LoVEphage-like genomes (67.9-72.4 kb). CRISPR spacer analysis suggested Bacteroides as a host genus for the LoVEphage, and a closely related prophage was identified in Bacteroides dorei, further confirming the host.Conclusions: The DEVoC, the largest human gut virome catalogue generated from consistently processed faecal samples, facilitated analysis of healthy Danish human gut viromes and we foresee that it will benefit future analysis on the roles of gut viruses in human health and disease. The identification of a previously undescribed prevalent phage illustrates the usefulness of developing a virome catalogue.

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Role of 1α,25-Dihydroxyvitamin D3 in Adipogenesis of SGBS Cells: New Insights into Human Preadipocyte Proliferation

Cellular Physiology and Biochemistry ◽

10.1159/000491770 ◽

2018 ◽

Vol 48 (1) ◽

pp. 397-408 ◽

Cited By ~ 8

Author(s):

Ingrid Felicidade ◽

Daniele Sartori ◽

Susan L.M. Coort ◽

Simone Cristine Semprebon ◽

Andressa Megumi Niwa ◽

...

Keyword(s):

Gene Expression ◽

Vitamin D ◽

Adipose Tissue ◽

Lipid Content ◽

Cell Model ◽

Adipogenic Differentiation ◽

Growth Arrest ◽

Proliferation And Differentiation ◽

Sgbs Cells

Background/Aims: Compared with non-obese individuals, obese individuals commonly store more vitamin D in adipose tissue. VDR expression in adipose tissue can influence adipogenesis and is therefore a target pathway deserving further study. This study aims to assess the role of 1,25(OH)2D3 in human preadipocyte proliferation and differentiation. Methods: RTCA, MTT, and trypan blue assays were used to assess the effects of 1,25(OH)2D3 on the viability, proliferation, and adipogenic differentiation of SGBS cells. Cell cycle and apoptosis analyses were performed with flow cytometry, triglycerides were quantified, and RT-qPCR was used to assess gene expression. Results: We confirmed that the SGBS cell model is suitable for studying adipogenesis and demonstrated that the differentiation protocol induces cell maturation, thereby increasing the lipid content of cells independently of treatment. 1,25(OH)2D3 treatment had different effects according to the cell stage, indicating different modes of action driving proliferation and differentiation. In preadipocytes, 1,25(OH)2D3 induced G1 growth arrest at both tested concentrations without altering CDKN1A gene expression. Treatment with 100 nM 1,25(OH)2D3 also decreased MTT absorbance and the lipid concentration. Moreover, increased normalized cell index values and decreased metabolic activity were not induced by proliferation or apoptosis. Exposure to 100 nM 1,25(OH)2D3 induced VDR, CEBPA, and CEBPB expression, even in the preadipocyte stage. During adipogenesis, 1,25(OH)2D3 had limited effects on processes such as VDR and PPARG gene expression, but it upregulated CEBPA expression. Conclusions: We demonstrated for the first time that 1,25(OH)2D3 induces changes in preadipocytes, including VDR expression and growth arrest, and increases the lipid content in adipocytes treated for 16 days. Preadipocytes are important cells in adipose tissue homeostasis, and understanding the role of 1,25(OH)2D3 in adipogenesis is a crucial step in ensuring adequate vitamin D supplementation, especially for obese individuals.

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Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa852 ◽

2020 ◽

Author(s):

Cecilie Melau ◽

John E Nielsen ◽

Signe Perlman ◽

Lene Lundvall ◽

Lea Langhoff Thuesen ◽

...

Keyword(s):

De Novo ◽

Culture Media ◽

Ex Vivo ◽

Disorders Of Sex Development ◽

Endocrine Function ◽

Specific Response ◽

Adrenal Tissue ◽

Sex Development ◽

Adrenal Steroidogenesis ◽

Novel Approach

Abstract Context Disorders affecting adrenal steroidogenesis promote an imbalance in the normally tightly controlled secretion of mineralocorticoids, glucocorticoids, and androgens. This may lead to differences/disorders of sex development in the fetus, as seen in virilized girls with congenital adrenal hyperplasia (CAH). Despite the important endocrine function of human fetal adrenals, neither normal nor dysregulated adrenal steroidogenesis is understood in detail. Objective Due to significant differences in adrenal steroidogenesis between human and model species (except higher primates), we aimed to establish a human fetal adrenal model that enables examination of both de novo and manipulated adrenal steroidogenesis. Design and Setting Human adrenal tissue from 54 1st trimester fetuses were cultured ex vivo as intact tissue fragments for 7 or 14 days. Main Outcome Measures Model validation included examination of postculture tissue morphology, viability, apoptosis, and quantification of steroid hormones secreted to the culture media measured by liquid chromatography-tandem mass spectrometry. Results The culture approach maintained cell viability, preserved cell populations of all fetal adrenal zones, and recapitulated de novo adrenal steroidogenesis based on continued secretion of steroidogenic intermediates, glucocorticoids, and androgens. Adrenocorticotropic hormone and ketoconazole treatment of ex vivo cultured human fetal adrenal tissue resulted in the stimulation of steroidogenesis and inhibition of androgen secretion, respectively, demonstrating a treatment-specific response. Conclusions Together, these data indicate that ex vivo culture of human fetal adrenal tissue constitutes a novel approach to investigate local effects of pharmaceutical exposures or emerging therapeutic options targeting imbalanced steroidogenesis in adrenal disorders, including CAH.

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C-type natriuretic peptide in reproduction, pregnancy and fetal development

Journal of Endocrinology ◽

10.1677/joe.0.1800017 ◽

2004 ◽

Vol 180 (1) ◽

pp. 17-22 ◽

Cited By ~ 39

Author(s):

T Walther ◽

H Stepan

Keyword(s):

Natriuretic Peptide ◽

Fetal Development ◽

De Novo ◽

Biological Effects ◽

Endocrine Function ◽

Comprehensive Overview ◽

Specific Expression ◽

Embryonic And Fetal Development ◽

Organ Specific ◽

Reproductive Processes

C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family that consists of three structurally related peptides with a 17-amino acid ring linked by a disulfide bond. In contrast to atrial and brain natriuretic peptides that are mainly cardiovascular hormones, CNP acts predominantly in an autocrine/paracrine fashion, is commonly considered to be an endothelial hormone with antimitogenic properties, and is characterized as a regulator of endochondral ossification. Its biological effects are mediated by an intracellular cGMP accumulation via specific membrane-bound guanylyl cyclase B (GC-B) activation. There is growing evidence that this peptide is also involved in various reproductive processes as well as in embryonic and fetal development. In rodents, CNP and its receptor are highly expressed in the uterus and ovaries with specific regulation during the estrous cycle. During pregnancy, CNP mRNA is detectable in mice embryos and shows an organ-specific expression in maternal reproductive tIssues with the highest concentration in the placenta. This could indicate a defined biological function of the CNP/GC-B/cGMP axis in gestation e.g. antagonizing vasoconstrictive peptides like angiotensin II. In humans, besides a postulated fetal de novo synthesis of CNP, both the peptide and its receptor are expressed in the placenta and myometrium with opposite regulation of CNP in pregnancies complicated by pre-eclampsia or intrauterine growth retardation. Since the maternal plasma levels do not reflect these alterations, one can conclude that this part of the natriuretic peptide system acts locally suggesting that CNP-stimulated cGMP release exhibits organ-specific effects. Importantly, CNP has also become a peptide with a distinct role in male reproductive processes, since endocrine function of the testis and the regulation of penile erection are regulated by the CNP/GC-B axis. This review gives a comprehensive overview of the multiple functions of CNP in reproduction and pregnancy as well as in embryonic and fetal development.

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Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00837.2009 ◽

2010 ◽

Vol 299 (3) ◽

pp. R728-R739 ◽

Cited By ~ 123

Author(s):

Barbara E. Hasek ◽

Laura K. Stewart ◽

Tara M. Henagan ◽

Anik Boudreau ◽

Natalie R. Lenard ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Homeostasis ◽

De Novo ◽

Uncoupling Protein ◽

Nutrient Sensing ◽

De Novo Lipogenesis ◽

Endocrine Function ◽

Fischer 344 ◽

Methionine Restriction ◽

Heat Increment

Dietary methionine restriction (MR) is a mimetic of chronic dietary restriction (DR) in the sense that MR increases rodent longevity, but without food restriction. We report here that MR also persistently increases total energy expenditure (EE) and limits fat deposition despite increasing weight-specific food consumption. In Fischer 344 (F344) rats consuming control or MR diets for 3, 9, and 20 mo, mean EE was 1.5-fold higher in MR vs. control rats, primarily due to higher EE during the night at all ages. The day-to-night transition produced a twofold higher heat increment of feeding (3.0°C vs. 1.5°C) in MR vs. controls and an exaggerated increase in respiratory quotient (RQ) to values greater than 1, indicative of the interconversion of glucose to lipid by de novo lipogenesis. The simultaneous inhibition of glucose utilization and shift to fat oxidation during the day was also more complete in MR (RQ ∼0.75) vs. controls (RQ ∼0.85). Dietary MR produced a rapid and persistent increase in uncoupling protein 1 expression in brown (BAT) and white adipose tissue (WAT) in conjunction with decreased leptin and increased adiponectin levels in serum, suggesting that remodeling of the metabolic and endocrine function of adipose tissue may have an important role in the overall increase in EE. We conclude that the hyperphagic response to dietary MR is matched to a coordinated increase in uncoupled respiration, suggesting the engagement of a nutrient-sensing mechanism, which compensates for limited methionine through integrated effects on energy homeostasis.

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Phenotypic and Cytogenetic Characterization of Mesenchymal Stromal Cells inDe NovoMyelodysplastic Syndromes

Analytical Cellular Pathology ◽

10.1155/2016/8012716 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11

Author(s):

A. J. I. S. Rathnayake ◽

H. W. W. Goonasekera ◽

V. H. W. Dissanayake

Keyword(s):

Stromal Cells ◽

De Novo ◽

Adipogenic Differentiation ◽

Growth Curves ◽

Population Doubling ◽

Differentiation Potential ◽

Growth Properties ◽

Control Mscs ◽

Growth Differences

Bone marrow (BM) mesenchymal stem/stromal cells (MSCs) are vital in hematopoiesis. Whether BM-MSCs alter their characteristics in Myelodysplastic Syndromes (MDS) is still controversial. We characterized MSCs ofde novoMDS patients in Sri Lanka who have not been reported previously in the literature. We also analyzed MSCs derived from different MDS subtypes. MSCs were culture-expanded, characterized by flow cytometry, and induced towards osteogenic and adipogenic differentiation. Growth properties were determined using growth curves and population doubling times. Karyotyping and FISH were performed on MSCs. Cell morphology, differentiation potential, and CD marker expression of MDS-MSCs of all subtypes were comparable to those of control-MSCs. No significant growth differences were observed between control MSCs and MDS-MSCs of all subtypes (p>0.05). 31% of MDS-MSCs had chromosomal aberrations (der(3),del(6q),del(7p), loss of chromosomes) whose BM karyotypes were normal. Highest percentage of karyotypic abnormalities was observed in RCMD-MSCs. Patients with abnormal BM karyotypes had no aberrant MSC clones. Results show that in spite of presence of genetically abnormal clones in MDS-MSC populations,in vitrophenotypic and growth characteristics of MSCs in MDS remain unchanged. Further, the occurrence of genetic abnormalities in BM-MSCs in MDS could be considered as an autonomous event from that of their hematopoietic counterparts.

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NCOG-53. PREDICTORS OF ENDOCRINE OUTCOME AFTER ENDOSCOPIC TRANSSPHENOIDAL SURGERY FOR NON-FUNCTIONING PITUITARY ADENOMAS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.591 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii141-ii141

Author(s):

Jenie Hwang ◽

Diane Yum ◽

Michael Chicoine ◽

Ralph Dacey ◽

Joshua Osbun ◽

...

Keyword(s):

Pituitary Adenomas ◽

Transsphenoidal Surgery ◽

De Novo ◽

Postoperative Recovery ◽

Endocrine Function ◽

Male Hypogonadism ◽

Endoscopic Transsphenoidal Surgery ◽

Thyroid Axis ◽

Negative Predictor ◽

New Onset

Abstract BACKGROUND Although endoscopic transsphenoidal surgery (ETSS) is an established treatment for patients with nonfunctioning pituitary adenomas (NFPAs), data are limited regarding the rates and predictors of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS. OBJECTIVE To analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. METHODS Among a cohort of 601 consecutive patients who underwent ETSS for NFPA between 2010 and 2018 at Washington University in Saint Louis, recovery or development of new hypopituitarism was retrospectively analyzed in 209 patients. RESULTS Preoperative endocrine deficits were observed in 59.8% of patients (125/209), and the deficit rates were 76.8% for male gonadal axis (86/112), 42.5% for thyroid axis, 25.8% for growth hormone axis, and 15.8% for cortisol axis. Recovery of preoperative pituitary deficit was noted in all four axes, with highest recovery in the cortisol axis with a 1-year cumulative recovery rate of 44.3%. New-onset postoperative hypopituitarism occurred most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Multivariate analyses revealed axis-specific predictors of postoperative recovery and de novo deficiency. Older age was a negative predictor for recovery of both male hypogonadism (P= 0.04) and adrenal insufficiency (P=0.046), and a larger tumor volume was a negative predictor for recovery of hypothyroidism (P=0.043). Although higher body mass index was generally associated with any new postoperative pituitary deficit (P=0.03), most predictors of new onset deficits also differed by hormone axis. CONCLUSIONS Dynamic changes in pituitary hormonal levels were observed in a significant fraction of patients following ETSS in NFPA patients. The specific hormonal axis dictated postoperative endocrine vulnerability, recovery, and predictors of recovery or loss of endocrine function.

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New insights into the generation and role of de novo mutations in health and disease

Genome Biology ◽

10.1186/s13059-016-1110-1 ◽

2016 ◽

Vol 17 (1) ◽

Cited By ~ 169

Author(s):

Rocio Acuna-Hidalgo ◽

Joris A. Veltman ◽

Alexander Hoischen

Keyword(s):

De Novo ◽

De Novo Mutations ◽

Health And Disease

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Neurosteroids and GABAergic signaling in health and disease

BioMolecular Concepts ◽

10.1515/bmc-2012-0033 ◽

2013 ◽

Vol 4 (1) ◽

pp. 29-42 ◽

Cited By ~ 28

Author(s):

Georgina MacKenzie ◽

Jamie Maguire

Keyword(s):

Sexual Behaviors ◽

Neuronal Excitability ◽

De Novo ◽

Aminobutyric Acid ◽

Acid Type ◽

Direct Binding ◽

Health And Disease ◽

Local Metabolism ◽

The Brain ◽

Large Charge

AbstractEndogenous neurosteroids such as allopregnanolone, allotetrahydrodeoxycorticosterone, and androstanediol are synthesized either de novo in the brain from cholesterol or are generated from the local metabolism of peripherally derived progesterone or corticosterone. Fluctuations in neurosteroid concentrations are important in the regulation of a number of physiological responses including anxiety and stress, reproductive, and sexual behaviors. These effects are mediated in part by the direct binding of neurosteroids to γ-aminobutyric acid type-A receptors (GABAARs), resulting in the potentiation of GABAAR-mediated currents. Extrasynaptic GABAARs containing the δ subunit, which contribute to the tonic conductance, are particularly sensitive to low nanomolar concentrations of neurosteroids and are likely their preferential target. Considering the large charge transfer generated by these persistently open channels, even subtle changes in neurosteroid concentrations can have a major impact on neuronal excitability. Consequently, aberrant levels of neurosteroids have been implicated in numerous disorders, including, but not limited to, anxiety, neurodegenerative diseases, alcohol abuse, epilepsy, and depression. Here we review the modulation of GABAAR by neurosteroids and the consequences for health and disease.

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