scholarly journals Basic Concepts of Inborn Errors and Defects of Steroid Biosynthesis

PEDIATRICS ◽  
1967 ◽  
Vol 40 (3) ◽  
pp. 476-476
Author(s):  
JOHN F. CRIGLER
Keyword(s):  
Steroid Hormone ◽  
Clinical Manifestations ◽  
Short Paper ◽  
Adrenal Hyperplasia ◽  
Steroid Biosynthesis ◽  
Inborn Errors ◽  
The Third ◽  
Back Volume ◽  
Hormone Biosynthesis ◽  
Biochemical Abnormalities

This short, paper-back volume summarizes the Proceedings of the Third Symposium of the Society for the Study of Inborn Errors of Metabolism which was held in Birmingham, England, in October 1965. As the title implies, a major portion of the symposium was devoted to the presentation of current views on the group of inborn errors that lead to defects in steroid hormone biosynthesis. The four papers on that general subject are largely in the nature of reviews of the clinical manifestations (Prof. D. V. Hubble) and biochemical abnormalities of cortisol (R. W. H. Edwards), androgens (O. M. Galal and B. T. Rudd), and aldosterone biosynthesis (H. K. A. Visser) in patients with congenital adrenal hyperplasia.

scholarly journals Reversible infertility in a liver receptor homologue-1 (LRH-1)-knockdown mouse model

2014 ◽  
Vol 26 (2) ◽  
pp. 293 ◽  
Author(s):  
Han Gerrits ◽  
Marc C. B. C. Paradé ◽  
Annemie M. C. B. Koonen-Reemst ◽  
Nicole E. C. Bakker ◽  
Lenita Timmer-Hellings ◽  
...  
Keyword(s):  
Mouse Model ◽  
Steroid Hormone ◽  
Orphan Nuclear Receptor ◽  
Steroid Biosynthesis ◽  
Shrna Expression ◽  
Plasma Progesterone ◽  
Contraceptive Therapy ◽  
Hormone Biosynthesis ◽  
In Vivo Induction

Liver receptor homologue-1 (LRH-1) is an orphan nuclear receptor that has been implicated in steroid hormone biosynthesis and fertility. Herein we describe a transgenic inducible short hairpin (sh) RNA mouse model that was used to study the effect of transient LRH-1 knockdown in vivo. Induction of expression of the shRNA directed against LRH-1 for 2–6 weeks resulted in 80% knockdown of LRH-1 protein in the ovary and complete infertility. Gonadotropin hyperstimulation could not rescue the observed defects in ovulation and corpus luteum formation in LRH-1-knockdown mice. The infertility phenotype was fully reversible because LRH-1-knockdown females became pregnant and delivered normal size litters and healthy pups after cessation of LRH-1 shRNA expression. Timed ovarian microarray analysis showed that, in line with the observed decrease in plasma progesterone levels, key steroid biosynthesis genes, namely Star, Cyp11a1, Hsd3b and Scarb1, were downregulated in LRH-1-knockdown ovaries. In contrast with what has been described previously, no clear effect was observed on oestrogenic activity in LRH-1-knockdown mice. Only Sult1e1 and, surprisingly, Hsd17b7 expression was modulated with potentially opposite effects on oestradiol bioavailability. In conclusion, the fully reversible infertility phenotype of LRH-1-knockdown mice shows the feasibility of an LRH-1 antagonist as new contraceptive therapy with a mechanism of action that most prominently affects cholesterol availability and progesterone production.

scholarly journals 106 Randel Lecture: The history of the discovery of the Steroidogenic Acute Regulatory (StAR) Protein

2019 ◽  
Vol 97 (Supplement_1) ◽  
pp. 39-39
Author(s):  
Douglas M Stocco
Keyword(s):  
Mitochondrial Membrane ◽  
Steroid Hormone ◽  
Conditional Knockout ◽  
Mitochondrial Outer Membrane ◽  
Inner Mitochondrial Membrane ◽  
Steroid Biosynthesis ◽  
Steroid Synthesis ◽  
Steroid Hormone Biosynthesis ◽  
Star Protein ◽  
Hormone Biosynthesis

Abstract This two-part presentation regarding acute regulation of steroid biosynthesis documents discovery of the StAR protein and resolves controversy regarding mitochondrial cholesterol transport. The acute regulation of steroid biosynthesis was known to require de novo synthesis of a regulator protein to mediate the transfer of cholesterol, the substrate for steroids, from the outer to the inner mitochondrial membrane where it was converted to pregnenolone by the cytochrome P450 side chain cleavage enzyme. We discovered a novel protein that was tightly correlated with steroid biosynthesis and had the requisite characteristics for the putative acute regulator of cholesterol transfer for steroid synthesis. Further studies confirmed that StAR protein is an indispensable component in the process of mitochondrial uptake of the cholesterol substrate for steroidogenesis. The translocator protein (TSPO) is a mitochondrial outer membrane protein suggested to import cholesterol to the inner mitochondrial membrane. However, it was demonstrated in vivo in Leydig cell specific TSPO conditional knockout mice that TSPO was not required for testosterone production or fertility. Similarly, global TSPO knockout (TSPO/-) mice were viable and fertile with fecundity equivalent to TSPO floxed (TSPOfl/fl) controls. Adrenal and gonadal steroidogenesis did not differ between TSPOfl/ fl and TSPO-/- mice. In vitro use of different steroidogenic cell line models (MA-10, MLTC, Y-1, H295R and R2C) demonstrated that siRNA-knockdown of TSPO did not affect steroidogenesis. Also, CRISPR/ Cas9-mediated TSPO deletion did not affect MA-10 cell steroidogenesis. These results directly 1) refute the suggestion that TSPO is indispensable for viability and steroid hormone biosynthesis; and, 2) substantiate the primal role of the StAR protein as the rate limiting factor in steroid hormone biosynthesis.

Update on adrenal steroid hormone biosynthesis and clinical implications

2019 ◽  
Vol 104 (12) ◽  
pp. 1223-1228 ◽  
Author(s):  
Irina-Alexandra Bacila ◽  
Charlotte Elder ◽  
Nils Krone
Keyword(s):  
Clinical Implications ◽  
Steroid Biosynthesis ◽  
Hydroxylase Deficiency ◽  
Inborn Errors ◽  
Mortality And Morbidity ◽  
Adrenal Steroid ◽  
Adrenal Steroidogenesis ◽  
Complex Process ◽  
Hormone Biosynthesis ◽  
21 Hydroxylase Deficiency

Steroid biosynthesis is a complex process in which cholesterol is converted to steroid hormones with the involvement of multiple enzymes and cofactors. Inborn conditions affecting adrenal steroidogenesis are relatively common in paediatric practice and have serious implications on patient mortality and morbidity. This paper provides an overview of novel insights into human adrenal steroid biosynthesis. Inborn errors of steroidogenesis associated with congenital adrenal hyperplasia are discussed, with a particular focus on the pathophysiology and clinical features of 21-hydroxylase deficiency. The final section of the review presents more recent findings and clinical implications of adrenal-specific androgen biosynthesis.

Inborn Errors of Metabolism

1980 ◽  
Vol 2 (6) ◽  
pp. 175-181
Author(s):  
George M. Komrower
Keyword(s):  
Neurospora Crassa ◽  
Inborn Error ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Homogentisic Acid ◽  
Turn Of The Century ◽  
Inborn Errors ◽  
The Family ◽  
The One ◽  
Biochemical Abnormalities

Around the turn of the century Garrard established the concept of an inborn error of metabolism using his study on alcaptonuria to exemplify his hypothesis that a considerable number of metabolic disorders with clearly defined clinical, pathologic, and biochemical abnormalities arise because an enzyme governing a single metabolic step is either reduced in activity or missing altogether. He pointed out the familial distribution of alcaptonuria and later showed that the inheritance could be explained on mendelian principles, ie, the affected individual was homozygous for the abnormal gene and that the inheritance was recessive, both parents being heterozygous for the disorder. He suggested that the accumulation of homogentisic acid in alcaptonuria was evidence that this substance is a normal metabolite in the degradation of tyrosine and attributed this accumulation to a failure of oxidation of homogentisic acid. In addition to alcaptonuria he described cystinunia, pentosuria, and albinism. This work was the forerunner of the classic studies of Beadle and Tatum on mutants of Neurospora crassa which led to the one gene-one enzyme concept. DETECTION Different groups require special attention: the family at risk because of previously affected individuals, those with unusual features suggestive of metabolic disorders, and sick newborns. Screening of normal newborns requires a different approach.

COLLOID CYSTS OF THE THIRD VENTRICLE: A REVIEW OF SIXTEEN CASES

2021 ◽  
pp. 62-64
Author(s):  
Y Srinivas Rao ◽  
Hemal Chheda ◽  
Ch Surendra ◽  
M V Vijayasekhar ◽  
K Satya Varaprasad
Keyword(s):  
Benign Lesion ◽  
Third Ventricle ◽  
Clinical Manifestations ◽  
Colloid Cyst ◽  
Surgical Approaches ◽  
Imaging Features ◽  
Complete Excision ◽  
Advantages And Disadvantages ◽  
The Third ◽  
Colloid Cysts

BACKGROUND : Colloid cysts are one of the rare brain tumours and are mostly located in the anterosuperior portion of the third ventricle, between the fornix and surround of Foramen of Monroe. OBJECTIVES: Ÿ 1.To review the demographic information & analyse clinical manifestations of patients presenting with colloid cyst of third ventricle. Ÿ 2.To analyze the advantages and disadvantages of various surgical approaches Ÿ 3.To assess the surgical outcome in colloid cyst patients operated by any method. MATERIALS AND METHODS: A retrospective study was performed on 16 patients who presented with a colloid cyst and underwent surgery at the Department of Neurosurgery, King George Hospital, Andhra Medical College between 2013-2018. They were evaluated based on clinical ndings and imaging features, surgical approaches used for resection and their outcomes. RESULTS: Sixteen cases of colloid cyst of the third ventricle were operated upon between 2013-2018. There were seven male and nine female patients with their ages varying between 9 and 62 years old. Nine patients were operated on by using a transcortical trans-ventricular approach, four using the anterior trans-callosal approach and, three patients by using an endoscopic approach. In all patients, complete excision of the lesions was achieved. CONCLUSION: Colloid cysts, though benign, present surgical challenges because of its deep midline location. Complete excision of the colloid cyst carries an excellent prognosis. Surgery is a safe and effective treatment option for this benign lesion.

scholarly journals Comparison between SARS-CoV and SARS-CoV 2

2021 ◽  
Vol 271 ◽  
pp. 03022
Author(s):  
Meng Fang
Keyword(s):  
Transmission Rate ◽  
Clinical Manifestations ◽  
Respiratory Illness ◽  
Global Community ◽  
Global Epidemic ◽  
The Third ◽  
Biological Features ◽  
The Past ◽  
Transmission Mechanisms ◽  
Viral Respiratory

COVID-19, which is officially called SARS-CoV-2, is a newly emerging viral respiratory illness leading to a global epidemic, which causes concerns among the global community in November 2019. SARS-CoV-2 is considered as the third global coronavirus epidemic in the past 20 years after SARS-CoV in 2002 and MERS in 2012. SARS is a viral respiratory illness caused by coronavirus SARS-CoV which was first reported in Guangdong, China in 2002. SARS-CoV-2 and SARS-CoV share similar and different biological features, clinical manifestations, region distribution, transmission mechanisms, and clinical treatments. In this paper, differences and similarities between SARS-CoV-2 and SARS-CoV are analyzed to provide valuable information for further research. Through analysis, we found SARS-CoV-2 and SARSCoV share a lot of similarities, but also have differences in clinical manifestations, pathogenicity, transmission rate and treatments.

scholarly journals Functioning adrenocortical carcinoma causing virilisation: a case report

2020 ◽  
Vol 7 (2) ◽  
pp. 442
Author(s):  
Vivek Parameswara Sarma ◽  
Sunil S. Menon
Keyword(s):  
Case Report ◽  
Steroid Hormone ◽  
Abdominal Mass ◽  
Female Child ◽  
Young Female ◽  
Imaging Features ◽  
Adrenal Hyperplasia ◽  
Fourth Decade ◽  
Localized Disease ◽  
Uncommon Tumor

Adrenocortical carticnoma (ACC) is an uncommon tumor with an incidence of 1-2 cases/million/year. It has two peak incidences; the first one in the first decade and the second one in the fourth decade. Most patients present with features of steroid hormone excess or abdominal mass effects, but about 15% of ACC are diagnosed incidentally. It is hormonally functional in 80 - 100% patients and the predisposing lesions include congenital adrenal hyperplasia and adenoma. ACC has significant syndromic and genetic association. Surgery offers the best chance of cure, especially in localized disease. Here, we present the case of virilization in a young female child secondary to a functioning ACC. The child had classical hormonal and imaging features of functioning ACC and underwent resection of the tumor (Adrenalectomy) with good outcome.

scholarly journals Ten-year evaluation of a Neonatal Screening Program for Congenital Adrenal Hyperplasia

2014 ◽  
Vol 58 (7) ◽  
pp. 765-771 ◽  
Author(s):  
Marilza Leal Nascimento ◽  
Anísia Nhelety Baptista Cristiano ◽  
Tatiane de Campos ◽  
Masanao Ohira ◽  
Edson Cechinel ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neonatal Screening ◽  
Screening Program ◽  
Clinical Manifestations ◽  
The State ◽  
Adrenal Hyperplasia ◽  
Santa Catarina ◽  
Salt Wasting ◽  
Neonatal Screening Program ◽  
Treatment Onset

Objective Evaluate the Neonatal Screening Program (NSP) for congenital adrenal hyperplasia (CAH) of the Department of Health of the State of Santa Catarina (Secretaria de Estado da Saúde de Santa Catarina, SES/SC), and provide information to improve the program. Subjects and methods Descriptive, retrospective study of 748,395 children screened between January 2001 and December 2010. We analyzed the coverage of the NSP-SES/SC prevalence of CAH, child’s age when the first sample for 17-hydroxyprogesterone (17OHP) measurement was collected, levels of 17OHP, mean age at treatment onset and main clinical manifestations. Results The NSP-SES/SC covered 89% of the live newborns in the State. It diagnosed 50 cases of CAH, yielding an incidence of 1:14,967. Mean age at collection of the first sample was 7.3 days and mean level of 17OHP was 152.9 ng/mL. The most frequent manifestations were virilized genitalia with nonpalpable gonads, clitoromegaly and genital hyperpigmentation. In three girls, the genre established at birth was incorrect. The salt-wasting form was present in 74% of the cases. There was no occurrence of shock or death. Mean age at treatment onset in the salt-wasting form was 17.4 days compared with 54.9 days in those without the salt-wasting form of the disease. All children were treated with hydrocortisone, and those with salt-wasting CAH were also treated with fludrocortisone. Conclusions The incidence of CAH was 1 case to 14,967 live newborns. Collection of the first sample occurred outside the recommended time, resulting in delays in treatment onset.

scholarly journals Therapeutic Effect and Metabolic Mechanism of A Selenium-Polysaccharide from Ziyang Green Tea on Chronic Fatigue Syndrome

Polymers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1269 ◽  
Author(s):  
Changzhuan Shao ◽  
Jing Song ◽  
Shanguang Zhao ◽  
Hongke Jiang ◽  
Baoping Wang ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Green Tea ◽  
Metabolic Pathways ◽  
Steroid Hormone ◽  
Chronic Fatigue ◽  
Gas Chromatography Mass Spectrometry ◽  
Urine Metabolites ◽  
Steroid Hormone Biosynthesis ◽  
Hormone Biosynthesis ◽  
Metabolic Mechanism

Ziyang green tea was considered a medicine food homology plant to improve chronic fatigue Ssyndrome (CFS) in China. The aim of this research was to study the therapeutic effect of selenium-polysaccharides (Se-TP) from Ziyang green tea on CFS and explore its metabolic mechanism. A CFS-rats model was established in the present research and Se-TP was administrated to evaluate the therapeutic effect on CFS. Some serum metabolites including blood urea nitrogen (BUN), blood lactate acid (BLA), corticosterone (CORT), and aldosterone (ALD) were checked. Urine metabolites were analyzed via gas chromatography-mass spectrometry (GC-MS). Multivariate statistical analysis was also used to check the data. The results selected biomarkers that were entered into the MetPA database to analyze their corresponding metabolic pathways. The results demonstrated that Se-TP markedly improved the level of BUN and CORT in CFS rats. A total of eight differential metabolites were detected in GC-MS analysis, which were benzoic acid, itaconic acid, glutaric acid, 4-acetamidobutyric acid, creatine, 2-hydroxy-3-isopropylbutanedioic acid, l-dopa, and 21-hydroxypregnenolone. These differential metabolites were entered into the MetPA database to search for the corresponding metabolic pathways and three related metabolic pathways were screened out. The first pathway was steroid hormone biosynthesis. The second was tyrosine metabolism, and the third was arginine-proline metabolism. The 21-hydroxypregnenolone level of rats in the CFS group markedly increased after the Se-TP administration. In conclusion, Se-TP treatments on CFS rats improved their condition. Its metabolic mechanism was closely related to that which regulates the steroid hormone biosynthesis.

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