hrp0089fc5.3 | Thyroid | ESPE2018

Computational Analysis of the Ligand Binding Domain of the Thyroid Hormone Receptor for the Rational Design of an Efficient Protein-Based Biosensor for the Detection of Thyroid Hormone Disrupting Chemicals

Verma Sonia , Pandey Amit V

Background: Thyroid hormone disrupting chemicals (THDCs) which are present in the environment, food and everyday consumer products, interfere with thyroid hormone signaling, possibly by interacting with thyroid hormone receptors (THRs). This alters the thyroid hormone homeostasis and affects various functions regulated by the thyroid hormone e.g. macronutrient metabolism, cardiovascular function, and normal brain development. Therefore, there is a necessity for detection and m...

hrp0089rfc4.2 | GH & IGFs | ESPE2018

Data Mining and Computational Analysis of Human Growth Hormone Gene (GH1) Sequence in Normal Population to Identify Potential Variants with Disease-Causing Effects

Verma Sonia , Pandey Amit V

Background: Mutations in GH1 gene cause isolated growth hormone deficiency. Several disease-causing mutations from patients with IGHD have been reported. These mutations have been shown to (a) produce shorter isoforms of GH that does not bind to growth hormone receptor, (b) cause diminished secretion of GH or (c) result in misfolded GH protein. Large sequencing studies from the non-clinical population show several hundred genetic variations in GH1 gene. Role of common polymorp...

hrp0084p1-4 | Adrenal | ESPE2015

Effect of CYP17A1 Inhibitors Orteronel and Galeterone on Adrenal Androgen Biosynthesis

Udhane Sameer S , Pandey Amit V

Background: The cytochrome P450 CYP17A1 plays a vital role in regulating adrenal androgen production. The 17,20 lyase activity of CYP17A1 is key for androgen regulation. The orteronel and galeterone are known to inhibit 17,20 lyase activity however the detailed mechanisms of the inhibition of CYP17A1 activities remain unknown. These inhibitors have been developed to treat the castration resistant prostate cancer (CRPC) but little is known about their effects on adrenal androge...

hrp0092rfc13.6 | Adrenals and HP Axis | ESPE2019

Inhibitory Effects of Curcuminoids on the Enzymes from the Steroidogenic Pathway

Rodríguez Castaño Patricia , Pandey Amit V

Background: Turmeric is a popular ingredient in the cuisine of many Asian countries. It is also known for its use in Chinese and Ayurvedic medicine. It comes from the root of the Curcuma longa. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcumin has potent anti-inflammatory and anti-carcinogenic activities. Since many anti-cancer drugs target enzymes from the steroidogenic pathway, we tested the bioactivi...

hrp0092rfc15.3 | Late Breaking Abstracts | ESPE2019

Metformin Treatment Affects ACTH Receptor Activation and Downstream Signaling: A Potential Treatment for ACTH Excess Disorders and Management of Hyperandrogenic States

Parween Shaheena , Pandey Amit V. , Flueck Christa E.

Background: The peptide hormone adrenocorticotropin (ACTH or Corticotropin) is a major component of the stress response system in the Hypothalamus-Pituitary-Adrenal (HPA) axis. Under stress, it is secreted from the anterior pituitary and stimulates cortisol production from the adrenal cortex. Changes in ACTH production or action are associated with multiple disease conditions. In clinical situations like Cushing's disease, ectopic ACTH syndrome and congeni...

hrp0089fc1.3 | Adrenals & HPA Axis | ESPE2018

Targetting the Binding of ACTH to the Melanocortin Receptor by Structure Modeling and Design of Peptide antagonists to Block Excess Androgens in 21-hydroxylase Deficiency

Parween Shaheena , Fluck Christa E , Pandey Amit V

Background: The adrenocorticotropic hormone (ACTH) is a 39 amino acid polypeptide secreted by the anterior pituitary and regulates cortisol secretion from the adrenal cortex. Cortisol has negative feedback and regulates the synthesis and secretion of the ACTH. Excess ACTH is associated with a wide range of diseases including congenital adrenal hyperplasia (CAH). Classic CAH due to the 21-hydroxylase (CYP21A2) deficiency causes a reduction or loss of cortisol synthesis. Here th...

hrp0089rfc1.2 | Adrenals & HPA Axis | ESPE2018

Changes in CYP19A1 and CYP3A4 Activities due to Population Genetic Variations in Human P450 Oxidoreductase

Parween Shaheena , Udhane Sameer S , Kagawa Norio , Pandey Amit V

Background: Cytochromes P450 proteins metabolize several steroid hormones, drugs and xenobiotics. All cytochromes P450s in the endoplasmic reticulum require P450 oxidoreductase (POR) for their catalytic activities. Earlier it has been shown that mutations in POR cause metabolic disorders of steroid hormone biosynthesis and also affect some drug metabolizing P450 activities. We aimed to characterize the mutations identified in nonclinical samples to access their effects on ster...

hrp0086p1-p362 | Gonads & DSD P1 | ESPE2016

Aromatase Activity is Disrupted by Mutations in P450 Oxidoreductase

Udhane Sameer S. , Parween Shaheena , Pandey Amit V.

Background: The steroidogenic enzyme aromatase (CYP19A1) is a protein located in endoplasmic reticulum (ER) that catalyzes the conversion of androgens to estrogens. Both deficiency and excess of aromatase activity lead to disease states implicating its role in human biology. Cytochrome P450 (CYP) enzymes in ER use reduced nicotinamide adenine dinucleotide phosphate through cytochrome P450 oxidoreductase (POR) for their metabolic activities. Mutations in POR cause disorders of ...

hrp0084fc10.4 | Perinatal Endocrinology | ESPE2015

Effect of P450 Oxidoreductase Variants on Metabolism by Cytochrome P450 Proteins

Parween Shaheena , Udhane Sameer S , Pandey Amit V

Background: A broad spectrum of human diseases including abnormalities in steroidogenesis is caused by mutations in the NADPH P450 oxidoreductase (POR). POR transfers electrons from NADPH to several small molecules, non-P450 redox partners and all microsomal cytochrome P450 proteins. POR disruption affects all partners with disastrous consequences and POR knock-out mice are embryonically lethal. A number of POR mutations and polymorphisms have been characterized from patients ...

hrp0092fc3.3 | Multi-system Endocrine Disorders | ESPE2019

Variability in Drug Metabolizing Cytochrome P450 Activities Caused by Human Genetic Variations in NADPH Cytochrome P450 Oxidoreductase (POR)

Velazquez Maria Natalia Rojas , Parween Shaheena , Pandey Amit V

Background: A broad spectrum of human diseases, including abnormalities in steroidogenesis, are caused by mutations in the NADPH cytochrome P450 oxidoreductase (POR) (1-2). Cytochrome P450 proteins perform several reactions, including metabolism of steroids, drugs and other xenobiotics. Therefore, genetic variations in POR can impact many different metabolic pathways by changing the activities of cytochromes P450 (1). In 2004 the first human patients with defe...