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...

hrp0089fc7.4 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2018

Altered Substrate Specificities and Metabolite Production by Aromatase (CYP19A1) Due to the R192H Mutation

Udhane Sameer S , Dick Bernhard , Pandey Amit V

Background: Aromatase (CYP19A1) a member of cytochrome P450 protein family is a major steroid metabolizing enzyme which converts androgens to estrogens. Mutations in aromatase can lead to autosomal recessive aromatase deficiency. An R192H mutation in CYP19A1 described earlier caused severe phenotype of aromatase deficiency with regressive virilization of the 46,XX new-born, but without signs of androgen excess during pregnancy. Computational studies suggested that R192H disrup...

hrp0089fc14.3 | Multisystem Endocrine Disorders | ESPE2018

Regulation of Salt, Sugar and Sex Steroids in Humans by Genetic Variations in NADPH Cytochrome P450 Oxidoreductase (POR) Identified in 1000 Genome Samples

Pandey Av Amit V , Udhane Sameer S , Parween Shaheena

A broad spectrum of human diseases, including abnormalities in steroidogenesis, are caused by mutations in the NADPH cytochrome P450 oxidoreductase (POR) (1-4). Human POR is a diflavin reductase that transfers electrons from NADPH to small molecules, non-P450 redox partners and cytochrome P450 proteins in the endoplasmic reticulum. Cytochrome P450 proteins perform a very wide range of reactions, including metabolism of steroids, drugs and other xenobiotics. Therefore, genetic ...

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 ...

hrp0089p2-p343 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology P2 | ESPE2018

Clinical, Biochemical, Structural and Functional Characterization of a Novel P450 Oxidoreductase Mutation Causing Virilization in a 46,XX Patient

Camats Nuria , Benito-Sanz Sara , Parween Shaheena , Lopez-Siguero Juan-Pedro , Fernandez-Cancio Monica , Fluck Christa E , Udhane Sameer S , Kagawa Norio , Audi Laura , Pandey Amit V

Background: Cytochrome P450 oxidoreductase (POR) deficiency (PORD) is a form of congenital adrenal hyperplasia (CAH) and results in steroid-production loss from cytochrome P450 proteins. Mutations in POR cause mild to severe forms of CAH with/without bone malformation symptoms resembling Antley-Bixler syndrome. We report a novel POR Arg550Trp mutation identified in a 46,XX patient with signs of aromatase (ARO) deficiency. Child (first pregnancy) and mother pr...