hrp0095p1-208 | Adrenals and HPA Axis | ESPE2022

Targeting melanocortin type 2 receptor (MC2R) with peptides for the treatment of congenital adrenal hyperplasia

V Pandey Amit , Singh Shripriya , Parween Shaheena

Congenital adrenal hyperplasia (CAH) is a common disorder of steroid production mainly caused by a mutated CYP21A2 gene, causing 21-hydroxylase deficiency (21OHD). CAH due to 21OHD requires lifelong mineralocorticoid (MC) and glucocorticoid (GC) therapy. But, from the location of the enzyme block in the steroid production and increase of adrenocorticotropic hormone (ACTH) which stimulates the melanocortin type 2 receptor (MC2R) in the adrenal, excessive adrenal androgen produc...

hrp0098rfc9.3 | Sex Endocrinology and Gonads | ESPE2024

Nanoencapsulated Curcumin-Piperine Complex: A Breakthrough in Targeting CYP17A1 for Managing Androgen Excess in Adolescents with PCOS.

Yakubu Jibira , Tagit Oya , Natsaridis Evangelos , du Toit Therina , V. Pandey Amit

Androgens play a pivotal role in the pathophysiology of Polycystic Ovary Syndrome (PCOS), a common endocrine disorder affecting adolescent girls. Elevated androgen levels are implicated in the development and progression of PCOS, leading to symptoms such as hirsutism, acne, and irregular menstrual cycles. In patients with PCOS, the inhibition of androgen synthesis presents a therapeutic challenge. Given its crucial role in androgen production, CYP17A1 has become a major target...

hrp0097p1-280 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2023

The Metabolism of 11-Oxy Androgens by Fetal CYP3A7 and CYP3A4 is Less Efficient Compared to Classical Androgens

du Toit Therina , E Flück Christa , V Pandey Amit , Groessl Michael

Steroidogenic enzyme expression in the fetal adrenal and the placenta hints at the production and metabolism of adrenal-derived 11-oxy androgens (11OxyAs) in the fetal-placental unit. Thus, 11OxyAs are present in placental tissue, fetal cord blood and neonatal serum, and could have a particular role during fetal development. The metabolism of the 11OxyAs in the fetal unit, therefore, presents as a focal point of investigation. Adrenal androgens are primarily metabolized by the...

hrp0098fc8.3 | Adrenals and HPA Axis 2 | ESPE2024

Insight into the role of TXNRD2 in steroidogenesis through a novel homozygous TXNRD2 splice variant

Brachet Cecile , Laemmle Alexander , Cools Martine , Sauter Kay-Sara , De Baere Elfride , Vanlander Arnaud , V. Pandey Amit , du Toit Therina , D. Voegel Clarissa , Heinrichs Claudine , Verdin Hannah , E. Flück Christa

Objective: Adrenal cortisol production occurs through a biosynthetic pathway which depends on NADH and NADPH for energy supply. The mitochondrial respiratory chain and the reactive oxygen species (ROS) detoxification system are therefore important for steroidogenesis. Mitochondrial dysfunction leading to oxidative stress has been implicated in the pathogenesis of several adrenal conditions. Nonetheless, only very few patients with variants in one gene of the R...

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 ...

hrp0095fc3.3 | Early Life and Multisystem Endocrinology | ESPE2022

Targeting androgen production by post-translational regulation of CYP17A1 lyase activity

Sharma Katyayani , Pandey Amit V

Introduction: Over-production of androgens is linked to prostate cancer (PCa) in men and polycystic ovary syndrome (PCOS) in women. CYP17A1 produces dehydroepiandrosterone (DHEA), the precursor for androgens, via its 17,20 lyase activity. CYP17A1 lyase activity is regulated by the amount of P450 reductase for electron transfer; the presence of cytochrome b5; and protein phosphorylation. High androgen levels were linked to the phosphorylation of CYP17A1 protein...

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...

hrp0095fc3.4 | Early Life and Multisystem Endocrinology | ESPE2022

A common polymorphism in the human P450 reductase gene (POR) causes defective steroid and drug metabolism due to protein instability

Rojas Velazquez Maria Natalia , Noebauer Mathias , Pandey Amit V

Cytochrome P450 oxidoreductase (POR) is the obligatory redox partner of steroid and drug-metabolizing cytochrome P450s located in the endoplasmic reticulum. Mutations in POR cause a broad range of disorders like congenital adrenal hyperplasia that may resemble bone malformations resembling Antley-Bixler syndrome. Genome sequencing studies have revealed the existence of a POR missense variant P228. We aimed to determine the detailed functional impact of POR variant P228L for it...