Effect of 11BHSD inhibition on 11-ketotestosterone biosynthesis

The figures 2, 3, 4 and 6 in the main text of the manuscript: "Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 drives concurrent 11-oxygenated androgen excess", submitted to FASEB by Lina Schiffer, Imken Oestlund, Jacky Snoep, Lorna C. Gilligan, Angela E. Taylor, Alexandra J. Sinclair, Rishi Singhal, Adrian Freeman, Ramzi Ajjan, Ana Tiganescu, Wiebke Arlt and Karl-Heinz Storbeck, are reproduced in Mathematica notebooks. The notebooks and the corresponding Excel files with data are made available in the Investigation.

DOI: 10.15490/fairdomhub.1.investigation.658.1

Zenodo URL: None

Created at: 17th Mar 2024 at 09:01

Contents

HSD11B1/AKR1C3 ratio experiments

HSD11B1 and AKR1C3 transfected cells were mixed at difefrent ratios and effects on cortisone conversion (Fig. 2B) and 11KT production (Fig. 2C) were measured and simulated.

Data for HSD11B1/AKR1C3 ratio experiment in Fig. 2

Excel file with metablite profiles after 24 h incubation with different ratios of 11HSDB1 and AKR1C3.

Ratio experiments

Metabolite profiles after 24h incubation with different ratios of HSD11B1 and AKR1C3 transfected HEK293 cells.

  • Ratio experiments.xlsx

Model analysis for HSD11B1/AKR1C3 ratio experiment

Model simulations for 24h incubations with different ratios of HSD11B1 andd AKR1C3 transfected HEK293 cells are given in Mathematica notebook format.

Model simulation of metabolite profiles after 24h incubation with different ratios of HSD11B1 and AKR1C3 transfected HEK293 cells.

Mathematica notebook with model simulation of metabolite profiles after 24h incubation with different ratios of HSD11B1 and AKR1C3 transfected HEK293 cells.

  • Faseb-main-figures-2.nb

CBX inhibition of HSD11B1 and effect on HSD11B1/AKR1C3 incubations

HSD11B1 was inhibited by CBX and the effect of the inhibition on Cortisone and 11KA4 conversion by HSD11B1/AKR1C3 incubations were measured.

Experimental data for HSD11B1/AKR1C3 incubation with CBX inhibition

HSD11B1 was inhibited by CBX and conversion of cortisone and 11KA4 by HSD11B1 and AKR1C3 was followed over time.

Data file for HSD11B1/AKR1C3 conversion with CBX inhibition

HSD11B1 was inhibited by CBX and the effect on the conversion of cortisone and 11KA4 in HSD11B1/AKR1C3 incubations was followed.

  • CBX inhibition HSD11B1.xlsx

Model simulations of HSD11B1/AKR1C3 incubation and cortisone and 11KA4 inversion during CBX inhibition

HSD11B1 was inhibitied by CBX and the effect of the inhibition on cortisone and 11KA4 conversion was simulated. The model was coded in Mathematica and the f=manuscript figures 3 A,B,C,D,E anbd F are presented in the notebook.

Model simulations of HSD11B1/AKR1C3 incubation with CBX inhibition

HSD11B1 was inhibited by CBX and the effect on cortisone and 11KA4 conversion was simulated. Model simulated in Mathematica, Figure 3 panels are presented.

  • Faseb-main-figures-3.nb

Computational analysis of combined HSD11B1/AKR1C3 ratios and HSD11B1 inhibition

Surface plots showing the computational analysis of combined HSD11B1/AKR1C3 ratios and HSD11B1 inhibition.

Model for computational analysis of HSD11B1/AKR1C3 ratio variation and HSD11B1 inhibition.

A mathematica notebook that simulates the combined effect of HSD11B1/AKR1C3 ratio variation and HSD11B1 inhibition.

Mathematica notebook for simulation of HSD11B1/AKR1C3 ratio variation and HSD11B1 inhibition.

Mathematica notebook for simulation of combined effect of HSD11B1/AKR1C3 ratio variation and HSD11B1 inhibition, surface plots are generated shown in Fig. 4 of the manuscript.

  • Faseb-main-figures-4.nb

Inhibition of HSD11B1 in adipose tissue

HSD11B1 was inhibited in human subcutaneous and omental adipose tissue, and the effect on oxygenated adrogen metabolism was studied.

Inhibition of HSD11B1 in adipose tissue

Excel file with experimental data for HSD11B1 inhibition in human subcutaneous and omental adipose tissue. Effect on 72h point for cortisone, and 11KA4 metabolism and respective products formed in absence or presence of AZD4017 inhibitor.

HSD11B1 inhibition in human adipose tissue

Excel spreadsheet with 72h time points for metabolism of cortisone or 11KA4 in human subcutaneous or omental adipose tissue in presence or absence of AZD4017 inhibitor.

  • Adipose Data.xlsx

Simulation of HSD11B1 inhibition in human adipose tissue

Model simulation of cortisone or 11KA4 metabolism in human subcutaneous and omental adipose tissue, and the effect of AZD4017 inhibition of HSD11B1.

Mathematica notebook for simulation of HSD11B1 inhibition in human adipose tissue.

HSD11B1 inhibition by AZD4017 and the effect on cortisone and 11KA4 metabolism was simulated in Mathematica. Figure 6 of the manuscript is reproduced in the notebook.

  • Faseb-main-figures-6.nb
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Citation
Snoep, J. (2024). Effect of 11BHSD inhibition on 11-ketotestosterone biosynthesis. FAIRDOMHub. https://doi.org/10.15490/FAIRDOMHUB.1.INVESTIGATION.658.1
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Created: 17th Mar 2024 at 09:01

Last updated: 17th Mar 2024 at 09:02

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