Journal article
A. Admin, Weiwei Xu, L. Schiffer, Fahd Qadir, Yanqing Zhang, J. Hawley, Paula Mota De Sa, B. Keevil, Hongju Wu, W. Arlt, F. Mauvais-Jarvis
bioRxiv, 2020
bioRxiv, 2020
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APA
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Admin, A., Xu, W., Schiffer, L., Qadir, F., Zhang, Y., Hawley, J., … Mauvais-Jarvis, F. (2020). Intracrine testosterone activation in human pancreatic β cells stimulates insulin secretion. BioRxiv.
Chicago/Turabian
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Admin, A., Weiwei Xu, L. Schiffer, Fahd Qadir, Yanqing Zhang, J. Hawley, Paula Mota De Sa, et al. “Intracrine Testosterone Activation in Human Pancreatic β Cells Stimulates Insulin Secretion.” bioRxiv (2020).
MLA
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Admin, A., et al. “Intracrine Testosterone Activation in Human Pancreatic β Cells Stimulates Insulin Secretion.” BioRxiv, 2020.
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@article{a2020a,
title = {Intracrine testosterone activation in human pancreatic β cells stimulates insulin secretion.},
year = {2020},
journal = {bioRxiv},
author = {Admin, A. and Xu, Weiwei and Schiffer, L. and Qadir, Fahd and Zhang, Yanqing and Hawley, J. and Sa, Paula Mota De and Keevil, B. and Wu, Hongju and Arlt, W. and Mauvais-Jarvis, F.}
}
Abstract
Testosterone (T) affects β cell function in men and women. T is a pro-hormone that undergoes intracrine conversion in target tissues to the potent androgen dihydrotestosterone (DHT) via the enzyme 5α-reductase (5α-R), or to the active estrogen 17β-estradiol (E2) via the aromatase enzyme. Using male and female human pancreas sections, we show that the 5α-R type1 isoform (SRD5A1) and aromatase are expressed in male and female β cells. We show that cultured male and female human islets exposed to T produce DHT and downstream metabolites. In these islets, exposure to the 5α-R inhibitors finasteride and dutasteride inhibited T conversion into DHT. We did not detect T conversion into E2 from female islets. However, we detected T conversion into E2 in islets from one out of four male donors. In this donor, exposure to the aromatase inhibitor anastrozole inhibited E2 production. Notably, in cultured male and female islets, T enhanced glucose-stimulated insulin secretion (GSIS). In these islets, exposure to 5α-R inhibitors or the aromatase inhibitor both inhibited T enhancement of GSIS. In conclusion, male and female human islets convert T into DHT and E2 via the intracrine activities of SRD5A1 and aromatase. This process is necessary for T enhancement of GSIS.
