Sertraline Suppresses Testis and Adrenal Steroid Production and Steroidogenic Gene Expression While Increasing LH in Plasma of Male Rats Resulting in Compensatory Hypogonadism

Toxicological Sciences : an Official Journal of the Society of Toxicology
Cecilie Hurup MunkboelBjarne Styrishave

Abstract

Selective serotonin reuptake inhibitors are used as first line treatment in major depressive disorder. However, selective serotonin reuptake inhibitors have also been associated with sexual disorders, abnormalities, and sexual dysfunction, although mechanisms are unclear. The aim of this project was to investigate the possible endocrine disrupting effect of sertraline (SER) on sex steroid production in male rats exposed to 3 therapeutically realistic doses of SER 1.25, 5, and 20 mg/kg/day. To achieve this, we analyzed all the major steroids in testis, adrenals, brain, and plasma using Liquid chromatography tandem mass spectrometry. Furthermore, we investigated the potential effects on gene expression on the major genes involved in testicular, adrenal and brain steroidogenesis using quantitative PCR. Moreover, plasma luteinizing hormone (LH) levels were analyzed. We observed significant reduction in steroid production, in particular on the testicular Δ-4 axis and on the adrenal CYP17-hydroxylase axis. Effects in brain and plasma were less pronounced. Testicular gene transcription was also significantly down-regulated except for the CYP19 (aromatase) gene. In contrast, no effects on the adrenal gene expression were observed, exce...Continue Reading

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Citations

Nov 28, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Giustino OrlandoLucia Recinella
Mar 27, 2018·Archives of Toxicology·Cecilie Hurup MunkboelBjarne Styrishave
Mar 8, 2021·European Journal of Pharmacology·Pavlina PavlidiChristina Dalla
Nov 8, 2019·European Journal of Pharmacology·Mayara Samala BezerraEdilson Dantas da Silva Junior

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