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Dissection of corticotroph transcriptome in a mouse model of glucocorticoid-induced suppression of the HPA axis

ABSTRACT: The effect on the transcriptome of dexamethasone (0.4mg/kg) treatment, and recovery 1 and 4 weeks following withdrawal was examined in corticotrophs FACS isolated from POMC-GFP mice. We show dexamethasone has persistent effects on the corticotroph transcriptome, some lasting up to 4 weeks.

ORGANISM(S): Mus musculus

PROVIDER: GSE165026 | GEO | 2022/01/03

REPOSITORIES: GEO

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Project description:Androgenic steroids are increasingly used for hormone therapy of postmenopausal women and abused as life style drugs and for doping purposes, though knowledge about associated health risks in females is very limited. In order to understand more about short- and long-term androgen effects on a molecular level, we have analyzed hepatic gene expression in female C57BL/6 mice immediately after subcutaneous treatment with testosterone for 3 weeks and after 12 weeks hormone withdrawal using Affymetrix array technology and quantitative real-time RT-PCR. Among about 14,000 genes examined, 48 were up- and 65 genes were downregulated by testosterone after 3-weeks treatment and about 50% of these changes persisted even 12 weeks after testostrone withdrawal. In addition to obvious risks such as induction of hepatocellular carcinomas and virilization of liver metabolism, testosterone induced a series of changes, as e.g. dysregulation of hepatic gene expression due to incomplete conversion of female to male phenotype â in particular downregulation of cytochrom P450 isoforms and sulfotransferases. As a long-term testosterone effect, transcripts emerged in the liver that are normally specific for the exocine pancreas including amylase 2, ribonuclease 1, and several trypsin-, chymotrypsin-, and elastase-like proteases. This transdifferentiation of hepatic to exocrine pancreatic tissue indicates that testosterone can initiate long-lasting differentiation programs, which â once induced â progress even after androgen withdrawal. This may have far-reaching consequences difficult to foresee implying long-term hazards of testosterone-treatment for female health that have not been taken into account yet. Mice were treated with testosterone or sesame oil (vehicle) for three weeks twice a week. Gene expression in the liver was analyzed either directly after treatment or after three weeks of hormone/vehicle withdrawal. For each of these four groups, three individual mice were used as biological replicates.

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Dissection of corticotroph transcriptome in a mouse model of glucocorticoid-induced suppression of the HPA axis

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