Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Testosterone-induced persistent dysregulations and transdifferentiation to exocrine pancreas in the female liver


ABSTRACT: 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 – 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 – once induced – 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.

ORGANISM(S): Mus musculus

SUBMITTER: Denis Delic 

PROVIDER: E-GEOD-13388 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

altmetric image

Publications

Testosterone-induced upregulation of miRNAs in the female mouse liver.

Delić Denis D   Grosser Christian C   Dkhil Mohamed M   Al-Quraishy Saleh S   Wunderlich Frank F  

Steroids 20100701 12


Testosterone (T) regulates expression of protein-encoding genes directly through androgen receptor (AR) targeting androgen response element (ARE) in gene promoters or indirectly through non-genotropic mechanisms, but only limited information is available about T effects on expression of gene-regulatory non-coding miRNAs. Here, we investigate the effect of T on miRNA expression profiles in the female mouse liver using miRXplore microarrays and quantitative RT-PCR. T treatment for 3 weeks induced  ...[more]

Similar Datasets

2009-10-28 | GSE13388 | GEO
2003-05-28 | GSE438 | GEO
2011-09-29 | E-GEOD-29768 | biostudies-arrayexpress
2008-06-13 | E-GEOD-438 | biostudies-arrayexpress
2009-09-30 | GSE15243 | GEO
2009-10-10 | E-GEOD-15243 | biostudies-arrayexpress
2008-04-04 | E-GEOD-10911 | biostudies-arrayexpress
2020-12-31 | GSE149406 | GEO
2023-12-28 | GSE235867 | GEO
2015-01-08 | GSE62696 | GEO