Effects of dihydrotestosterone on gene expression in mammary gland

Abstract

Breast cancer is the most common cancer among women. Androgens, the male sexual hormones produced by ovary, act as protector of mammary gland. To elucidate the possible effects of dihydrotestosterone (DHT) on the transcriptome of mammary gland, serial analysis of gene expression was carried out on three groups of gonadectomized mice. After gonadectomy (GDX), DHT was injected 3 or 24 h before sacrifice, whereas the control (GDX) group received vehicle solution. Approximately 42,000 tags were sequenced in each group. Genes involved in the cytoskeletal and extracellular matrix, such as troponin I skeletal fast 2 and keratin complex 1 acidic gene 14, were upregulated. In the immunity, complement component 1 q subcomponent gamma polypeptide and expressed sequence tag similar to lectin galactose binding soluble 3 were downregulated by DHT, whereas serine (or cystein) proteinase inhibitor clade A member 1a was upregulated. In the energy metabolism, the gene expression level of cytochrome c oxidase subunit I was upregulated by DHT, while NADH dehydrogenase subunit 2 was downregulated. In addition, transcripts involved in transport metabolism, such as apolipoprotein A-1, were upregulated by DHT, whereas retinol binding protein 4 plasma was downregulated. Several previously unknown sequence tags were identified, which may allow to characterize new molecules of interest. These results suggest the suppression of immune response in normal mammary gland after DHT injection. This study can assist in refining research on the role of androgens in mammary gland homeostasis and breast cancer.