Androgen regulation of gene expression in primary epithelial cells of the mouse kidney.

Abstract

In proximal tubule cells of the mouse kidney, transcription of a number of genes is induced by androgens. Although a great deal of molecular and genetic information on the induction process has accumulated, the lack of an appropriate cell culture system for DNA transfection studies has hampered efforts to identify and characterize in detail the molecular factors that mediate the response. In the present paper, we have examined a primary renal epithelial cell culture system. We show that in response to androgens, these cells undergo induction of five messenger RNAs that are induced in the intact kidney; thus, the effects of androgens on renal gene expression derive from a direct action of the hormone on proximal tubule cells. The response does not occur in cells from Tfm animals, indicating that androgen receptor is required. Differences in patterns of androgen-inducible messenger RNA expression between mouse species are reflected by similar differences in the cultured cells. Interestingly, the kinetics of induction in culture seem to be distinct from those in the intact kidney, suggesting that a factor or factors differing between the whole animal and tissue culture environments influence the response. Transient transfection experiments with the primary cells showed that the 5'-flanking region of the androgen-regulated RP2 gene, which includes nucleotides -1500 to +42 and contains a glucocorticoid response element that binds the androgen receptor, does not mediate androgen-responsive transcription; thus, this region, and the glucocorticoid response element within it, are either insufficient for, or are not involved in, the gene's response to hormone.

Cloning and characterization of TDD5, an androgen target gene that is differentially repressed by testosterone and dihydrotestosterone

“…Almost all of these genes are expressed in the proximal tubule cells of the renal nephron. The expression of RP2, ODC, GUS, P450V, and ADH are induced by T and DHT (32). Due to their slow response, it does not surprise us that androgen-responsive elements identified cannot confer complete androgen responsiveness in reporter gene assays (31,32).…”

Kidney growth in 717 healthy children aged 0?18�months: a longitudinal cohort study

“…The volume measurements were log-transformed to obtain normally Gender difference tested with Mann-Whitney test. Level of significance *5%, **1%, and ***0.1% dependent increase in specific mRNAs [21]. In human kidney carcinoma cells, testosterone exerted a mitogenic effect by increasing protein and DNA synthesis [22].…”

The kidney is a major site of alpha(2)-antiplasmin production.

“…Kidneys from wild-type (C57/B6) and uPA-deficient mice (24) were flushed with 15 ml of serum-free defined medium (25,26). After dissection, kidneys were minced and cultured for 4 h in 2 ml of serum-free defined medium.…”