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The Transcriptional Response to Androgens of the Rat VCSA1 Gene Is Amplified by Both Binary and Graded Mechanisms

Unité de Génétique et Biochimie du Développement, Unité de Recherche Associée 1960 Centre National de la Recherche Scientifique, Institut Pasteur, 75724 Paris Cédex 15, France

Address all correspondence and requests for reprints to: Dr. Isabelle Rosinski-Chupin, Unité de Génétique et Biochimie du Développement, Unité de Recherche Assocíee 1960 Centre National de la Recherche Scientifique, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris cedex 15, France. E-mail: ichupin{at}pasteur.fr

In higher eukaryotes, gene expression can be highly modified in response to small variations of circulating hormonal inducers. To determine the mechanisms responsible for the 100- to 200-fold enhancement of expression of an androgen-regulated gene, VCSA1, in the acinar cells of rat submandibular glands during puberty, we performed a detailed analysis of VCSA1 expression at the single cell level. Using in situ detection of mature and primary VCSA1 transcripts, we show that VCSA1 expression is activated in only a small proportion of differentiated acinar cells in the presence of low levels of circulating androgens in prepubescent and in castrated males, as well as in females. During the time course of sexual maturation in males, we demonstrate an increase in the proportion of acinar cells expressing VCSA1 and an increase in VCSA1 heterogeneous nuclear RNA and mRNA content in the positive cell population. Finally, we show that changes in the methylation pattern of VCSA1 are correlated with VCSA1 transcriptional activation. These results demonstrate that androgens can, in physiological conditions, elicit both a binary and a graded response. They also provide evidence that the range of gene regulation may be expanded by a transcriptional repression in a majority of cells under basal conditions.

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