ABSTRACT
Beta-glucuronidase (GUS) is a lysosomal enzyme that, in mouse kidney, is subject to control by multiple hormones: androgen, which increases GUS transcription; estrogen, which antagonizes androgen-mediated stimulation of GUS; and growth hormone (GH), which appears to be necessary for the full androgen effect. Neither estrogen nor GH affects GUS in the absence of androgen. In hypophysectomized or pituitary dwarf mice the reduced androgen stimulation of GUS can be partially restored with GH treatment. Androgen-induced GUS mRNA increased significantly with intermittent GH, compared to no GH or continuous GH. Intact mice subjected to continuous infusion of GH showed a depressed androgen effect on GUS similar to that seen in GH-deficient mice. Thus, pulsatile GH is required for the full androgen response. Insulin-like growth factor-I (IGF-I) also restored GUS induction by androgen in GH-deficient mice. We conclude that GH enhances the effect of androgen on the GUS gene via IGF-I. Using transgenic mice, we have also identified a genetic variant of the GUS gene that is insensitive to GH enhancement of the androgen effect.
Subject(s)
Glucuronidase/genetics , Growth Hormone/pharmacology , Insulin-Like Growth Factor I/pharmacology , Kidney/enzymology , Animals , Dwarfism/enzymology , Female , Growth Hormone/administration & dosage , Growth Hormone/deficiency , Hypophysectomy , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Orchiectomy , Periodicity , RNA, Messenger/biosynthesis , Testosterone/pharmacologyABSTRACT
The hormone regulation of viruses has been of great interest since the discovery of glucocorticoid stimulation of mouse mammary tumor virus via a hormone response element in the viral long terminal repeat (LTR) promoter region. This report describes the investigation of the hormone responsiveness of bovine leukemia virus (BLV), an oncogenic retrovirus that infects dairy and beef cattle worldwide. It is a member of the human T cell leukemia (HTLV)/BLV group of retroviruses, which encode a protein, Tax, that is essential for regulating transcription of their own proviruses and for transforming host cells. We investigated the responsiveness of BLV to the hormones 17 beta-estradiol, progesterone, prolactin, insulin, and dexamethasone, a potent glucocorticoid. Only dexamethasone, in combination with insulin or insulin/prolactin, consistently stimulated BLV expression, as measured by reverse transcriptase activity, RNA blot hybridization (Northern blots), and CAT (chloramphenicol acetyltransferase) reporter assays of cell lines transiently or stably transfected with the BLV LTR. This effect required the presence of glucocorticoid receptors and Tax. This is the first report of hormone responsiveness in a virus of the HTLV/BLV group.
