Testosterone regulates the synthesis of major proteins in rat ventral prostate

Parker, Malcolm G.; Scrace, Geoffrey T.; Mainwaring, W.I.P.

doi:10.1042/bj1700115

Cited by 136 publications

(52 citation statements)

References 32 publications

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“…C3 is one subunit of prostatic steroid-binding protein, which is a major protein accounting for 40% of the total proteins secreted by mature rat ventral prostate (Heyns and DeMoor, 1977;Parker et al, 1978). There is a good correlation between the onset of prostatic steroid-binding protein gene expression and androgen receptor concentration (Zhang et al, 1988).…”

Section: Expression Of Mrnamentioning

confidence: 99%

Effects of Perinatal Exposure to Flutamide on Sex Hormone Responsiveness in F1 Male Rats

Miyata

Yabushita

Sano³

et al. 2003

J. Toxicol. Sci.

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-Pregnant rats were administered flutamide (0 and 10 mg/kg, p.o.) from gestation Day 14 to post-parturition Day 3 and effects on responsiveness to androgens (testosterone propionate, TP; dihydrotestosterone, DHT) in male offspring were examined with a Hershberger assay.Male pups of each group were assigned to 6 subgroups as follows: Group 1, castration and euthanized at postnatal Day 46 (PND 46); Group 2, castration + vehicle; Group 3, castration + TP; Group 4, castration + DHT; Group 5, vehicle; Group 6, DHT. After castrations were conducted at PND 36, animals were treated with TP (2 mg/kg in corn oil, s.c.) or DHT (1.25 mg/kg in corn oil, s.c.) once a day for 10 days, beginning at PND 46. At PND 56, the following organs/tissues were removed and weighed: ventral prostate, dorso-lateral prostate, seminal vesicles with coagulating glands, levator ani muscle plus bulbocavernosus muscle, Cowper's gland, and glands penis. Analysis of serum testosterone, LH and FSH in Groups 2, 3, 4, 5 and 6, and RT-PCR using prostate tissue from Groups 2, 3 and 4 were carried out.Perinatal exposure to flutamide caused decreased weights of androgen-dependent organs. Responses to androgens were recognized in organs of all castrated groups, with increased organ weights, especially in animals administered TP where values were essentially equal to or greater than those of intact animals in both the control and the 10 mg/kg group. On the other hand, the degree of weight increase of the ventral prostate and seminal vesicles with TP or DHT treatment in castrated animals was smaller in the flutamide administration group than in the controls. In hormone assays, castrated + vehicle animals showed higher serum LH than the other groups. Serum FSH was high in the castrated groups (Group2>Group 4>Group3), while in the noncastrated group a constant level was noted, with or without flutamide. No effect of flutamide administration was observed regarding sex hormone. RT-PCR using ventral prostate tissue revealed no significant differences in expression of AR, C3, VEGF, TGF-beta1, beta2, KGF and CK8 mRNA after androgen treatment between the control and flutamide treatment groups. C3 mRNA was increased in androgen-treated animals, whereas AR, TGF-beta and KGF mRNAs were decreased.Perinatal exposure to anti-androgen causes irreversible abnormalities in male pups. Concerning the responsiveness to TP and DHT, the degrees of weight changes in ventral prostate and seminal vesicles in castrated animals were decreased. However, the other organ weights, the sex hormone levels and androgen-reactive gene expression in the ventral prostate were not influenced by perinatal flutamide treatment in the present study.

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Section: Expression Of Mrnamentioning

confidence: 99%

Effects of Perinatal Exposure to Flutamide on Sex Hormone Responsiveness in F1 Male Rats

Miyata

Yabushita

Sano³

et al. 2003

J. Toxicol. Sci.

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“…The protein is an oligomer containing Cl, C2, and C3 polypeptides (8) whose expression is stimulated markedly by testosterone (15). In common with other classes of steroid hormone (21), the mechanism whereby androgens regulate the expression of the steroid-binding protein is via effects on rates of gene transcription; in addition, androgens also modulate nuclear RNA turnover (13,22).…”

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confidence: 99%

Tissue-specific and hormonal regulation of the gene for rat prostatic steroid-binding protein in transgenic mice.

Allison¹,

Zhang²,

Parker³

1989

Mol. Cell. Biol.

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We investigated the tissue-specific and hormonal regulation of the gene for rat prostatic steroid-binding protein by introducing the C3(1) gene with 4-kilobase (kb) upstream and 2-kb downstream flanking sequences into transgenic mice. There was selective expression in the ventral prostate that was stimulated by testosterone, which indicated that the gene together with 6-kb flanking DNA contains the information required for prostate-specific and testosterone-regulated expression.

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“…Regulatory sequences for eucaryotic genes may be found in intervening sequences as well as in the 5'-noncoding region (1,3,12,30,34). Because the C3 gene is regulated in vivo by androgen (26), it is possible that androgen regulation of these transfected genes could be conferred by the intervening sequences in the C3 genomic clone rather than the MMTV LTR. To eliminate this possibility, a set of analogous transfections were carried out in S115 cells with a similar vector but with a cDNA sequence for human 3-interferon instead of the rat C3(1) gene (Fig.…”

Section: Resultsmentioning

confidence: 99%

Androgen regulation by the long terminal repeat of mouse mammary tumor virus.

Darbre¹,

Pagé²,

King³

1986

Mol. Cell. Biol.

130

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Mouse mammary tumor virus (MMTV) has long been implicated in mouse mammary carcinogenesis, and it is now well established that the long terminal repeat (LTR) contains regulatory sequences responsible for glucocorticoid-mediated induction of viral RNA. However, we have demonstrated previously that androgens as well as glucocorticoids can regulate MMTV RNA in the S115 mouse mammary tumor cell line. To determine if androgens act directly on the LTR in these cells, plasmids were constructed with the MMTV LTR joined to the coding sequences of genes not normally expressed in the cells. Following transfection of these chimeric genes into S115 cells, we show that the expression of the genes is regulated by both androgens and glucocorticoids. Furthermore, hormonal regulation is also conferred by the LTR on the neighboring guanine phosphoribosyltransferase (gpt) gene. Thus, androgens can act on the LTR of MMTV when the appropriate receptors are present in the cells, and this interaction can influence the expression of additional adjacent genes.Models of the mechanism of carcinogenesis by mouse mammary tumor virus (MMTV) stress the importance of the regulatory regions of the long terminal repeat (LTR) (10, 21), and this has been emphasised in recent reports on the biological effects of the MMTV LTR fused to oncogenes (17,22,25,31). In latter studies the glucocorticoid sensitivity of the MMTV LTR was used to substantiate the biological relevance of the results. It is well established that the glucocorticoid receptor binds to specific regions within the LTR (15), and these DNA sequences may show some enhancer-like properties (2).We have been studying the way in which steroids regulate cell growth and MMTV-related RNA in the S115 mouse mammary tumor cell line (4, 6, 7). Our data indicate that both androgens and glucocorticoids regulate MMTV RNA, whereas previous work showed that only glucocorticoids were active (35). This discrepancy could be explained on the basis that the MMTV LTR might respond to <0.01% ethanol in culture medium. Cells were subcultured at weekly intervals.Construction of transfection vectors. (i) Construction of LTR-C3-pSV2gpt. The 9-kilobase (kb) BamHI fragment containing the genomic rat C3(1) gene from the genomic clone X11B (28) was treated with Bal 31 nuclease to remove the 5' end of the gene up to position 6, and synthetic EcoRI linkers were added to the 5' end. This fragment was then cloned into the EcoRI-BamHI site of the vector pSV2gpt (19). The 1.4-kb PstI fragment of MMTV LTR (milk-borne strain from GR mice) (11) was cut with AvaI (position 62) and BstEII (position 1331). EcoRI linkers were put at both ends of the 1.269-kb fragment, which was then cloned into the EcoRI site of the vector (see Fig. 1A).(ii) Construction of LTR-interferon-pSV2gpt. Construction of LTR-interferon-pSV2gpt was similar to that described above, except that the inserted BamRI fragment was not of the rat C3(1) gene but of human ,B-interferon cDNA linked to the RNA termination signals of polyomavirus DNA (see Fig. 1B).(...

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Testosterone regulates the synthesis of major proteins in rat ventral prostate

Cited by 136 publications

References 32 publications

Effects of Perinatal Exposure to Flutamide on Sex Hormone Responsiveness in F1 Male Rats

Effects of Perinatal Exposure to Flutamide on Sex Hormone Responsiveness in F1 Male Rats

Tissue-specific and hormonal regulation of the gene for rat prostatic steroid-binding protein in transgenic mice.

Androgen regulation by the long terminal repeat of mouse mammary tumor virus.

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