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. 1987 Dec 1;6(12):3711–3717. doi: 10.1002/j.1460-2075.1987.tb02705.x

A secretory protease inhibitor requires androgens for its expression in male sex accessory tissues but is expressed constitutively in pancreas.

J S Mills 1, M Needham 1, M G Parker 1
PMCID: PMC553841  PMID: 3428272

Abstract

A full length cDNA clone encoding a mouse prostatic secretory glycoprotein (p12) whose synthesis is dependent upon testicular androgens has been cloned and characterized. The predicted amino acid sequence of p12 shares extensive homology with several members of the Kazal family of secretory protease inhibitors, in particular the pancreatic secretory trypsin inhibitors. In agreement with sequence data, prostatic secretory p12, purified from mouse ventral prostate secretion, exhibits anti-trypsin activity. Steady-state levels of protease inhibitor mRNA in ventral prostate are reduced from approximately 0.06% in normal mice to undetectable after androgen withdrawal but are inducible within 4 h by re-administration of testosterone. Androgen-dependent expression of the secretory protease inhibitor mRNA was also observed in coagulating gland and seminal vesicle. In seminal vesicle, a tissue of different embryonic origin to the prostate, the kinetics of secretory protease inhibitor mRNA loss after castration are not as rapid as in the ventral prostate and coagulating gland. Low-level androgen independent expression was also observed in the pancreas. There appears to be a single gene for this secretory protease inhibitor and yet expression is markedly stimulated by testosterone in the sex accessory tissues and unaffected by this hormone in the pancreas.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blobel G., Dobberstein B. Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol. 1975 Dec;67(3):835–851. doi: 10.1083/jcb.67.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buetti E., Diggelmann H. Glucocorticoid regulation of mouse mammary tumor virus: identification of a short essential DNA region. EMBO J. 1983;2(8):1423–1429. doi: 10.1002/j.1460-2075.1983.tb01601.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cato A. C., Henderson D., Ponta H. The hormone response element of the mouse mammary tumour virus DNA mediates the progestin and androgen induction of transcription in the proviral long terminal repeat region. EMBO J. 1987 Feb;6(2):363–368. doi: 10.1002/j.1460-2075.1987.tb04763.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cato A. C., Miksicek R., Schütz G., Arnemann J., Beato M. The hormone regulatory element of mouse mammary tumour virus mediates progesterone induction. EMBO J. 1986 Sep;5(9):2237–2240. doi: 10.1002/j.1460-2075.1986.tb04490.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cechová D., Meloun B. Differences in the evolution of seminal plasma acrosin inhibitors and pancreatic secretory trypsin inhibitors. Hoppe Seylers Z Physiol Chem. 1979 Oct;360(10):1497–1500. [PubMed] [Google Scholar]
  6. Chandler V. L., Maler B. A., Yamamoto K. R. DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo. Cell. 1983 Jun;33(2):489–499. doi: 10.1016/0092-8674(83)90430-0. [DOI] [PubMed] [Google Scholar]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Cunha G. R., Chung L. W., Shannon J. M., Taguchi O., Fujii H. Hormone-induced morphogenesis and growth: role of mesenchymal-epithelial interactions. Recent Prog Horm Res. 1983;39:559–598. doi: 10.1016/b978-0-12-571139-5.50018-5. [DOI] [PubMed] [Google Scholar]
  9. Darbre P., Page M., King R. J. Androgen regulation by the long terminal repeat of mouse mammary tumor virus. Mol Cell Biol. 1986 Aug;6(8):2847–2854. doi: 10.1128/mcb.6.8.2847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fawell S. E., Pappin D. J., McDonald C. J., Higgins S. J. Androgen-regulated proteins of rat seminal vesicle secretion constitute a structurally related family present in the copulatory plug. Mol Cell Endocrinol. 1986 May;45(2-3):205–213. doi: 10.1016/0303-7207(86)90149-8. [DOI] [PubMed] [Google Scholar]
  11. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  12. Green S., Walter P., Kumar V., Krust A., Bornert J. M., Argos P., Chambon P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13;320(6058):134–139. doi: 10.1038/320134a0. [DOI] [PubMed] [Google Scholar]
  13. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  14. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  15. Hanspal J. S., Bushell G. R., Ghosh P. Detection of protease inhibitors using substrate-containing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Anal Biochem. 1983 Jul 15;132(2):288–293. doi: 10.1016/0003-2697(83)90010-6. [DOI] [PubMed] [Google Scholar]
  16. Heussen C., Dowdle E. B. Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Anal Biochem. 1980 Feb;102(1):196–202. doi: 10.1016/0003-2697(80)90338-3. [DOI] [PubMed] [Google Scholar]
  17. Hurst H. C., Parker M. G. Rat prostatic steroid binding protein: DNA sequence and transcript maps of the two C3 genes. EMBO J. 1983;2(5):769–774. doi: 10.1002/j.1460-2075.1983.tb01498.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hynes N., van Ooyen A. J., Kennedy N., Herrlich P., Ponta H., Groner B. Subfragments of the large terminal repeat cause glucocorticoid-responsive expression of mouse mammary tumor virus and of an adjacent gene. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3637–3641. doi: 10.1073/pnas.80.12.3637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jensen E. V., Suzuki T., Kawashima T., Stumpf W. E., Jungblut P. W., DeSombre E. R. A two-step mechanism for the interaction of estradiol with rat uterus. Proc Natl Acad Sci U S A. 1968 Feb;59(2):632–638. doi: 10.1073/pnas.59.2.632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  21. Laskowski M., Jr, Kato I. Protein inhibitors of proteinases. Annu Rev Biochem. 1980;49:593–626. doi: 10.1146/annurev.bi.49.070180.003113. [DOI] [PubMed] [Google Scholar]
  22. Lee D. C., McKnight G. S., Palmiter R. D. The action of estrogen and progesterone on the expression of the transferrin gene. A comparison of the response in chick liver and oviduct. J Biol Chem. 1978 May 25;253(10):3494–3503. [PubMed] [Google Scholar]
  23. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  24. Massot O., Baskevitch P. P., Capony F., Garcia M., Rochefort H. Estradiol increases the production of alpha 1-antichymotrypsin in MCF7 and T47D human breast cancer cell lines. Mol Cell Endocrinol. 1985 Oct;42(3):207–214. doi: 10.1016/0303-7207(85)90050-4. [DOI] [PubMed] [Google Scholar]
  25. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mills J. S., Needham M., Parker M. G. Androgen regulated expression of a spermine binding protein gene in mouse ventral prostate. Nucleic Acids Res. 1987 Oct 12;15(19):7709–7724. doi: 10.1093/nar/15.19.7709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mills J. S., Needham M., Thompson T. C., Parker M. G. Androgen-regulated expression of secretory protein synthesis in mouse ventral prostate. Mol Cell Endocrinol. 1987 Sep;53(1-2):111–118. doi: 10.1016/0303-7207(87)90197-3. [DOI] [PubMed] [Google Scholar]
  28. Pang S. F., Chow P. H., Wong T. M. The role of the seminal vesicles, coagulating glands and prostate glands on the fertility and fecundity of mice. J Reprod Fertil. 1979 May;56(1):129–132. doi: 10.1530/jrf.0.0560129. [DOI] [PubMed] [Google Scholar]
  29. Parker M. G., Mainwaring W. I. Effects of androgens on the complexity of poly(A) RNA from rat prostate. Cell. 1977 Oct;12(2):401–407. doi: 10.1016/0092-8674(77)90116-7. [DOI] [PubMed] [Google Scholar]
  30. Parker M. G. Mechanism of steroid hormone action. Cancer Surv. 1986;5(3):625–633. [PubMed] [Google Scholar]
  31. Parker M. G., Scrace G. T., Mainwaring W. I. Testosterone regulates the synthesis of major proteins in rat ventral prostate. Biochem J. 1978 Jan 15;170(1):115–121. doi: 10.1042/bj1700115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Parker M. G., White R., Hurst H., Needham M., Tilly R. Prostatic steroid-binding protein. Isolation and characterization of C3 genes. J Biol Chem. 1983 Jan 10;258(1):12–15. [PubMed] [Google Scholar]
  33. Payvar F., DeFranco D., Firestone G. L., Edgar B., Wrange O., Okret S., Gustafsson J. A., Yamamoto K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983 Dec;35(2 Pt 1):381–392. doi: 10.1016/0092-8674(83)90171-x. [DOI] [PubMed] [Google Scholar]
  34. Ponta H., Kennedy N., Skroch P., Hynes N. E., Groner B. Hormonal response region in the mouse mammary tumor virus long terminal repeat can be dissociated from the proviral promoter and has enhancer properties. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1020–1024. doi: 10.1073/pnas.82.4.1020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Proudfoot N. J., Brownlee G. G. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. doi: 10.1038/263211a0. [DOI] [PubMed] [Google Scholar]
  36. Rushmere N. K., Parker M. G., Davies P. Androgen receptor-binding regions of an androgen-responsive gene. Mol Cell Endocrinol. 1987 Jun;51(3):259–265. doi: 10.1016/0303-7207(87)90036-0. [DOI] [PubMed] [Google Scholar]
  37. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Scheidereit C., Beato M. Contacts between hormone receptor and DNA double helix within a glucocorticoid regulatory element of mouse mammary tumor virus. Proc Natl Acad Sci U S A. 1984 May;81(10):3029–3033. doi: 10.1073/pnas.81.10.3029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  41. Wilbur W. J., Lipman D. J. Rapid similarity searches of nucleic acid and protein data banks. Proc Natl Acad Sci U S A. 1983 Feb;80(3):726–730. doi: 10.1073/pnas.80.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Williams-Ashman H. G. Regulatory features of seminal vesicle development and function. Curr Top Cell Regul. 1983;22:201–275. doi: 10.1016/b978-0-12-152822-5.50011-7. [DOI] [PubMed] [Google Scholar]
  43. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  44. Yamamoto T., Nakamura Y., Nishide J., Emi M., Ogawa M., Mori T., Matsubara K. Molecular cloning and nucleotide sequence of human pancreatic secretory trypsin inhibitor (PSTI) cDNA. Biochem Biophys Res Commun. 1985 Oct 30;132(2):605–612. doi: 10.1016/0006-291x(85)91176-3. [DOI] [PubMed] [Google Scholar]
  45. Ziff E. B., Evans R. M. Coincidence of the promoter and capped 5' terminus of RNA from the adenovirus 2 major late transcription unit. Cell. 1978 Dec;15(4):1463–1475. doi: 10.1016/0092-8674(78)90070-3. [DOI] [PubMed] [Google Scholar]
  46. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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