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EMBO J. Dec 1, 1987; 6(12): 3711–3717.
PMCID: PMC553841

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

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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  • 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Cato AC, 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. [PMC free article] [PubMed]
  • Cato AC, 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. [PMC free article] [PubMed]
  • 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]
  • Chandler VL, Maler BA, Yamamoto KR. DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo. Cell. 1983 Jun;33(2):489–499. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Cunha GR, Chung LW, Shannon JM, Taguchi O, Fujii H. Hormone-induced morphogenesis and growth: role of mesenchymal-epithelial interactions. Recent Prog Horm Res. 1983;39:559–598. [PubMed]
  • Darbre P, Page M, King RJ. Androgen regulation by the long terminal repeat of mouse mammary tumor virus. Mol Cell Biol. 1986 Aug;6(8):2847–2854. [PMC free article] [PubMed]
  • Fawell SE, Pappin DJ, McDonald CJ, Higgins SJ. 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. [PubMed]
  • Frischauf AM, Lehrach H, Poustka A, Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. [PubMed]
  • Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13;320(6058):134–139. [PubMed]
  • Gubler U, Hoffman BJ. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. [PubMed]
  • Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. [PubMed]
  • Hanspal JS, Bushell GR, Ghosh P. Detection of protease inhibitors using substrate-containing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Anal Biochem. 1983 Jul 15;132(2):288–293. [PubMed]
  • von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. [PMC free article] [PubMed]
  • Heussen C, Dowdle EB. Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Anal Biochem. 1980 Feb;102(1):196–202. [PubMed]
  • Hurst HC, Parker MG. Rat prostatic steroid binding protein: DNA sequence and transcript maps of the two C3 genes. EMBO J. 1983;2(5):769–774. [PMC free article] [PubMed]
  • Hynes N, van Ooyen AJ, 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. [PMC free article] [PubMed]
  • Jensen EV, Suzuki T, Kawashima T, Stumpf WE, Jungblut PW, DeSombre ER. 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. [PMC free article] [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Laskowski M, Jr, Kato I. Protein inhibitors of proteinases. Annu Rev Biochem. 1980;49:593–626. [PubMed]
  • Lee DC, McKnight GS, Palmiter RD. 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]
  • Lehrach H, Diamond D, Wozney JM, Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. [PubMed]
  • Massot O, Baskevitch PP, 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. [PubMed]
  • Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, Green MR. 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. [PMC free article] [PubMed]
  • Mills JS, Needham M, Thompson TC, Parker MG. Androgen-regulated expression of secretory protein synthesis in mouse ventral prostate. Mol Cell Endocrinol. 1987 Sep;53(1-2):111–118. [PubMed]
  • Mills JS, Needham M, Parker MG. Androgen regulated expression of a spermine binding protein gene in mouse ventral prostate. Nucleic Acids Res. 1987 Oct 12;15(19):7709–7724. [PMC free article] [PubMed]
  • Pang SF, Chow PH, Wong TM. 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. [PubMed]
  • Parker MG. Mechanism of steroid hormone action. Cancer Surv. 1986;5(3):625–633. [PubMed]
  • Parker MG, Mainwaring WI. Effects of androgens on the complexity of poly(A) RNA from rat prostate. Cell. 1977 Oct;12(2):401–407. [PubMed]
  • Parker MG, Scrace GT, Mainwaring WI. Testosterone regulates the synthesis of major proteins in rat ventral prostate. Biochem J. 1978 Jan 15;170(1):115–121. [PMC free article] [PubMed]
  • Parker MG, 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]
  • Payvar F, DeFranco D, Firestone GL, Edgar B, Wrange O, Okret S, Gustafsson JA, Yamamoto KR. 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. [PubMed]
  • Ponta H, Kennedy N, Skroch P, Hynes NE, 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. [PMC free article] [PubMed]
  • Proudfoot NJ, Brownlee GG. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. [PubMed]
  • Rushmere NK, Parker MG, Davies P. Androgen receptor-binding regions of an androgen-responsive gene. Mol Cell Endocrinol. 1987 Jun;51(3):259–265. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Wilbur WJ, Lipman DJ. Rapid similarity searches of nucleic acid and protein data banks. Proc Natl Acad Sci U S A. 1983 Feb;80(3):726–730. [PMC free article] [PubMed]
  • Williams-Ashman HG. Regulatory features of seminal vesicle development and function. Curr Top Cell Regul. 1983;22:201–275. [PubMed]
  • Yamamoto KR. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. [PubMed]
  • 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. [PubMed]
  • Ziff EB, Evans RM. 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. [PubMed]

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