Cellular basis for the differential response of mouse kallikrein genes to hormonal induction.

Leeuwen, B. H. van; Penschow, Jennifer D.; Coghlan, John P.; Richards, Robert I.

doi:10.1002/j.1460-2075.1987.tb02421.x

Cited by 48 publications

(27 citation statements)

References 19 publications

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“…This strongly suggests (although it has not yet been confirmed by in situ hybridization analysis) that SMR1 is synthesized in the GCT cells of the SMG (like EGF, NGF, and renin and other androgen-regulated proteins in the SMG of mice). Moreover, the difference in the level of SMR1 mRNA accumulation in males and females (>3 orders of magnitude) is very high, as compared to that usually observed with other androgen-regulated genes in target organs (kidney, liver, SMG) (3,31). Due to the relative lack of cell replication during differentiation of the GCT cells (3), the SMG is a biological material much more convenient for the study transcriptional activation of genes by androgens than are secondary sex organs of the male genital tract (prostate, seminal vesicles); therefore, study of the regulation of SMR1 synthesis might be particularly useful for the understanding of the mechanism of action of androgens in target organs.…”

Section: Iolation and Sequence Of A Cdna Complementary To A Ratmentioning

confidence: 77%

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High level of accumulation of a mRNA coding for a precursor-like protein in the submaxillary gland of male rats.

Rosinski‐Chupin

Tronik

Rougeon

1988

Proc. Natl. Acad. Sci. U.S.A.

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NaDodSO4/PAGE analysis of in vitro translation products of rat submaxillary gland (SMG) mRNAs has revealed an important sexual dimorphism. Moreover, most of the rat male-specific major translation products differ in size from those translated from male mouse SMG mRNAs. To characterize proteins accumulated in the rat SMG under androgen control, a cDNA library was constructed. Here we report the nucleotide sequence of a 0.7-kilobase mRNA that is 1000-3000 times more abundant in male rats than in female rats. The predicted corresponding protein, SMR1, has a molecular weight of 16,000 and contains a signal peptide for secretion and potential signals for glycosylation. An interesting feature of SMR1 is the presence, in a hydrophilic region, of the tetrapeptide Gln-His-Asn-Pro surrounded by two pairs of basic residues that represent potential cleavage sites for maturation enzymes. In rats, the tissue distribution of the SMR1 mRNA is restricted to the SMG and the prostate. Only very low amounts of SMR1 mRNA can be detected in the SMG of male or female mice. Southern blot analysis indicates the presence of three genes in rats but only one in mice. Hypotheses on the physiological role of SMR1-derived peptides in male rats are discussed.A large number of polypeptides with biologically defined properties are synthesized at high levels in the submaxillary gland (SMG) of rodents (1) and particularly of mice. These proteins, including nerve growth factor (NGF), epidermal growth factor (EGF), and renin, share a number of properties. All are synthesized in the same cell type-the granular convoluted tubular (GCT) cells-in response to various hormonal stimuli, in particular to androgens (2). Further, these secretory proteins can be found in the saliva of mice and are synthesized as precursors that become active after posttranslational processing events, possibly involving kallikrein-like proteinases. Some of these kallikrein-like proteinases are also synthesized under androgen-control in the SMG (3).The biological significance of the accumulation of these polypeptides in the SMG of mice and of their release into the saliva is still unclear. Aggressive behavior in male mice results in the release into the blood of large amounts of submaxillary NGF and renin (4,5), providing some evidence that these molecules play a physiological role. But surprisingly, these proteins are not detected in the SMG of related species. For instance, renin, which represents 2% of the SMG proteins in wild-type and most inbred male mice (6) is not found in the SMG of rats (7). This suggests that these SMG-synthesized polypeptides could be related to the especially aggressive behavior of male mice.Attempts to characterize the genes regulated by androgens in the SMG of rats led us to analyze the patterns of in vitro translation products directed by the mRNAs of this tissue. As in mice, an important sexual dimorphism was observed in the rat SMG translation products. Moreover, the major polypeptides accumulated in the two species appeared to be very ...

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Section: Iolation and Sequence Of A Cdna Complementary To A Ratmentioning

confidence: 77%

“…Further, these secretory proteins can be found in the saliva of mice and are synthesized as precursors that become active after posttranslational processing events, possibly involving kallikrein-like proteinases. Some of these kallikrein-like proteinases are also synthesized under androgen-control in the SMG (3).…”

mentioning

confidence: 99%

High level of accumulation of a mRNA coding for a precursor-like protein in the submaxillary gland of male rats.

Rosinski‐Chupin

Tronik

Rougeon

1988

Proc. Natl. Acad. Sci. U.S.A.

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“…1986). whereas expression of other mouse kallikrein-like genes is predominantly in the testosteroneresponsive granular convoluted tubule cells of the male subman dibular gland (van Leeuwen et al, 1987). In other rodents, ex pression of kallikrein-like genes has also been detected in other testosterone-responsive secretory cells, including those of the prostate (Schachter, 1980) and testis (van Leeuwen et al, 1986).…”

Section: Discussionmentioning

confidence: 97%

Human prostate-specific antigen (APS) is a member of the glandular kallikrein gene family at 19q13

Sutherland

Baker

Hyland

et al. 1988

Cytogenet Genome Res

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The amino acid sequence of human prostate-specific antigen (APS) suggests that it is a member of the glandular kallikrein subfamily of serine proteases. In the mouse, the kallikrein-like family is localized in a single locus on chromosome 7, while other serine proteases are distributed over a variety of different chromosomes. To investigate the physical relationship between the human kallikrein genes, we have used in situ hybridization and Southern analysis of a human × mouse somatic cell hybrid panel to map the APS gene to 19q13, concordant with the renal kallikrein KLK 1 gene. This finding indicates that APS is a member of a human kallikrein-like gene family with analogous organization to that of the mouse.

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“…The kallikrein antibody showed crossreactivity with renallpancreatic kallikrein, the only glandular kallikrein synthesized in kidney (van Leeuwen et al, 1986) and striated and excretory duct cells of salivary glands (Penschow et al, 1991a;van Leeuwen et al, 1987). In the mouse kidney, kallikrein immunostaining was confined to the apical portion of cells of distal convoluted and connecting tubules.…”

Section: Immunocytochemistrymentioning

confidence: 94%

“…The mouse glandular kallikrein genes other than mGK-6 are expressed in the predominant population of granular convoluted tubule (GCT) cells of the SM (Penschow et al, 1991a,b;van Leeuwen et al, 1987). These cells also synthesize many other peptide hormones, including epidermal growth factor (EGF), nerve growth factor (NGF), and renin (Wilson et al, 1986;Rall et al, 1985;k a k a et al, 1981), all of which can be released into the circulation (Aloe et al, 1986;%utsumi et al, 1986;Menzie et al, 1974).…”

Section: Introductionmentioning

confidence: 99%

Secretion of glandular kallikrein and renin from the basolateral pole of mouse submandibular duct cells: an immunocytochemical study.

Penschow

Jp²

1993

J Histochem Cytochem.

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Glandular kallikrein from salivary glands in rats has been measured in the circulation and has been shown to have local vasoactive effects. In mice, renin and epidermal growth factor from the submandibular gland (SM) also reach the circulation, as both have been measured in plasma. The route by which these peptides enter the blood from their site of synthesis in ducts of the SM is unclear. We have investigated by immunocytochemistry the secretory pathways for kallikrein and renin from salivary duct cells in mice. The renal/pancreatic kallikrein-secreting cells of the striated and excretory ducts of the SM were distinguished from the granular convoluted tubule (GCT) cells which secrete other glandular kallikreins on the basis of data obtained in previous studies, in which we used gene-specific oligonucleotide probes to identify the expressing cell types. Renal/pancreatic kallikrein was apparently secreted constitutively from the basolateral surface of striated duct cells and in secretory vesicles from excretory duct cells, whereas apical secretion occurred via the regulated pathway in both cell types. Glandular kallikreins and renin synthesized in GCT cells were secreted from the basolateral surface by dissolution of granules at the cell membrane. There were fenestrated capillaries underlying the duct tree which would enable the secreted products to reach the circulation.

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Cellular basis for the differential response of mouse kallikrein genes to hormonal induction.

Cited by 48 publications

References 19 publications

High level of accumulation of a mRNA coding for a precursor-like protein in the submaxillary gland of male rats.

High level of accumulation of a mRNA coding for a precursor-like protein in the submaxillary gland of male rats.

Human prostate-specific antigen (APS) is a member of the glandular kallikrein gene family at 19q13

Secretion of glandular kallikrein and renin from the basolateral pole of mouse submandibular duct cells: an immunocytochemical study.

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