Submaxillary Gland Epidermal Growth Factor: A Sensitive Index of Biologic Androgen Activity

Barthe, P.; Bullock, Leslie P.; Mowszowicz, Irène; Bardin, C. Wayne; Orth, David N.

doi:10.1210/endo-95-4-1019

Cited by 87 publications

(34 citation statements)

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“…2). Considering the androgen dependence of the growth factor synthesis in the GCT (4,34) and that the PAP expression is under androgen regulation in the rat prostate (42), we can expect a similar androgen dependence in mouse SMG on the basis of the lack of tartrate-sensitive acid phosphatase activity in wild-type female saliva. At present, we know that PAP Ϫ/Ϫ mice display greater sensitivity in chronic inflammatory and neuropathic pain models mediated by adenosine (67).…”

Section: Discussionmentioning

confidence: 99%

Prostatic acid phosphatase is the main acid phosphatase with 5′-ectonucleotidase activity in the male mouse saliva and regulates salivation

Araujo

Quintero

Kipar

et al. 2014

American Journal of Physiology-Cell Physiology

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Araujo CL, Quintero IB, Kipar A, Herrala AM, Pulkka AE, Saarinen L, Hautaniemi S, Vihko P. Prostatic acid phosphatase is the main acid phosphatase with 5=-ectonucleotidase activity in the male mouse saliva and regulates salivation. Am J Physiol Cell Physiol 306: C1017-C1027, 2014. First published April 9, 2014; doi:10.1152/ajpcell.00062.2014.-We have previously shown that in addition to the well-known secreted isoform of prostatic acid phosphatase (sPAP), a transmembrane isoform exists (TMPAP) that interacts with snapin (a SNARE-associated protein) and regulates the endo-/exocytic pathways. We have also shown that PAP has 5=-ectonucleotidase and thiamine monophosphatase activity and elicits antinociceptive effects in mouse models of chronic inflammatory and neuropathic pain. Therefore, to determine the physiological role of PAP in a typical exocrine organ, we studied the submandibular salivary gland (SMG) of PAP Ϫ/Ϫ and wild-type C57BL/6J mice by microarray analyses, microRNA sequencing, activity tests, immunohistochemistry, and biochemical and physiological analyses of saliva. We show that PAP is the main acid phosphatase in the wild-type male mouse saliva, accounting for 50% of the total acid phosphatase activity, and that it is expressed only in the granular convoluted tubules of the SMGs, where it is the only 5=-ectonucleotidase. The lack of PAP in male PAP Ϫ/Ϫ mice was associated with a significant increase in the salivation volume under secretagogue stimulation, overexpression of genes related to cell proliferation (Mki67, Aurkb, Birc5) and immune response (Irf7, Cxcl9, Ccl3, Fpr2), and upregulation of miR-146a in SMGs. An increased and sustained acinar cell proliferation was detected without signs of glandular hyperplasia. Our results indicate that in PAP Ϫ/Ϫ mice, SMG homeostasis is maintained by an innate immune response. Additionally, we suggest that in male mice, PAP via its 5=-ectonucleotidase activity and production of adenosine can elicit analgesic effects when animals lick their wounds. acid phosphatase; transmembrane prostatic acid phosphatase; 5=-ectonucleotidase activity; TMPase activity; submandibular salivary gland PROSTATIC ACID PHOSPHATASE (PAP, E.C. 3.1.3.2) is a tartratesensitive histidine acid phosphatase enzyme with two known isoforms, the secreted (sPAP) and the type-I transmembrane (TMPAP) isoform, originating from alternative splicing of the same gene (Acpp) (45). Both isoforms are widely expressed in human and mouse tissues. In humans, PAP is predominately expressed in the prostate gland. TMPAP contains an extracellular NH 2 -terminal catalytic domain and a cytosolic COOHterminal domain, carrying a tyrosine-based endosomal/lysosomal targeting motif (Yxx) (45). In addition, TMPAP is an integral membrane protein of cells and is located in the plasma and vesicular membranes, from where it cycles through the endocytic/exocytic pathway via endosomes, multivesicular endosomes, lysosomes, and exosomes (46). Unlike the activity of other acid phosphatases, such as those derived from erythroc...

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Section: Discussionmentioning

confidence: 99%

Prostatic acid phosphatase is the main acid phosphatase with 5′-ectonucleotidase activity in the male mouse saliva and regulates salivation

Araujo

Quintero

Kipar

et al. 2014

American Journal of Physiology-Cell Physiology

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“…A survey of six inbred strains of mice revealed statistically significant differences in both sexes in the concentrations and amounts of EGF in the submandibular glands as measured by a radioimmunoassay procedure (7,8). Furthermore, in each strain the concentration of EGF in the gland of males was 30-500 fold greater than that of female mice (Fig.…”

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confidence: 98%

“…Since EGF is androgen-dependent, and its level in the gland is a sensitive indicator of circulating androgens (8), the difference in EGF levels in the two strains could conceivably be caused by a difference in plasma androgens.…”

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Biologically Active Polypeptides in Mouse Submandibular Gland

Barka

1980

Acta Histochem. Cytochem

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“…GCT cells in mice submandibular glands (SMGs) are unique structures containing a lot of growth factors (EGF and NGF etc.) (1,8,15,17) and they are strongly influenced by male hormone administration (2,5,7,12,18), and are dramatically reduced by 481 Takai et al testectomy (11,14). Keratin (KLIM) proteins exist specifically in ductal epithelial cells of salivary glands (4,19,23,28), lectin binding of ductal system, which has specific linkage to sugar residues in mice SMGs, shows different distribution patterns, in either acinar or GCT cells (16,20,25).…”

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Immunohistochemical observations of epidermal growth factor, keratin proteins and lectin binding on effects of testosterone administration in duct-ligated submandibular glands of mice.

Takai

Tatemoto

Noda

et al. 1986

Acta Histochem. Cytochem

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Histologic and histochemical changes of epidermal growth factor (EGF), keratin-like immunoreactive materials (KLIM) and lectin bindings (PNA, SBA and DBA) were reported in duct-ligated submandibular glands (SMGs) of mice with varying treatments of testosterone and with castration or both. Testosterone treatment before duct ligation of SMGs was markedly influenced, and EGF staining in altered granular convoluted tubule (GCT) cells showed highly positive as in the normal GCT cells. Testosterone treatment after duct ligation as well as hormone treatments before sacrifice were also done. Testosterone effects on duct-ligated SMGs were evident in degranulated GCT cells and duct-like structures and in enhanced secretory granules of degenerated ductal epithelia.These changed GCT cell's findings were observed in EGF reaction, and lectin bindings for PNA and SBA. Keratins (KLIM) in ductligated SMGs appeared in duct-like structures, whereas they decreased in proportion to the number of secretory granules after hormone treatment. Testosterone effects on GCT cells and degranulated tubules appeared till the 7th day after injection, and were not evident at the 2nd and 3rd weeks, irrespective of different treatment methods : with pre-ligated testosterone and post-ligated groups and with castration.It is well known that histologic changes following duct ligation of salivary glands show acinar atrophy and degranulation of granular convoluted tubules (GCTs) in the early stage and duct-like structures or cystic lesions with fibrous proliferation in the later stage (3,21,22,(24)(25)(26). It has recently been pointed out that immunohistochemically detectable epidermal growth factor (EGF) and nerve growth factor (NGF) in the GCT cells in this alterative progress of ligated SMGs were markedly reduced when followed by ligation (24), whereas keratin (KLIM) gradually developed in degranulated GCT cells, and lectin binding affinities in acinar and GCT cells were changed depending on histologic figures (26,27). GCT cells in mice submandibular glands (SMGs) are unique structures containing a lot of growth factors (EGF and NGF etc.) (1,8,15,17) and they are strongly influenced by male hormone administration (2,5,7,12,18), and are dramatically reduced by 481

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Submaxillary Gland Epidermal Growth Factor: A Sensitive Index of Biologic Androgen Activity

Cited by 87 publications

References 0 publications

Prostatic acid phosphatase is the main acid phosphatase with 5′-ectonucleotidase activity in the male mouse saliva and regulates salivation

Prostatic acid phosphatase is the main acid phosphatase with 5′-ectonucleotidase activity in the male mouse saliva and regulates salivation

Biologically Active Polypeptides in Mouse Submandibular Gland

Immunohistochemical observations of epidermal growth factor, keratin proteins and lectin binding on effects of testosterone administration in duct-ligated submandibular glands of mice.

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