Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that disruption or damage to the seminiferous tubules by radiation, antiandrogen, vitamin A deficiency or experimental cryptorchidism causes Leydig cell hypertrophy and hyperplasia, suggesting that Sertoli cells secrete a mitogenic factor(s) that stimulates Leydig cell proliferation. To study the possible paracrine regulation of Leydig cell proliferation by Sertoli cells, highly purified Leydig cells and Sertoli cells were co-cultured in a two-chambered co-culture system. Our results revealed that co-culture of immature rat Sertoli cells with Leydig cells stimulated Leydig cell DNA synthesis by 19-fold, increased cell number by about 3.9-fold and increased the labeling index from 0.5% to 15.8%. In addition to these changes, co-culture reduced Leydig cell testosterone formation and luteinizing hormone (LH) receptor levels, and dramatically altered the morphology of Leydig cells. The addition of concentrates from Sertoli cell conditioned medium (SCCM) mimicked these biological effects. The Leydig cell mitogenic activity in SCCM was trypsin sensitive and inactivated by boiling for 2 h, suggesting that it is a protein. However, it was resistant to acid and dithiothreitol. The molecular weight of this putative factor(s) is above 10 kDa. The responsiveness of Leydig cells to this mitogenic protein(s) decreased with age, whereas the secretion of this protein(s) by Sertoli cells in culture did not change with age. The addition of 10 ng/ml of follicle stimulating hormone (FSH) dramatically decreased the mitogenic activity in SCCM, indicating that the secretion of this mitogenic factor(s) is inhibited by FSH. This paracrine factor(s) may be as yet an unidentified testicular growth factor(s) because it differs in molecular weight, stability and other characteristics from all previously reported Sertoli cell-produced or expressed growth factors.
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PMID:A Sertoli cell-secreted paracrine factor(s) stimulates proliferation and inhibits steroidogenesis of rat Leydig cells. 789 20

We have cloned a type of cDNA for a functional glandular kallikrein, designated as mouse Klk21 (mKlk21), from the adult mouse testis cDNA library. mKlk21 was expressed in the kidney, submaxillary glands, and testis of the mouse. In the testis, mKlk21 mRNA was detectable at 4 wk of postnatal development and became more prominent thereafter. The mKlk21 gene was expressed exclusively in the Leydig cells of adult mice. When Leydig cells isolated from 2-wk-old mouse testis were cultured in the presence of T, mKlk21 expression was induced significantly. Active recombinant mKlk21 showed trypsin-like specificity, favorably cleaving Arg-X bonds of synthetic peptide substrates. The enzyme activity was strongly inhibited with typical serine protease inhibitors. mKlk21 hydrolyzed casein, gelatin, fibronectin, and IGF-binding protein-3 (IGFBP-3). As in mKlk21, IGF-I and IGFBP-3 were expressed in the Leydig cells of the adult mouse testis, although the transcript of IGFBP-3 was not detected in all of the observed cells. The culture medium of Leydig cells isolated from adult mouse testes contained an mKlk21-like enzyme activity capable of degrading IGFBP-3. These results suggest that mKlk21 plays a role in Leydig cell function in the adult mouse testis.
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PMID:Mouse testicular Leydig cells express Klk21, a tissue kallikrein that cleaves fibronectin and IGF-binding protein-3. 1160 60

The objective of this study was to investigate mast cells and iNOS expression in testis tissue, and to correlate these results with spermatogenic disorders. A total of 136 testicular biopsies were obtained from the testes of 80 patients with infertility. Their age ranged from 21 to 45 years. The biopsy specimens were immunohistochemically stained with antihuman tryptase for mast cells. In each section, all interstitial fields were evaluated for the total number of mast cells as well as the total number of Leydig cells. The number of mast cells per Leydig cell was calculated and recorded as mast cell index. Immunohistochemical iNOS staining was evaluated semiquantitatively according to intensity and the proportion of the stained cells. There was a significant increase of the mast cell index in all groups with testicular disorder compared with normal spermatogenesis group (p < 0.05). Increase of the index was in the order of hypospermatogenesis, maturation arrest and SCO, and index of SCO group was especially higher, i.e, more than twice than other groups. iNOS score was significantly higher in the SCO group than in the men with normal spermatogenesis, hypospermatogenesis, and maturation arrest (p < 0.05). Finally, a significantly statistical correlation was found between the iNOS score and mast cells index (r = 0.758, p = 0.001). Increase of mast cell index was observed in the groups of infertile testis, and high expression of iNOS in Leydig cells was associated with the highest mast cell index in SCO, the lesion with the most severe damage of the germ cell.
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PMID:Relationship between mast cell and iNOS expression in testicular tissue associated with infertility. 1580 70

The occurrence of various serine proteinases and serine proteinases inhibitors (SERPINs) was investigated by RT-PCR in whole testes of 1-, 3-, and 8-wk-old mice in crude and enriched germ cell fractions, mouse Leydig tumor cells (mLTC-1), and primary cultures of 3- and 8-wk-old enriched fractions of Leydig cells and 3-wk-old Sertoli cells. New members were identified in the testis protease repertoire. Within the Leydig repertoire, a PCR product was found for plasminogen activators urokinase plasminogen activator (uPA) and tissue plasminogen activator (8-wk-old cells), matriptase-2 (mLTC-1), kallikrein-21, SERPINA5, SERPINB2 (primary cultures), and serine peptidase inhibitor Kunitz type 2 (SPINT2). The gonadotropin regulation was explored by semiquantitative RT-PCR, using steroidogenic acute regulatory protein (StAR) as a positive control. Matriptase-2, kallikrein-21, SPINT2, and SERPINA5 were down-regulated, whereas uPA and its receptor were up-regulated by human chorionic gonadotropin (hCG) via cAMP in the mLTC-1 cells. Positive effects were observed transiently after 1-8 h of hCG exposure, and negative effects, first evidenced after 6 h, lasted 48 h. The hCG-induced effects were confirmed in primary cultures. In addition, SERPINB2 was augmented by hCG in primary cultures. Addition of either trypsin or protease inhibitors did not alter the hCG-induced surge of StAR. Because hCG regulated proteases and SERPINs (whereas testosterone did not), it could alter the proteolytic balance of Leydig cells and consequently the metabolism of extracellular matrix components. Therefore, even though a direct interplay between the early hCG-induced surge of uPA and StAR is unlikely, our data together with the literature suggest that extracellular matrix proteins alter Leydig cell steroidogenesis.
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PMID:The mouse testis is the source of various serine proteases and serine proteinase inhibitors (SERPINs): Serine proteases and SERPINs identified in Leydig cells are under gonadotropin regulation. 1674 Sep 73


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