Appearance of specific proteins in rat epididymis during postnatal development

In the immature 30-day-old caput and cauda epididymides of the rat, only a single prealbumin protein was visible. Additional epididymis-specific proteins appeared in the caput on day 45, coinciding with the entry of testicular fluid containing first wave of spermatozoa. In the cauda epididymides, additional proteins appeared only on day 50. These results indicate that the functional differentiation of caput precedes that of the cauda epididymidis.     

Postnatal development and regulation of beta-hexosaminidase in epithelial cells of the rat epididymis

beta-Hexosaminidase (Hex) catalyzes the hydrolysis of terminal sugar residues from a number of substrates such as GM2 gangliosides, glycoproteins, glycolipids, and glycosaminoglycans. As an enzyme present in lysosomes of epithelial cells of the adult rat epididymis, it serves to degrade substances endocytosed from the epididymal lumen. In this way, it modifies and creates a luminal environment where sperm can undergo their maturational modifications. In this study, the postnatal developmental pattern of expression of Hex was examined in animals from days 7-56. In addition, the role of testicular factors on Hex expression in the different cell types and regions of the epididymis of adult rats was examined in orchidectomized and efferent duct-ligated rats. Both parameters were examined on Bouin-fixed epididymides in conjunction with light microscope immunocytochemistry. At postnatal day 7, the epithelium of the entire epididymis was unreactive for anti-Hex antibody. By day 21, narrow and clear cells of their respective regions became reactive, whereas basal cells became reactive only by day 29. Principal cells displayed only an occasional reactive lysosome at day 21, several by day 29, and numerous reactive lysosomes by day 39, comparable to the region-specific distribution noted for 90-day-old animals, and at an age when high androgen levels are attained. Thus, postnatal onset of Hex expression varies according to the different cell types of the epididymis, suggesting different regulatory factors. This finding was confirmed from studies employing adult orchidectomized and efferent duct-ligated adult rats. Indeed, in all experimental animals, Hex immunostaining in narrow, clear, and basal cells was intense and comparable to control animals. In contrast, there was a notable absence of lysosomal staining in principal cells at all time points after orchidectomy, which was restored, however, following testosterone replacement. No effect on Hex expression was observed in efferent duct-ligated animals. Taken together, the data suggest that Hex expression in lysosomes of principal cells is regulated by testosterone or one of its metabolites. However, the expression of Hex being independent of testicular factors in narrow, clear, and basal cells of adult animals, but occurring at different time points during postnatal development, suggests that different regulatory factors are responsible for onset of Hex expression in these cell types during development.     

Spatiotemporal expression patterns of natriuretic peptides in rat testis and epididymis during postnatal development

Natriuretic peptide (NP) family is composed of atrial, brain and C‐type NP (NPPA, NPPB and NPPC). Here, we aimed to investigate NP expression in testis and epididymis during postnatal development. NPPA expression was observed in gonocytes at prepubertal period but in only spermatocytes in pachytene and leptotene/zygotene stage at pubertal period. In prepubertal and pubertal periods, we detected NPPB expression in only Leydig cells. However, NPPC expression was detected in all of the gonocytes and Sertoli cells, spermatocytes and some interstitial cells in prepubertal and pubertal periods. In postpubertal and mature periods, NPPA and NPPB staining were detected in Leydig cells, elongated and round spermatids but not in spermatogonia and spermatocytes. However, we observed NPPC expression in all cells of the seminiferous tubules and Leydig cells in the postpubertal and mature periods. Epididymal epithelium showed intense NPPC expression during postnatal period but weak NPPA and NPPB expression in prepubertal and pubertal periods. The expression of three NPs in the testis significantly increased after puberty. In conclusion, puberty had a significant effect on NP expression in testis. Unlike NPPA and NPPB, expression of NPPC in all cells of the seminiferous tubule suggests that NPPC is effective in each step of spermatogenesis.     

Structural features of cultured epithelial cells from the adult rat epididymis

Epithelial cells isolated from the caput epididymidis of adult rats were placed in primary culture and examined daily for ten days for changes in external anatomy, reorganization of cytoskeletal components, maintenance of characteristic cytoplasmic features, and response to media formulated to minimize nonepithelial cell proliferation. Significant cell attachment to the substrate began after the first 24 hours of culture. After attachment, the cells underwent a progressive flattening and became closely applied to the substrate. This was accompanied by a redistribution of microvilli on the cell surface and a reorganization of cytoskeletal elements within the cell. After flattening, the cultured cells displayed an extensive array of 10-nm filaments which were associated with the desmosomes attaching adjacent cells. Immunofluorescence studies demonstrated that these were keratin-containing intermediate filaments and 2-D gel electrophoresis of intact cells and cell cytoskeletons revealed that a family of "keratin-like" polypeptides were major components of the cells. Epithelial cell attachment, morphology, and maintenance in the primary culture were unaffected by D-valine, cytosine arabinoside, or both; however, these agents, either individually or in combination, reduced significantly the number of cells incorporating 3H-thymidine. These data show that isolated epithelial cells retain some differentiated structural features that characterize the intact cell and that enriched cultures of epithelial cells can be maintained under conditions where fibroblast proliferation is inhibited.     

Effect of testosterone on epithelial cell proliferation in the regressed rat epididymis

It is well established that testosterone plays a crucial role in maintaining the integrity of epididymal structure and function. However, the role of testosterone in restoring the cellular architecture of the regressed epididymis is not well known. The present study was undertaken to test the hypothesis that testosterone triggers the regressed epididymis by re-expanding existing cells and inducing cell proliferation. Testosterone-dependent epididymal morphology was evaluated in orchidectomized, regressed rats after initiation of treatment with testosterone. Besides that, the proliferative activity of epithelial cells in all regions of the epididymis of the orchidectomized, regressed rats was assessed at 1, 3, 7, and 28 days after testosterone replacement. Epithelial cell proliferation decreased after testosterone withdrawal and increased following testosterone administration. We found that bromodeoxyuridine incorporation and proliferating nuclear antigen expression increased significantly 3 days after testosterone replacement in all regions of the regressed epididymis except in the initial segment. The highest mitotic activity was seen in the corpus epididymidis at 3 days postimplantation. Using specific markers for each cell type, we found no significant changes in the proportion of each cell type compared with the control. We observed labeled nuclei in all epithelial cell types in the control; however, principal cells were the major cell types that responded to testosterone after regression. These observations demonstrate that the mammalian epididymis is not a static tissue without any significant cell renewal, either under control conditions or when androgen exposure is altered, thus providing new insight in the role of androgen in restoration and maintenance of the architecture of the epididymis.     

Gamma-glutamyl transpeptidase activity in the epididymis during fetal and postnatal development in rats.

The histochemical and biochemical distributions of gamma-glutamyl transpeptidase (gamma-GT) were investigated in the epididymis of rats during fetal and postnatal development. In the epididymal homogenates, gamma-GT activity was detected on the fifth day after birth. A sharp increase was observed after 30 days of life in the caput homogenates. Moderate levels of the enzyme were found in the cauda epididymis. Gamma-GT is histochemically detected from the 15th day of gestation in Wolffian ducts and in 17- to 18-day-old fetuses in newly differentiated epididymal tubules. Enzyme activity, was associated with the plasma membranes (apical, lateral, and basal), was preponderant on the apical part of the epithelial cells. During the first 15 days of the postnatal life, the histochemical reaction intensities were identical from the caput to the cauda epididymidis. From the 18th day onwards, enzyme activity decreased in the corpus and in the cauda, while gamma-GT increased in the caput epididymidis, and a strong activity was found on the apical surface of epithelial cells. Weak or moderate gamma-GT activity of spermatozoa in the caput tubules, increasing steadily from caput to cauda epididymidis, suggests that gamma-GT may be related to the functional maturation of spermatozoa.     

Expression profile of Toll-like receptor 4 in rat testis and epididymis throughout postnatal development

Toll-like receptors (TLRs) belonging to pattern recognition receptors are involved in maintaining testicular and epididymal immune homeostasis. The purpose of the current study was to investigate TLR4 expression in rat testis and epididymis throughout postnatal development. Weak staining was detected in peritubular myoid cells and immature Sertoli cells while no staining was observed in gonocytes during prepubertal period. However, TLR4 expression began to appear in spermatocytes in pubertal period and gradually increased in spermatids. An intense staining was observed in steps 5–19 spermatids in post pubertal and mature periods. Similarly, TLR4 expression in the testes steadily increased from pubertal period to mature period. Puberty also caused a significant increase in TLR4 expression in epididymis. TLR4 expression in cauda epididymis was lower as compared to those of other epididymal segments. The majority of epididymal epithelial cells exhibited apical TLR4 expression, whereas basal cells showed intense intracytoplasmic immunoreaction. We detected an intense staining in epididymal smooth muscle cells. The expression levels of TLR4 showed dynamic changes in both spermatogenic cells, and entire testicular and epididymal tissues during postnatal development. These results suggest that TLR4 expression contributes not only to inflammation but also to the development of spermatogenic cells.     

Presence of neuroendocrine cells during postnatal development in rat prostate: Immunohistochemical,molecular, and quantitative study

BACKGROUND: This work was undertaken to study the prostate neuroendocrine cells (PNEC) during the post-natal development of rats. METHODS: Forty male Wistar rats (pre-pubertals, pubertals, young, and aged adults) were used for immunohistochemistry of chromogranin A (cgA), serotonin (SER), and protein gene product 9.5 (PGP9.5). They were also evaluated for numerical cell density (NV SER) and PNEC number per prostate (N SER). Five additional young adult rats were used for a RT-PCR study (mRNA cgA detection). RESULTS: Weak immunoreactivity to cgA was observed in pubertal rats. No PNEC immunostained to PGP 9.5 was observed. Cells expressing SER were detected in all the groups exclusively located in periurethral ducts. The NV SER increased significantly in pubertal animals. In aged animals, it decreased to levels observed in pre-pubertal rats. The N SER increased significantly from pre-pubertal to young adults, decreasing in aged adults. There was weak production of cgA mRNA, with more expression in the dorsal prostate. CONCLUSIONS: PNEC differ in rats when compared to humans: they are weakly immunopositive to cgA, do not express PGP 9.5, only show immunoreactivity to SER, and do not appear in acini. The changes in the amount of rat PNEC during the post-natal development suggest an androgenic influx. PNEC might regulate the contractility of periurethral ducts.     

Acquisition of androgen-mediated expression of mouse vas deferens protein (MVDP) gene in cultured epithelial cells and in vas deferens during postnatal development

We used cultured vas deferens epithelial cells (VDECs) as a model system to determine the conditions that allow mouse vas deferens protein (MVDP) gene expression and acquisition of androgen responsiveness. On the basis of Northern blot analysis, the mvdp gene is constitutively expressed at very low levels in prepubertal VDECs grown on collagen-coated plastic or on microporous membrane inserts. In the presence of dihydrotestosterone (DHT), mvdp messenger RNA levels dramatically increased in cells cultured on microporous membrane inserts and stayed unchanged in cells grown on matrix-coated plastic. Epithelial cells derived from fetal vas deferens were able to synthesize MVDP in response to DHT, and the presence of fetal mesenchymal cells did not influence MVDP production. Providing the cells with a culture procedure that permits access to the basolateral membranes and caters to the polarity requirements of the cell is a prerequisite for androgen induction of MVDP gene expression. The results also point to a role for epidermal growth factor, insulin, and tyrosine kinase activity in mediating the action of androgen on mvdp gene expression. In vivo studies show that the first expression of the mvdp gene between 5 and 7 days postpartum is not associated with major structural changes in the epithelium. The acquisition of a mature phenotype by epithelial and peritubular contractile cells, between 10 and 20 days, correlates with androgen dependency of the mvdp gene. We propose that cell differentiation and polarization on a matrix-coated microporous membrane reproduces some of the events that are necessary for acquisition of androgenic responsiveness of the mvdp gene during postnatal development.     

Expression and localization of Smadl, Smad2 and Smad4 proteins in rat testis during postnatal development

Aim: To study the expression and regulation of Smadl, Smad2 and Smad4 proteins (intracellular signaling molecules of transforming growth factor-β family) in rat testis during postnatal development. Methods: The whole testes were collected from SD rats aged 3, 7, 14, 28 and 90 (adult) days. The cellular localization and developmental changes were examined by immunohistochemistry ABC method with the glucose oxidase-DAB-nickel enhancement technique. Quantitative analysis of the immunostaining was made by the image analysis system. The Smads proteins coexistence in the adult rat testis was tested by the double immune staining for CD14-Smad4 and Smad2-Smad4. The protein expression of Smad during rat testicular development was examined by means of Western blots. Results: Smadl, Smad2 and Smad4 were present throughout testicular development. The immunostaining of Smadl and Smad2 were present in spermatogenic cells. A positive immunoreactivity was located at the cytoplasm, but the nucleus was negative. Smadl wa     

Immunolocalization of CA II and H+ V-ATPase in epithelial cells of the mouse and rat epididymis

Acidification of the epididymal lumen has been suggested to play an important role in sperm functions; however, the cell types, pumps, and mechanisms involved have not been fully addressed. In this study, carbonic anhydrase II (CA II) and a 67-kd subunit of Neurospora crassa vacuolar proton adenosinetriphosphatase (H+ V-ATPase) pump were immunolocalized using light microscopy and electron microscopy (EM) in the epididymis of rats and mice. In both animals, narrow cells, identified in the initial segment and intermediate zone of the epididymis, contained numerous small vesicles in their apical region, often cup-shaped in appearance. In the mouse but not rat, these cells also possessed numerous cisternae of smooth endoplasmic reticulum, suggesting steroid synthesis; and cytoplasmic blebs of their apical cell surface, which appeared to detach, suggesting apocrine secretion. Anti-CA II antibody was immunocytochemically localized in the light microscope within narrow cells but not over any other cell types of the entire epididymis. Anti-H+ V-ATPase antibody was also localized in narrow cells of the initial segment and intermediate zone; as well as clear cells of the caput, corpus, and cauda regions. Using EM, gold particles for anti-CA II and H+ V-ATPase antibodies were noted in the apical region of narrow cells in relation to the numerous, small, cup-shaped vesicles. Although CA II was mainly located in the cytosol near these vesicles, H+ V-ATPase appeared on their delimiting membrane and on the apical plasma membrane of these cells. A similar distribution was noted for H+ V-ATPase in clear cells. The nature of the small vesicles of the apical region of narrow cells was examined with electron-dense fluid phase tracers that were introduced into the epididymal lumen. The tracers appeared within these vesicles and a few endosomes 1 hour after injection, suggesting that they contact the apical plasma membrane. Since these vesicles are also related to CA II and H+ V-ATPase, the data suggests that, as the site of proton production, the vesicles recycle to and from the apical cell surface, and in this way, deliver protons to the epididymal lumen for acidification. Clear cells and their expression of H+ V-ATPase may also serve in this function. In summary, both narrow and clear cells appear to be involved in luminal acidification, an activity that may be essential for sperm as they traverse and are stored in the epididymis.     

Expression and localization of Smad1, Smad2 and Smad4 proteins in rat testis during postnatal development

Aim：To study the expression and regulation of Smad1,Smad2 and Smad4 proteins(intracellular signaling molecules of transforming growth factor-β family)in rat testis during postnatal development.Methods:The whole testes were collected from SD rats aged 3,7,14,28 and 90(adults)days.The cellular localization and developmental changes were examined by immunohistochemistry ABC method with the glucose oxidase-DAB-nickel enhancement technique.Quantitative analysis of the immunostaining was made by the image analysis system.The Smads proteins coexistence in the adult rat testis was tested by the double immune staining for CD14-Smad4 and Smad2-Smad4.The protein expression of Smad during rat testicular development was examined by means of Western blots.Results: Smadl,Smad2 and Smad4 were present throughout testicular development.The immunostaining of Smad1 and Smad2 were present in spermatogenic cells.A positive immunoreactivity was located at the cytoplasm,but the nucleus was negative,Smadl was immunolocalized at the d14,d28 and adult testes,while Smad2,at the d7,d14,d28 and adult testis.There was positive immunoreaction in the Sertoli cells and Leydig cells as well.The immunolocalization of Smad4 was exclusively at the cytoplasm of Leydig cells and the nuclei were negative throughout the testicular development.No expression was detected in the germ cells.The results of image and statistical analysis showed that generally the expression of Smad1,Smad2 and Smad4 in the testis tended to increase gradually with the growth of the rat.Conclusion;The present data provide direct evidences for the molecular mechanism of TGF-β action in rat testes during postnatal development and spermatogenesis.     

Immunohistochemical localization of metallothionein in the rat prostate gland during postnatal development

Immunocytochemical and electrophoretic techniques were used to investigate the presence of metallothionein, a metal-binding protein, in the dorsolateral and ventral lobes of the developing rat prostate. Male rats aged 7 and 14 days were injected subcutaneously with 6 and 20 mg/kg body weight of cadmium and zinc, respectively, or with saline for controls, 24 h prior to tissue sampling. Immunohistochemical localization of metallothionein was observed in the epithelial tissues of the dorsolateral prostate from 7 and 14 day-old animals and in 1 day-old untreated rats. This staining pattern did not appear to be significantly affected by cadmium or zinc treatment. In contrast, metallothionein localization in the ventral prostate decreased with age but demonstrated a slight response to metal-ion treatment in the 7 day-old animals. Electrophoretic and immunoblot analysis confirmed the presence of metallothionein in the control and metal-induced prostate samples from neonatal rats. Lobe-specific differences in localization suggest a functional significance for metallothionein, independent of inducible protein.     

Expression of the p63 and Notch signaling systems in rat testes during postnatal development: comparison with their expression levels in the epididymis and vas deferens

The role of tubular structures that contribute to the passage of spermatozoa is not solely passive; these structures actively contribute to their own functions, although these tubules and ducts are contiguous and collaborate in the development of the male gamete along their lengths. The testis has the specific function to generate spermatozoa and spermatozoa undergo numerous changes as they pass through the epididymis. A member of the p53 family of genes, p63, is highly expressed in the basal layers of epithelial tissues and plays a key role in maintaining their cell populations, whereas Notch 1 and its ligand Jagged 2 have an important role in the differentiation of germ cells and Jagged 2 is up-regulated by TAp63, one of the p63 isoforms, which transactivates p53 target genes and induces apoptosis. Although the presence of p63 in most epithelia is established, the role of p63 and its possible relationship with the Notch system in the seminiferous epithelium have not been examined. Therefore, we investigated the expression of p63, Jagged 2, and Notch 1 in the testis during postnatal development in comparison with their expression levels in the vaso-epididymal epithelium. In the testis, the expression of TAp63 mRNA increased at day 14 after birth and the expressions of Jagged 2 and Notch 1 mRNA increased at day 16 after birth, suggesting that TAp63-mediated Jagged 2 induction activates the Notch signaling system. On the other hand, the strong signal of DeltaNp63 mRNA was already recognized in the vas deferens at day 0 after birth and advanced chronologically along the duct to the caput epididymis and p63 protein was expressed in basal cells in their epithelium, whereas the mRNAs of Jagged 2 and Notch 1 were maintained at a low level. Consequently, examination of our data raises the probability that TAp63 has an important role for maintenance of germ cell numbers, triggering or balancing the development, differentiation, and apoptosis of germ cells in the testis, which is completely different from the role of DeltaNp63 in other epithelial tissues.     

Expression and regulation of aquaporins 1, 8, and 9 in the testis,efferent ducts,and epididymis of adult rats and during postnatal development

Aquaporins (AQPs) are membrane protein channels that allow the rapid passage of water through an epithelium containing tight junctions. In the present study, light microscope immunocytochemistry was utilized to localize several members of the AQP family in the testis, efferent ducts, and epididymis of normal adult animals during postnatal development and after various experimental procedures on adult animals. In the testis of normal adult animals, AQP-8 was expressed exclusively in Sertoli cells, while AQP-9 outlined Leydig cells. In the efferent ducts, AQP-1 was expressed on the microvilli, basolateral plasma membranes, and apical endosomes of the nonciliated cells and cilia of ciliated cells, while AQP-9 was present only on the microvilli of nonciliated cells. In the epididymis, AQP-9 was localized to the microvilli of the principal cells of all regions, with the most intense reaction being noted in the initial segment and cauda regions. The clear cells of the cauda region expressed only AQP-9. AQP-1 was not expressed in the testis or the epididymal epithelium, but it was expressed over the endothelial cells of the vascular channels of the efferent ducts and epididymis. After efferent duct ligation or orchidectomy, there was no change in the expression of AQP-1 or -9 over the microvilli or cilia of epithelial cells in the case of the efferent ducts, suggesting that testicular factors do not regulate their expression in this region. In contrast, AQP-9 expression in the principal cells of the initial segment, but not of other regions, and also in the clear cells of the cauda region was dramatically reduced after both treatments. As the expression was not restored to control levels by testosterone replacement, the data suggest that a luminal factor(s) derived from the testis regulates AQP-9 expression in the principal cells of the initial segment and in the clear cells of the cauda region. Postnatal studies revealed that the expression of AQP-1 and -9 in the different cell types of the efferent ducts and epididymis occurred between days 7 and 29, eliminating sperm and high androgen levels as possible regulating factors. Taken together, these data suggest cell specificity with respect to the expression of AQP-8 and -9 in the testis. In the efferent ducts and epididymis, specificity exists in cell, region, and tissue distribution with respect to the expression of AQP-1 and -9, and their expression does not appear to be regulated by androgens.     

Are eosinophil leucocytes involved in the oestrogenic response of the postnatal rat epididymis?

The effects of oestrogens and androgens, alone or in combination, on several epididymal parameters have been studied in 15-day-old rats after neonatal treatment. Oestrogens induced several responses, such as increased growth of the fibromuscular stroma and eosinophil leucocyte accumulation, whereas the proliferative activity of the epithelium was decreased significantly. Otherwise, the density of intra-epithelial leucocytes was not modified. Different oestrogen-induced responses, such as the increase in volume of the fibromuscular stroma and eosinophil leucocyte accumulation were inhibited by treatment with testosterone, whereas dihydrotestosterone had no appreciable effect. This study raises the possibility that eosinophils are mediators of some of the oestrogenic responses in the early postnatal rat epididymis.     

Differential expression of c-erb B2/neu, epidermal growth factor receptor, cytokeratin 8, and the prostatic steroid-binding protein gene in rat ventral prostate during postnatal development

BACKGROUND: The development and progression of prostate neoplasia may recapitulate the early developmental pattern of expression of genes in the prostate. The study of prostate development may, therefore, provide insights into the molecular mechanisms important in prostate neoplasia and reveal new markers. METHODS: We compared postnatal expression of four genes: neu and epidermal growth factor receptor genes (EGFR), androgen-upregulated in the ventral prostate of adult rats (C-3), and androgen-repressed (CK8) in Sprague-Dawley rats. In situ hybridization was performed on prostate frozen sections collected on postnatal days 1, 5, 10, 15, 20, 30, and 60 from five rats per day. Staining intensities for antisense probes specific for each gene were determined relative to day 1 intensity. RESULTS: Growth factor receptors including neu and EGFR may be coordinately regulated in the basal-cell population during prostate development. CK8 and C-3 show evidence of similar androgen regulation during development. CONCLUSIONS: CK8 and C-3 have distinct patterns of expression in the postnatal period of development and these genes may be good markers of differentiation. Both neu and EGFR may be involved in androgen-independent growth of basal cell population in prostate. Prostate 47:164-171, 2001.     

反义寡核苷酸抑制结肠癌细胞bcl-2基因的表达并增强凋亡的研究

目的　观察反义寡核苷酸抑制结肠癌细胞bcl 2基因的表达并诱导凋亡和增强化疗的敏感性。方法　应用反义硫代寡核苷酸 (bcl 2SON)和顺铂共同处理结肠癌细胞系SW62 0 ,通过流式细胞仪观察其bcl 2蛋白表达的变化 ,并通过原位末端标记法 (TUNEL)染色和流式细胞仪检测细胞凋亡指数。结果　用bcl 2SON处理过的SW62 0细胞其bcl 2蛋白平均荧光强度 (MFI)为(40 .3± 8.7) %与空白对照及随机链对照组相比 ,差异有非常显著性 (P <0 .0 1 ) ,表明导入反义bcl 2后可明显抑制结肠癌细胞的bcl 2蛋白的表达。经bcl 2SON和 1 0mg/L顺铂共同处理的SW62 0细胞凋亡指数为 (64 .7± 8.4) % ,显著高于单纯顺铂处理组的 (2 3 .6± 6 .3) % (n =5 ,P <0 .0 1 )以及单纯bcl 2SON处理组的 (2 7.5± 5 .1 ) % (n =5 ,P <0 .0 1 )。而未经处理的对照组SW62 0细胞凋亡指数则为 (8.5± 1 .2 ) % ,显著低于后两组 (n =5 ,P <0 .0 5)。结论　bcl 2SON可通过抑制结肠癌细胞 (SW 62 0 )bcl 2蛋白的表达 ,诱导其凋亡 ,增强对化疗药物的敏感性     

Glucocorticoid receptor distribution in rat testis during postnatal development and effects of dexamethasone on immature peritubular cells in vitro

In this study, the occurrence of the glucocorticoid receptor in the rat testis during early stages of postnatal development and its potential functional significance were investigated. Quantitative analyses of immunohistochemically labelled paraffin sections revealed that the receptor was present during all stages of postnatal development in the nuclei of interstitial cells such as Leydig cells, macrophages and fibroblasts, and endothelial cells of blood vessels. The labelling index increased initially, with maximum levels reached within the second week of postnatal development, and decreased thereafter. Within the seminiferous tubules, the glucocorticoid receptor could be detected in the nuclei of germ cells as well as Sertoli cells, reaching the highest levels in 3-week-old rats, mainly due to immature germ cell staining. In contrast, approximately 50% of the peritubular cell nuclei were stained throughout postnatal development. In vitro experiments on immature and immortalized peritubular cells demonstrated a dose-dependent and significant decrease in proliferation and fibronectin secretion after administration of dexamethasone. The data of this study suggest that glucocorticoids have a consistently repressive effect on peritubular cells throughout postnatal development. In summary, labelling of germ cells, especially in immature rats, might indicate an inhibition of spermatogenesis by corticosteroids.