Growth, morphogenesis, and differentiation during mouse prostate development in situ, in renal grafts, and in vitro

BACKGROUND: In vitro organ culture and renal grafting of the urogenital sinus (UGS) have both been used as models of prostate development. However, neither has been rigorously examined for its fidelity to replicate the canonical process of prostate differentiation in situ. METHODS: We assessed size, morphology, histology, and the mRNA expression of differentiation marker genes of the E14 male mouse UGS grown for 0-28 days as sub-renal capsule allografts in nude mice or in culture containing androgen and compared these to UGS development in situ. RESULTS: Development of grafted tissues was morphologically and histologically similar to development in situ but differentiation occurred more rapidly. UGS growth in organ culture resulted in bud formation, but did not trigger cellular differentiation. However, the potential for differentiation was maintained and could be rescued by grafting tissues into nude mice. CONCLUSIONS: In vitro organ culture and renal grafting of UGS tissues may be appropriate models for studying prostatic bud formation, but only grafting is an appropriate model for prostatic differentiation.     

Prostate gland growth during development is stimulated in both male and female rat fetuses by intrauterine proximity to female fetuses

In rodents, steroid hormones are transported between adjacent fetuses, and male or female fetuses that develop in utero between female fetuses (2F males or 2F females) have higher serum levels of estradiol and lower serum levels of testosterone relative to siblings of the same sex that develop between two male fetuses (2M males or 2M females). The present study was prompted by the prior unexpected finding that as adults, 2F male mice have an enlarged prostate, and increased numbers of prostatic androgen receptors relative to 2M males. We examined prostate development in both male and female rat fetuses from different intrauterine positions using computer-assisted, 3-dimensional reconstruction of the urogenital complex. In males, this included the prostate, seminal vesicles and utricle (a remnant of the Müllerian ducts), while in females it included development of prostatic glandular buds. The mean cross-sectional area of developing prostatic epithelial buds, utricle and seminal vesicles was significantly increased in 2F male relative to 2M male fetuses. In female fetuses, prostatic bud development was significantly more likely to occur in 2F (67%) than in 2M (29%) animals. These findings suggest that the transport of a small supplement of estrogen from adjacent female fetuses enhances androgen-dependent accessory organ development. We also found that mRNAs encoding receptors for both estrogen and androgen were located in the mesenchyme of the developing male prostate. The localization of estrogen and androgen receptor mRNA in this region further suggests that the mesenchymal induction of prostatic epithelial growth involves both hormones. The cranial dorsolateral prostatic buds exhibited the greatest enlargement in 2F males. This region of the developing prostate in rats is comparable (that is the embryonic homologue) to the region exhibiting benign prostatic hyperplasia (BPH) during aging in men. We propose that the potential for pathological regrowth of the prostate during aging is imprinted by estradiol during fetal development.     

Antagonistic effects of cyproterone acetate and oestradiol on the development of the fetal rat prostate gland induced by androgens in organ culture

The influence of cyproterone acetate and 17beta-estradiol on the induction of the rat prostate gland by androgens has been investigated in organ culture. The gland develops from its "anlage," the urogenital sinus, as epithelial buds projecting from the urogenital epithelium into the surrounding mesenchyme. In 16.5-day-old male sinuses explanted in organ culture, testosterone or dihydrotestosterone induced such buds de novo; cyproterone acetate or 17beta-estradiol combined with the androgens competitively inhibit the bud formation in most explants. In contrast, in 18.5-day male sinuses both anti-androgens are ineffective, and prostatic buds develop. The difference in response suggests that in the older tissue, exposure to endogenous testosterone before explantation has already set in motion events leading to the differentiation of the gland that are irreversible.     

Regional differences in the inductive activity of the mesenchyme of the embryonic mouse urogenital sinus

Embryonic urogenital sinuses (UGS) of 16-day-old mice were divided into two or three zones (cranial half and caudal half; or cranial third, intermediate, and caudal thirds). Following tryptic digestion, these zones were separated into their mesenchymal (UGM) and epithelial (UGE) components. The cranial and caudal zones of the UGM were recombined separately with the different zones of the UGE or with adult mouse urinary bladder epithelium (BLE). Following four weeks of growth in syngeneic male hosts, tissue recombinants of cranial UGM + caudal UGE contained numerous prostatic ducts and urethral glands. Conversely, recombinants composed of caudal UGM + cranial UGE developed into fibromuscular tissue covered with urethral epithelium and did not contain prostate, but occasionally contained urethral glands. Urethral glands were usually present in grafts of cranial UGM + cranial UGE or in grafts of the intact intermediate third of the UGS. In heterotypic recombinants of the UGM + adult BLE, prostatic glands were induced only when cranial UGM was utilized. Urethral glands were not observed in tissue recombinants prepared with adult BLE. These data suggest that regional differences in mesenchymal inductive ability and epithelial responsiveness play a role in the harmonious morphogenesis of the male lower genitourinary tract.     

Tissue interactions and prostatic growth: II. Morphological and biochemical characterization of adult mouse prostatic hyperplasia induced by fetal urogenital sinus implants

Current hypotheses regarding the causes of human benign prostatic hyperplasia have implicated both steroid hormone imbalance and tissue interactions. To examine the role of the latter we have further investigated the phenomenon of urogenital sinus-induced hyperplasia of the adult mouse ventral prostate. Urogenital sinuses (UGS) or purified urogenital mesenchyme (UGM) from C3H mice were implanted into the ventral prostates or coagulating glands of 50- to 90-day-old BALB/c-nu/nu hosts. The animals were sacrificed at 15, 30, and 180 days postimplantation to establish time dependence. Wet weight and DNA content were used as measures of net growth. Glucose phosphate isomerase (GPI) isozyme analysis was used to determine the relative contributions of C3H and BALB/c cells to the enlarged chimeric ventral prostates. It was determined that the induced growth is time-dependent and that the UGS induces 2- to 4-fold more growth than UGM. GPI analysis shows that UGM-induced growth was composed primarily of host-derived cells whereas the UGS is composed nearly equally of host- and implant-derived cells. Histologic analysis reveals that the UGS implants induce marked epithelial proliferation. The proliferating glands occur in clusters, and the epithelium within the glands appears cribriform. Foci of postobstructive cystic atrophy are also found. Remnants of the implanted UGS are still present even at 180 days postimplantation. UGM-induced growth is of a more subtle nature and appears morphologically similar to the sham-operated controls. In view of the morphologic similarity with human disease, as well as the time and hormonal dependence of UGS-induced ventral prostatic hyperplasia, this model represents the basis for a unified hypothesis regarding the roles of tissue interaction and hormonal milieu in human benign prostatic hyperplasia.     

NAD(P)H‐quinone oxidoreductase 1 silencing aggravates hormone‐induced prostatic hyperplasia in mice

NAD(P)H‐quinone oxidoreductase 1 (NQO1) is a highly inducible flavoprotein known to involve in various cellular defence mechanisms. In this study, we explored whether NQO1 deletion affects hormone‐induced prostatic hyperplasia. Testosterone propionate (3 mg/kg, IP) was injected into wild‐type (WT) and NOQ1 knockout C57BL/6 mice (NQO1^?/?) for 14 consecutive days, and the samples were collected for biological and histochemical studies. The testosterone‐treated NQO1^?/? showed about 140% higher prostate weight than the testosterone‐treated WT, with enhanced connective tissue and hyperplastic glands formations. However, increased dihydrotestosterone level after testosterone treatment was not significantly different between the WT and NQO1^?/?. In contrast, the enhanced nuclear expression of proliferating cell nuclear antigen in NQO1^?/? prostate confirmed aggravated prostatic hyperplasia in NQO1^?/?. Moreover, the expression of heat shock protein (HSP) 90‐α was markedly increased in the NQO1^?/?, and this was supported by increased testosterone‐induced nuclear androgen receptor expression in NQO1‐silenced LNCaP cells. Testosterone‐induced prostate‐specific antigen expression was not reversed in NOQ1‐silenced cells after finasteride treatment. Although the exact role of NQO1 in prostatic hyperplasia remains unclear, the hyperplasia exacerbation due to NQO1 deletion might be independent of type 2 5α‐reductase and might be related to enhanced androgen receptor affinity due to enhanced HSP90‐α expression.     

Semiquantitative morphology of human prostatic development and regional distribution of prostatic neuroendocrine cells

BACKGROUND: The neuroendocrine cells of the human prostate have been related to proliferative disorders such as prostatic cancer. Their origin, distribution, and development have therefore been studied and discussed in terms of current stem cell concepts in the prostate. METHODS: Prostatic tissue specimens (n = 20) from human fetuses (n = 8), prepubertal and pubertal children (n = 8) and mature men (n = 4) were studied immunohistochemically using antibodies directed against neuroendocrine, epithelial as well as secretory markers. Semiquantitative computer-assisted evaluation of different epithelial and stromal components based on stereological principles was performed on azan-stained sections representative of all developmental stages. RESULTS: By the end of gestational Week 9, neuroendocrine (NE) cells appear in the epithelium of the urogenital sinus and are subsequently closely associated with the formation of urethral prostatic buds. The fetal and postnatal distribution pattern of NE cells within the gland is characterized by a relatively constant number of cells per gland similar to prostatic smooth muscle cells. Likewise, a density gradient exists with the highest density in the large collicular ducts and almost no NE cells in subcapsular peripheral acini. In peripheral ducts, the distribution is random. Maturation of the NE cells precedes that of the secretory cells by about 10-16 years. CONCLUSIONS: A second prostatic stem cell lineage, different from the urogenital sinus (UGS)-lineage is hypothesized originating from immature neuroendocrine cells. Being morphologically indistinguishable from the UGS-derived prostatic secretory cell lineage, it gives rise to neuroendocrine cells. Their presence is apparently important for proliferation regulation of the UGS-derived lineage of the prostate.     

Beta7 integrins contribute to skin graft rejection

BACKGROUND: Because integrins alpha4beta7 and alphaEbeta7 contribute to epidermotropism of T-cells during skin inflammation, we sought to study their role in skin allograft rejection. METHODS: Wild-type (WT) (beta7+/+) and beta7 gene knockout (beta7-/-) C57BL/6 (H-2(b)) mice and SJL/J (H-2(s)) mice served as donors and recipients of allogeneic skin grafts. An anti-integrin beta7 subunit mAb (FIB504.64) was used to treat WT beta7+/+ C57BL/6 recipients of skin grafts from SJL/J mice. RESULTS: WT C57BL/6 recipients acutely rejected skin from SJL/J mice in 13 days. In contrast, the survival of SJL/J skin on either beta7-/- gene knockout or WT C57BL/6 recipients treated with anti-beta7 subunit mAb, was prolonged by 6 to 7 additional days (P<0.01). The survival of skin allografts from either beta7-/- or beta7+/+ C57BL/6 mice received by SJL/J recipients was not prolonged (P >0.05). CONCLUSIONS: Beta7 integrins contribute to skin graft rejection, in accord with their role in mediating the epidermotropism of T-cells during skin inflammation.     

Adonesine A1 receptor and megalin defect in diabetic mice with early kidney disease

Objective To observe the effect of adenosine A1 receptor (A1AR) on the megalin defect in type 1 diabetic mice with early kidney disease. Methods 7-8 week-old, baseline body weight and fasting blood glucose matched wild type (WT) C57BL/6J mice were selected, and randomly divided into two groups: control group (n=6) and WT DM group (n=6). In the same way, male A1AR knock-out C57BL/6J mice were selected as A1AR-/- DM group (n=6). DM model was established by intraperitoneal injection of streptozocin. The blood glucose (BG), body weight (BW), kidney weight (KW), 24 h proteinuria (24hUP) and albumin creatine ratio (ACR) were measured at 4 weeks. The renal pathological lesion was observed and the expression of megalin in proximal tubules was examined by immunohistochemistry. The expression of caspase-1, IL-18 and A1AR were detected by Western blotting. Results At 4th week, compared with WT control mice, the BG, BW, KW and 24hUP of WT DM mice were increased significantly (n=6, P＜0.01), with the pathological glomerular enlargement, mesangial cell proliferation, extracellular matrix accumulation and renal tubule hypertrophy being observed. Immunohistochemistry revealed decreased expression of megalin, an important multiligand protein receptor on the brush border of proximal tubular epithelial cells in WT DM mice, which was correlated with 24hUP (r=-0.645, P＜0.01). Compared with the control mice, the expressions of caspase-1, IL-18 and A1AR were significantly increased in WT DM mice (P＜0.05). For A1AR-/- DM mice, more serious pathological lesion and megalin defect, together with increasing of casapase-1 and heavier proteinuria were observed than those in WT DM mice. Conclusion A1AR may play a protective role in megalin expression of diabetic mice with early kidney disease, in which the mechanism may be associated with caspase-1 related pyroptosis pathway. The details need further exploration.     

Progressive prostate hyperplasia in adult prolactin transgenic mice is not dependent on elevated serum androgen levels

BACKGROUND: Transgenic mice overexpressing the rat prolactin (PRL) gene under control of the metallothionein-1 promoter (Mt-1) develop a dramatic prostatic enlargement. These animals also display significantly elevated testosterone serum levels. In this study, we aim to clarify the role of circulating androgen levels in the promotion of abnormal prostate growth in the adult PRL transgenic mouse prostate. METHODS: Prostate morphology and androgen-receptor distribution patterns were analyzed in castrated and testosterone substituted adult PRL transgenic and in wild-type males. RESULTS: Progressive prostatic hyperplasia in adult PRL transgenic males was not affected by substitution to serum testosterone levels corresponding to wild-type. Furthermore, prolonged testosterone treatment in adult wild-type males did not produce any significant changes in prostate growth or morphology compared with wild-type controls. Immunohistochemical studies revealed a significantly increased proportion of androgen receptor positive epithelial cells in all lobes of the PRL transgenic prostate versus wild-type. CONCLUSION: The present study demonstrates that progressive prostate hyperplasia in adult PRL transgenic mice is not dependent on elevated serum androgen levels. Furthermore, prolonged androgen treatment in adult wild-type male mice appears to have no significant effect on prostate growth. In addition, our results suggest that prolonged hyperprolactinemia results in changes in prostate epithelial and stromal cell androgen receptor distribution.     

P-selectin and leukocyte microparticles are associated with venous thrombogenesis

OBJECTIVES: P-selectin inhibition has been found to limit venous thrombosis. We hypothesize that elevated levels of P-selectin will amplify thrombosis, mediated by procoagulant microparticles (MPs). METHODS: Male mice (Mus musculus, n659), 20 to 25 grams, underwent IVC ligation to induce thrombosis. Groups consisted of wild type (WT) C57BL/6 controls, mice with high circulating levels of soluble P-selectin (CT), P-selectin gene-interrupted knockout mice (PKO), and E- and P-selectin gene-interrupted mice (EPKO). Additional groups were used to evaluate the ability of a P-sel antagonist (rPSGL-Ig) and an antibody directed against PSGL-1 to downregulate the effects of P-sel in CT mice and WT mice administered soluble P-sel at time of thrombosis. Animals were sacrificed on days 2 and 6 after IVC ligation. Thrombus mass (TM), vein wall morphometrics, and serum leukocyte/platelet microparticles (MPs) were evaluated by means of double-stained fluorescence-activated cell scanning analysis, and soluble P- and E-sel protein determination by ELISA. RESULTS: At days 2 and 6 in phase I of the experiment, significant differences (P <.01) in TM were noted between groups, with CT animals having the largest thrombi (50% and 57% increase in TM compared to WT at days 2 and 6) while EPKO mice had the smallest thrombi. Statistically, greater levels of neutrophils and total inflammatory cells were noted in the vein walls of CT animals at day 2 compared with WT and PKO animals. A significant difference was noted between CT and EPKO for neutrophils, monocytes, and total inflammatory cells, also at day 2. At day 6, the only statistically significant difference was found for monocytes, with a higher number in the CT animals than in WT animals. The evaluation of MPs revealed that the CT mice had a mixed leukocyte (MAC-1) and platelet (CD41) MP population that was also present in WT and PKO mice on day 2 and day 6. EPKO mice revealed a primarily platelet-derived MP population. Of interest, the CT mice with the highest TM showed a high amount of mean channel fluorescence for MAC-1 (phycoerythrin) antibody, indicative of leukocyte MPs. CT mice revealed statistically higher levels of soluble P-selectin at days 2 and 6. In phase 2, an antibody directed against PSGL-1 was more effective than rPSGL-Ig in decreasing TM and limiting leukocyte-derived MP fluorescence. CONCLUSIONS: This study demonstrates that high circulating levels of P-selectin are associated with increased thrombosis, whereas a lack of P-selectin and E-selectin is associated with a lessening of thrombosis. Additionally, leukocyte MPs are associated with venous thrombus formation. These data suggest the importance of selectins to venous thrombogenesis and show that P-selectin and leukocyte-derived MPs should be good targets to limit venous thrombus formation.     

Renal tubular epithelial cell apoptosis by Fas-FasL-dependent self-injury can augment renal allograft injury

The role of Fas-FasL interactions in kidney allograft injury may be complex as renal tubular epithelial cells (TEC) express both Fas and FasL. The role and regulation of TEC self-injury has not been investigated. In co-cultures of TEC, FasL-bearing, Fas-null TEC was demonstrated to induce apoptosis of TEC-bearing Fas. Co-culturing effector lpr-TEC (M3.1-lpr) with target WT-TEC (CS3.7) at a ratio of 10:1 (E/T) induced 15.2 +/- 2.4% of target apoptosis as compared to its basal level of 2.6 +/- 0.3%. Similarly lpr-TEC induced apoptosis in gld-TEC (MRM-gld) from a basal level of 3.7 +/- 0.2% to 6.4 +/- 0.3%. Expression of kidney Fas-FasL on injury was tested in a renal transplant model. C57BL/6 (B6) mice were transplanted with Fas-deficient C3H-lpr/lpr or FasL mutation C3H-gld/gld kidneys as compared to normal (wild-type [WT]) C3H/Hej donors. Survival of both lpr and gld recipient was improved compared to WT donors (P <.05) as was function of lpr and gld kidneys indicated by a lower serum creatinine (LPR: 41 +/- 8 micromol/L; GLD: 52 +/- 7 micromol/L) as compared to the WT donors (84 +/- 8 micromol/L, P <.001). These results demonstrate that activated TEC may commit a novel and previously unreported form of self-injury (fractricide) through Fas-FasL. These results suggest that inhibition of renal Fas or FasL might be a useful strategy to prevent TEC loss during rejection.     

Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice

BACKGROUND: The norepinephrine (NE) analog phenylephrine has previously been shown to induce atypical prostate hyperplasia in rats. The objective of the present study was to provide further insight into the mechanism of phenylephrine-induced prostate growth. METHODS: Adult male C57/BL6 mice were given daily subcutaneous injection of phenylephrine, isoproterenol, or phenylephrine in combination with BMY7378, cyclazosin, RS100329, or yohimbine, and the effects on ventral prostate histology, and proliferative and apoptotic indices determined. Phenylephrine was also administered in combination with testosterone in castrated mice. RESULTS: Atypical prostatic hyperplasia characterized by piling up and/or papillary infolding of epithelial cells with concomitant stromal smooth muscle hyperplasia was seen in adult mice given subcutaneous injection of phenylephrine daily for 26 days. Phenylephrine induced hyperplasia was more severe proximally and was associated with significantly reduced rates of apoptosis (but no change in cell proliferation) in both stromal and epithelial compartments. Only the alpha(1A)-adrenoceptor selective subtype antagonist RS100329 abrogated the phenylephrine-induced hyperplasia. Using selective antibodies, the alpha(1A-1)-adrenoceptor subtype was predominantly localized to the stromal compartments of the mouse and rat ventral prostates. The effects of phenylephrine were mediated independent of testicular androgens. CONCLUSIONS: Prostatic hyperplasia in mice occurs as a consequence of subchronic administration of the sympathomimetic phenylephrine. Response to phenylephrine is mediated by the alpha(1A)-adrenoceptor, which predominates in the stroma of the rodent ventral prostate. Conceivably, therefore, phenylephrine could directly modulate prostate stromal growth, and indirectly modulate epithelial growth in a paracrine fashion. We cannot, however, rule out the contribution of other indirect effects such as hypoxia/reperfusion or effects on intermediary metabolism.     

白介素6基因敲除小鼠肝脏移植后的肝脏再生研究

目的 观察白介素6基因敲除(interleukin 6 knockout,IL-6 KO)小鼠原位肝移植后存活时间和肝脏再生的情况. 方法建立正常小鼠(C57BL/6 wild type,C57BL/6WT)和IL-6 KO小鼠的肝移植模型.38只小鼠分为3组:C57BL/6 WT→C57BL/6 WT肝脏移植对照组(n=10),IL-6 KO→IL-6 KO肝脏移植组(n=14)和IL-6 KO→C57BL/6 WT肝脏移植组(n=14).移植后观察小鼠肝移植物的存活情况.溴脱氧尿核苷(bromodeoxyuridine,BrdU)免疫组化检测移植肝脏的再生.结果 实验各组肝移植物的冷缺血时间均＜1 h.对照组小鼠肝移植后存活时间＞16 d.IL-6 K0→IL-6 KO组的肝移植后移植物不能存活(2 d).IL-6 KO→C57BL/6 WT组的肝移植后移植物不能存活(1.6 d).实验各组间存活时间比较,差异有统计学意义(F=190.09,P＜0.01).对照组小鼠肝脏移植后组织学检查证实肝脏组织损伤较轻,无组织坏死等改变.肝脏移植术后48 h BrdU摄取轻度增加.IL-6 KO小鼠肝移植后,组织学检查表现出片状坏死和肝细胞气球样变等改变.肝移植术后48 h免疫组化发现有极少数BrdU摄取.结论 IL-6 KO小鼠的肝移植后肝再生反应障碍,肝移植物不能存活.IL-6是肝脏再生反应中一个重要因子.     

Correlated biochemical and stereological studies on testosterone metabolism in the stromal and epithelial compartment of human benign prostatic hyperplasia

The growth and function of the human prostate is dependent upon a continuous supply of androgens, mainly 5 alpha-dihydrotestosterone, the 5 alpha-reduced metabolite of testosterone. Within the human prostate dihydrotestosterone is thought to be the intracellular mediator of androgen action. Although it is well documented that dihydrotestosterone is evenly distributed between the stromal and epithelial compartment of the prostate, the anatomical localization of dihydrotestosterone formation within the normal and hyperplastic prostate is still not established. To provide further insight into this problem we have measured, under conditions approximating the in vivo state, dihydrotestosterone formation in prostates obtained from 4 men with normal prostates and 36 men with benign prostatic hyperplasia. In addition to this we have performed histometric analysis of the cellular composition of the samples incubated, in order to correlate the morphological and the histochemical findings. Dihydrotestosterone is the major metabolite, and androstanediol and androstenedione were formed in smaller quantities. Under the given conditions metabolite formation from testosterone increased linearly for 60 minutes and the half maximum rate of dihydrotestosterone formation (Km) was observed at about 1.25 X 10(-6) M testosterone, a value similar to that reported for rat prostatic nuclei and human prostatic tissue. Dihydrotestosterone formation was higher in hyperplastic prostates than in the normal prostate. (Student's t test: p less than 0.05). The stroma in both the normal and hyperplastic tissue converts testosterone to dihydrotestosterone very actively. No significant relation was found between dihydrotestosterone formation and the per cent distribution of the stromal and epithelial compartment in any sample studied. In conclusion, our results are compatible first with the thesis that the rate of dihydrotestosterone formation is increased in the hyperplastic prostate and secondly with the concept that the rate of dihydrotestosterone formation is approximately the same in the epithelial and stromal compartments of the prostate.     

A central role for CD95 (Fas) in T-cell reactivity after injury

BACKGROUND: Recent findings indicate that severe injury primes the immune system for an enhanced and lethal proinflammatory cytokine response against bacterial-derived superantigens. This study asked whether this response to injury involves the CD95 (Fas) signaling pathway. METHODS: To assess superantigen-mediated mortality, wild-type (WT) C57BL/6 and Fas-deficient C57BL/6 lpr (-/-) (lpr) mice underwent burn or sham injury and were challenged 2 hours later with staphylococcal enterotoxin B (SEB). Spleen cells from sham and burn WT or lpr mice were stimulated in vitro with SEB to assess injury effects on IL-2, TNF-alpha, and IFN-gamma production. RESULTS: Lpr burn mice survived the SEB challenge (100% survival), while WT burn mice showed a high mortality (17% survival, P < 001, analysis of variance [ANOVA]). Sham lpr or WT mice suffered no mortality to the SEB challenge. In vitro studies demonstrated that burn lpr mice produced significantly less TNF-alpha, IFN-gamma, IL-2 than burn WT mice (P <.01, ANOVA). Burn injury markedly enhanced SEB-stimulated IFN-gamma production by WT spleen cells and CD8+ T cells, while this did not occur in SEB-stimulated lpr spleen cells. CONCLUSIONS: These findings support the hypothesis that the CD95 (Fas) signaling pathway plays an integral role in the injury-induced enhanced and lethal T-cell reactivity against bacterial superantigens.     

Protective effect of Prostane in experimental prostatic hyperplasia in rats

Aim: Prostane, a polyherbal formulation, was evaluated for its efficacy on ,5a-reductase inhibition, a-adrenergie anta-gonistic activity and testosterone-induced prostatic hypeqllasia. Methods: 5a-reductase inhibition was evaluated usingrat prostate hornogeante as an enzyme source. Adrenergic antagonistic“ activity was evaluated using isolated rat vas def-erens. Experimental prostatic hyperplasia was induced in rats by“ giving testosterone 3 mg/kg sc for 21 days. Re-suits: Prostane dose-dependently inhibited 5a-reductase aetivity and exhibited a-adrenergic antagonistic activity. Treat-ment with Prostane at 250, 500 and 750 mg/kg body wt, po for 21 days significantly reduced the prostatic weight, theepithelial height and the stroinal proliferation in experimental prostatic hypertrophy. Conclusion: Prostane is effectivein the treatment of experimental prostatic hypertrophy in rats and may be passed on to clinical trials on benign prostatichypertrophy after necessary toxicological evaluations. ( Asian J Androl 1999 Dec ; l : 175 - t79 )     

The effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on testicular steroidogenesis in infantile male rats

Exposure of adult male animals to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreases serum androgen concentrations. Reduction in androgen levels after maternal exposure has also been reported, but these results have not been reproduced. We have earlier shown that TCDD stimulates rather than inhibits testosterone synthesis in the prenatal rat testis. The aim of the present study was to elucidate in utero-induced effects of TCDD on testicular steroidogenesis in the 14-day-old infant rats. At that time the foetal Leydig cell population is still the prevailing source of androgens. Pregnant Sprague-Dawley dams were given a single oral dose of TCDD (0, 0.04, 0.2, or 1.0 microg/kg) on day 13 of pregnancy. On postnatal day 14, the body weight of male offspring was reduced after exposure to 1.0 microg/kg TCDD (from 33.9 +/- 1.66 g to 31.6 +/- 2.67 g). Relative testis weight, plasma testosterone, luteinizing hormone and follicle-stimulating hormone levels remained unaltered in all exposure groups. Moreover, in ex vivo incubations, testosterone and cAMP production was not affected. StAR protein level in the freshly isolated testes was increased in the 0.2 microg/kg group, and seminiferous cord diameter in the 0.04 microg/kg group. The present study confirms our earlier findings in in utero TCDD-exposed foetal testis indicating that maternal TCDD exposure does not negatively influence the developmental testosterone production of foetal type Leydig cells in rats.