Functional and morphological changes in the hypothalamo-pituitary-gonadal axis of aged female rats.

Age-related functional and morphological alterations in the hypothalamo-pituitary-gonadal axis were investigated in old recurrently pseudopregnant (RPP) female rats, and these alterations were compared with those in young diestrous rats. LHRH in the median eminence (ME) and mediobasal hypothalamus (MBH) as well as plasma FSH, LH, and progesterone were measured by RIA. LHRH in the lateral ME (LME) and pituitary FSH and LH were evaluated by morphometry and densitometrical immunocytochemistry. Furthermore, by light microscopy, we classified and counted the number of ovarian follicles and corpora lutea. LHRH concentrations in the ME and MBH were similar in old and young rats, whereas in old rats, plasma FSH was markedly increased, LH was moderately increased, and plasma progesterone was unchanged. The number and the total area and immunoreactivity of LHRH-labeled axon cross sections in the LME were reduced in old rats. The number of nucleated FSH-labeled cells and total FSH area and immunoreactivity were almost twice in old compared with young animals. The measurements of LH-labeled cells were not different between the two groups. In old rats, the numbers of ovarian follicles and corpora lutea were reduced and that of atretic follicles increased. In conclusion, age-related morphological impairments of LHRH axons associated with an increased number of FSH gonadotropes and higher plasma FSH in our old RPP rats suggest hypothalamic and pituitary disturbances, which may largely contribute to the complex hormonal disarrangement responsible for the decline of reproductive functions in old female rats.     

Endocrine and behavioral modifications in aging male rats

Endocrine and behavioral effects of age and aging have been studied in 4 groups of Sprague-Dawley male rats (2, 6, 12, 24 months old). Plasma testosterone decreases after 6 months of age, plasma estradiol decreases from 2 to 6 months, then it increases with age and decreases again with aging (from 12 to 24 months). Aromatization of testosterone in brain tissue is similar in 2-, 12- and 24-month-old rats, but at 6 months a significant increase is observed. Testosterone biosynthesized in the gonad from dehydroepiandrosterone increases from 2 to 6 months, then it decreases, while the other metabolites of dehydroepiandrosterone show an increment with age. Corticosterone and 17 alpha-hydroxyprogesterone biosynthesized in the adrenal decrease with aging. Explorative and locomotor activity decreases with age and aging, while emotionality decreases from 2 to 12 months, but it increases with aging. These results indicate that endocrine equilibrium is remarkably altered by aging process showing a decrease of plasma sexual hormones and of gonadal activity. The decrement of aromatization of testosterone in the brain, which occurs between 6 and 12 months, is correlated with the decrement of plasma testosterone. It could be hypothesized that the hormones of the brain-pituitary-gonad axis are involved in the control of explorative behavior or that both hormonal and behavioral parameters are controlled by a common factor.     

Ultrastructural modifications of frog urinary bladder epithelium under the influence of hypertonic media

Summary The frog urinary bladder undergoes a marked increase in its water permeability when incubated in hypertonic media. Many similarities are found between this effect and the hydrosmotic action of antidiuretic hormone. The ultrastructural modifications of the epithelium observed under the influence of serosal hypertonicity (the intercellular spaces are dilated while the tight junctions remain closed) lead us to assume that the pathways of water movement across the epithelium could be the same in this case and in hydrosmotic response to the hormone. In contrast, when the mucosal medium is made hypertonic, the ultrastructure is differently altered: the intercellular spaces are closed, the tight junctions show small vesicles and numerous large vacuoles appearing in the cytoplasm.     

Urinary kallikrein excretion in normotensive aging female rats

The effect of aging on the intrarenal kallikrein-kinin system activity was investigated in normotensive 3-, 10-, 20-, and 30-month-old female Wistar rats. Urinary kallikrein excretion was measured by three independent assays (immunoreactive concentration, kininogenase, and amidolytic activities) and was found to decrease progressively from 10 to 30 months. In the 30-month-old rats the urinary immunoreactive kallikrein excretion represented 40-44% of the level detected in 3-month-old rats. Active and total kallikrein exhibited the same magnitude of reduction. Furthermore, the active to inactive kallikrein ratio remained unchanged throughout the life period studied. The level of urinary kallikrein inhibitor was studied by measuring the recovery of purified rat urinary kallikrein added in the samples; no change was observed with aging. None of the factors known at present to influence kallikrein excretion could be evoked to explain this age-related decrease. It is therefore suggested that this decrease may reflect a progressive impairment of the intrarenal endocrine function or an alteration in the secretion of the enzyme.     

Effects of estrogen on age-related changes in muscarinic responsiveness of the urinary bladder and lumbosacral dorsal root ganglion cells in female rats

Silymarin is a naturally available bioflavonoid and is a strong antioxidant with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated whether dietary supplementation of silymarin has any role in lipid components, lipid-metabolizing enzymes, free fatty acid profile, and expression of cyclooxygenase-2 (COX-2) in N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in rats. NDEA-induced rats showed severe hyperlipidemia along with upregulated expression of COX-2 as revealed by western blotting and immunohistochemistry. Dietary silymarin supplementation attenuated this hyperlipidemia and downregulated the expression of COX-2. Thus we conclude that compounds like silymarin with potent hypolipidemic effect are strong candidates as chemopreventive agents for the treatment of liver cancer.     

Diet-induced nephrocalcinosis and urinary excretion of albumin in female rats

This study was carried out to test the hypothesis that diet-induced nephrocalcinosis causes enhanced loss of albumin in urine, irrespective of the composition of the nephrocalcinogenic diet. Female rats were fed various purified diets for 28 days. There was a control diet (0.5% Ca, 0.04% Mg, 0.4% P, 15.1% protein, wt/wt), a low Mg (0.01% Mg), a high protein (30.2% protein) and a high P diet (0.6% P). The low Mg and high P diet induced nephrocalcinosis as demonstrated histologically and by markedly increased concentrations of kidney Ca. In rats fed the high protein diet, nephrocalcinosis was essentially absent. Group mean values of urinary excretion of albumin and plasma concentrations of urea were increased in rats fed either the low Mg or high P diet. The high protein diet did not affect urinary albumin but caused lysozymuria which was not seen in the other groups. Plasma urea was increased in rats fed the high protein diet. In individual rats, the concentration of Ca in kidney and urinary albumin excretion were positively correlated. It is suggested that nephrocalcinosis in female rats induced by either low Mg or high P intake causes kidney damage which in turn leads to increased concentrations of albumin in urine and urea in plasma.     

Intrinsic innervation of the urinary bladder of kangaroo and albino rats.

A comparative study of the intrinsic innervation in desert rodents (kangaroo rats) and others (albino rats) was carried out in an attempt to understand the functional anatomy of the bladder in these animals which are known to sustain severe water restraint. The bladder of the albino rat was innervated by predominantly thin nerves, more numerous beaded endings and few ganglia. That of the kangaroo rat had more numerous thick nerves (pre-ganglionic), large verve trunks, and ganglia which were extensively distributed in the wall. These findings indicate that the bladder of the albino rat depends mainly on the intrinsic innervation and facilatory micturition reflexes, while that of the kangaroo rat is intrinsically regulated, depending on a short neuron system. It was concluded that all the structural differences found might be essential for constant urine retention.     

Functional polymorphisms in the IL6 gene promoter and the risk of urinary bladder cancer in India

BackgroundInterleukin-6 is a multifunctional cytokine, which plays a key role in tumor proliferation and differentiation. Variations in its gene (IL6) sequence may affect the risk of developing various cancers, including urinary bladder cancer. The present study was done to find the association of functional polymorphisms in the IL6 promoter with urinary bladder cancer.Materials and methodsSingle nucleotide polymorphisms were genotyped in histologically confirmed 232 cases of urinary bladder cancer and 250 healthy controls. The controls subjects were matched to the cases by age, sex, and ethnicity. Genotyping of the polymorphisms (−174G>C; −572G>C, −596A>G) was undertaken by direct DNA sequencing. The level of association between the genotypes and urinary bladder cancer risk was estimated by odds ratios and 95% confidence intervals generated by applying the chi-square test. Linkage disequilibrium (LD) between SNPs and haplotype analysis were performed using Haploview software.ResultSignificantly higher number of smokers (p = 0.047), tobacco chewers (p = <0.001) and those with non-vegetarian food habits (p = 0.016) were seen in the case group. The distribution of genotypes at −174G>C locus differed significantly between cases and controls and the variant genotypes GC + CC were significantly rarer in the cases (p = 0.00073; OR = 0.52 95% CI 0.35–0.75). Variant genotypes (GC + CC) were more common in grade I than grade III tumors (p = 0.032), further suggesting a protective effect. No LD was found between the SNPs; however, the frequency of haplotype AGC was significantly lesser in the cases than controls (p = 0.0103), suggesting a protective effect. Genotype distribution at the other two loci (−572G>C and −596A>G) did not show association with bladder cancer.ConclusionsIL6 (−174G>C) substitution confers significant protection against the risk of urinary bladder cancer in the study population, while other substitutions in this gene (−572G>C and −596A>G) do not affect the risk. In general, there is a lack of studies on the cytokine gene polymorphisms in urinary bladder cancer.     

Relation of parity and estrous cyclicity to the biology of pregnancy in aging female rats

In the female rat, the incidence of regular estrous cyclicity and fertility decreases progressively during aging, and the causes for these are unknown. To reveal the biology of pregnancy in aging rats, we performed a longitudinal study in a colony of multiparous rats bred every 2 mo. Beginning at 4 mo and continuing to 12 mo of age in these same individual females, we determined the chronological changes in estrous cyclicity, examined the relationship between the estrous cycle pattern and fertility, and recorded the numbers of live and dead pups delivered at term. In separate groups of 4- to 12-mo-old multiparous rats, we counted the number of ova present in the oviducts (ovulation rate) one day after mating and the number of grossly normal blastocysts found in the uteri on Day 5 of pregnancy. Similar studies were also performed in primiparous rats of 8, 10, and 12 mo of age. The cessation of regular cyclicity during aging occurred significantly (p less than 0.01) earlier in virgin than multiparous rats. Fertility followed a similar but more dramatic pattern of decline than did the incidence of regular cyclicity in both the multiparous and virgin females. Few irregularly cyclic and persistent-estrous females had fertile gestations after mating, and increasing proportions of regularly cyclic females also failed to reproduce successfully at middle age (8-12 mo). Thus, regular ovulatory cycles were essential but not sufficient for fertile gestations in aging rats. Beginning at 6 mo of age, the litter sizes of multiparous rats decreased progressively, and these decreases were associated with a similar decline in the number of live but not dead pups delivered. Also, the percentage of dead pups/total number of pups delivered increased steadily during aging in multiparous (from 14% to 69%) but not primiparous females. The litter sizes of 8- to 10-mo-old primiparous females were not different from those of multiparous rats. However, the litter sizes of irregularly cyclic rats were consistently smaller than those of regularly cyclic females. Thus, parity had little effect on fecundity in aging females, whereas the cessation of regular ovulatory cycles during aging greatly decreased both the incidence of fertility and the litter size.(ABSTRACT TRUNCATED AT 400 WORDS)     

Expression of cyclooxygenase-2 in urinary bladder in rats with cyclophosphamide-induced cystitis

These studies examined the expression of cyclooxygenase-2 (COX-2) expression in the urothelium and suburothelial space and detrusor from rats treated with cyclophosphamide (CYP) to induce acute (4 h), intermediate (48 h), or chronic (10-day) cystitis. Western blot analysis and immunohistochemistry were used to demonstrate COX-2 expression. In whole mount preparations of urinary bladder, nerve fibers in the suburothelial plexus, and inflammatory cell infiltrates were characterized for COX-2 expression after CYP-induced cystitis. COX-2 expression significantly (P 相似文献   

The systematic histologic elaboration of urinary bladders with different pathologic findings (urinary bladder carcinoma, tumor-free aging urinary bladders)

We report our systematic histological examinations of 16 urinary bladders (11 bladders with cancer, 5 bladders was tumour-free). All residual tumour-free portions in bladder with multiple or solitary cancers demonstrated various precancerous variations of urothelium, not only near the tumours. In 1 urinary bladder among 5 from elder patients, we diagnosed a clinically undetected cancer. In a few cases, we correlated histological examinations with graphical demonstration (through a computer) of the exophytic tumour portions. Our results agree with individual therapy of urinary bladder cancer.     

大鼠膀胱及其牵涉区的初级传入神经起源

目的：在确定大鼠膀胱痛牵涉区的基础上,明确膀胱及其牵涉区的初级传入神经的起源。方法：经静脉注入Evans Blne,观察染料渗出和皮肤部位;将CB－HRP分别注入膀胱壁内或牵拉区皮下,观察和计数阳性标记细胞出现的部位及数目。结果：深蓝色的染料渗漏斑仅出现在耻骨联合附近皮区,膀胱的CB－HRP阳性标记神经元胞体主要集中在L－L3和L6、S1节段背根神经节（DRG）中,牵涉区的则主要分布在L2、L3节段DRG。结论：大鼠的膀胱痛牵涉区主要位于耻骨联合附近的皮肤,膀胱的初级传入神经起源广泛,而牵涉区的初级传入神经起源局限,二者在L2、L3节段DRG有一定的重叠分布。     

Phosphorylation of extracellular signal-regulated kinases in urinary bladder in rats with cyclophosphamide-induced cystitis

Phosphorylated ERK expression has been demonstrated in the central and peripheral nervous system after various stimuli, including visceral stimulation. Changes in the activation (i.e., phosphorylation) of extracellular signal-regulated kinases (pERK) were examined in the urinary bladder after 4 h (acute), 48 h (intermediate), or chronic (10 day) cyclophosphamide (CYP) treatment. CYP-induced cystitis significantly (P < or = 0.01) increased pERK expression in the urinary bladder with intermediate (48 h) and chronic CYP treatment. Immunohistochemistry for pERK immunoreactivity revealed little pERK-IR in control or acute (4 h) CYP-treated rat urinary bladders. However, pERK expression was significantly (P < or = 0.01) upregulated in the urothelium after 48 h or chronic CYP treatment. Whole mount preparations of urothelium/lamina propria or detrusor smooth muscle from control (noninflamed) rats showed no pERK-IR in PGP9.5-labeled nerve fibers in the suburothelial plexus. However, with CYP-treatment (48 h, chronic), a few pERK-IR nerve fibers in the suburothelial plexus of whole mount preparations of bladder and at the serosal edge of urinary bladder sections were observed. pERK-IR cells expressing the CD86 antigen were also observed in urinary bladder from CYP-treated rats (48 h, chronic). Treatment with the upstream inhibitor of ERK phosphorylation, U0126, significantly (P < or= 0.01) increased bladder capacity in CYP-treated rats (48 h). These studies suggest that therapies targeted at pERK pathways may improve urinary bladder function in CYP-treated rats.     

Functional consequences of histone modifications

Covalent modifications of the histone proteins have well-known roles in gene expression. Experiments reported during the past year have extended this paradigm to include roles for histone acetylation and phosphorylation in DNA double-strand break repair. In addition, new results now provide a definitive example of an acetylation histone code, whereas others reveal the workings of a charge patch mechanism. Finally, exciting research has identified new modifications, complex modification cascades, and functional links to DNA methylation and RNA interference pathways.