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1.
D K Lee  C E Bird  A F Clark 《Steroids》1975,26(1):137-147
The metabolism of testosterone (T) was studied in normal adult male rats using a constant infusion of trace amounts of the 3H-steroid into a tail vein for 3 h in order to attain a state of equilibrium. Samples of plasma, liver, kidney, prostate, seminal vesicles and muscle were analysed for 3H-testosterone, 3H-5alpha-dihydrotestosterone (5alphaDHT) and 3H-5alpha-androstanediol (Adiol). When compared to the 3H-T level in plasma there were high levels of 3H-T in kidney and of 3H-5alphaDHT in prostate and seminal vesicles. Intraperitoneal estradiol valerate administration (100 mug/day) for 4 days decreased and 3H-5alphaDHT levels in the prostate and seminal vesicles. The estrogen administration increased the T metabolic clearance rate from 17.5 1/24 h/100 g body wt to 22.6 1/24 h/100 g body wt.  相似文献   

2.
The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.  相似文献   

3.
1. Castration of adult rats markedly decreases the amounts of polyamines (putrescine, spermidine and spermine) and of RNA and DNA in the ventral prostate and the seminal vesicle. 2. Daily injections of testosterone propionate to rats castrated 7 days previously increase polyamine and nucleic acid contents more rapidly in the seminal vesicle than in the ventral prostate. 3. After 7 days of androgen treatment, polyamine and nucleic acid contents of the seminal vesicle are significantly higher than those of intact animals. Nucleic acid, but not polyamine, contents return to normal values during the next 4 days of continued treatment. In the prostate, androgen treatment increases polyamine and nucleic acid contents to, but not above, normal values. 4. Repeated doses of alpha-difluoromethylornithine, a potent enzyme-activated irreversible inhibitor of ornithine decarboxylase, totally blocked the testosterone-induced increase of putrescine and spermidine in the ventral prostate and of putrescine in the seminal vesicle. They slowed significantly the accumulation of spermine in the ventral prostate and of spermidine in the seminal vesicle. alpha-Difluoromethylornithine also retarded the testosterone-induced accumulation of RNA in the ventral prostate. However, no clear correlation was apparent between accumulation of polyamines and of nucleic acids in the two organs. 5. alpha-Difluoromethylornithine markedly slows the testosterone-induced weight gain of the prostate, but not of the seminal vesicle. Cytological studies suggest that this effect on the prostate is due to inhibition of the androgen-induced restoration of the secretion content of prostatic acini.  相似文献   

4.
L W DeLap  S Tate  A Meister 《Life sciences》1975,16(5):691-704
γ-Glutamyl transpeptidase was prepared from rat seminal vesicles by two methods and was found to be similar to rat kidney γ-glutamyl transpeptidase with respect to substrate specificity, stimulation of “glutaminase” activity by maleate, and apparent molecular weight. Histochemical studies demonstrated that γ-glutamyl transpeptidase is concentrated in the secretory epithelium of the seminal vesicle. Like the epithelium itself, the enzyme responds to the presence or absence of testosterone. The content and specific activities of γ-glutamyl transpeptidase and γ-glutamyl cyclotransferase in rat seminal vesicles are low in orchidectomized animals, an effect which is reversed by administration of testosterone but accentuated by estradiol administration. These enzymes may be involved in the secretory functions of the seminal vesicles.  相似文献   

5.
The antiandrogenic effect of levorin on immature castrated rats treated with exogenic testosterone was studied. In a dose of 200 mg/kg levorin lowered the cholesterin blood levels in the rats, inhibited the testosterone-induced increase in RNA concentration in the ventral and dorsal prostate and the seminal vesicles and to a less extent suppressed the growth of the accessory sexual glands. However, the antiandrogenic effect was observed with the use of levorin in the dose producing a pronounced toxic action evident from death of a part of the animals and a marked decrease in the animal body weight. This fact casts doubt on specificity of the levorin effect. Apparently, in high doses levorin impairs metabolism as a whole which cannot but affect the response of the sexual glands to administration of testosterone.  相似文献   

6.
1. The effects of injecting nicotinamide, 5-methylnicotinamide, ethionine, nicotinamide+5-methylnicotinamide and nicotinamide+ethionine on concentrations in rat liver of NAD, NADP and ATP were investigated up to 5hr. after injection. 2. Nicotinamide induced three- to four-fold increases in hepatic NAD concentration even in the presence of 5-methylnicotinamide or ethionine, whereas 5-methylnicotinamide or ethionine alone did not cause marked changes in hepatic NAD concentration. 3. Nicotinamide alone also induced a twofold increase in hepatic NADP concentration. However, in the presence of 5-methylnicotinamide+nicotinamide, the NADP concentration decreased by 25% after 5hr., and in the presence of nicotinamide+ethionine by 30% in the same time. In the presence of 5-methylnicotinamide or ethionine alone hepatic NADP concentrations fell by 50% after 5hr. 4. 5-Methylnicotinamide inhibited the microsomal NAD(+) glycohydrolase (EC 3.2.2.6) by 60% at a concentration of 1mm and the NADP(+) glycohydrolase by 40% at the same concentration. 5. The rat liver NAD(+) kinase (EC 2.7.1.23) was found to have V(max.) 4.83mumoles/g. wet wt./hr. and K(m) (NAD(+)) 5.8mm. This enzyme was also inhibited by 5-methylnicotinamide in a ;mixed' fashion. 6. The results are discussed with respect to the control of NAD synthesis. It is suggested that in vivo the NAD(P)(+) glycohydrolases are effectively inactive and that the increased NAD concentrations induced by nicotinamide are due to increased substrate concentration available to both the nicotinamide and nicotinic acid pathways of NAD formation.  相似文献   

7.
1. The ability of exogenously administered cyclic AMP (adenosine 3':5'-monophosphate) to exert andromimetic action on certain carbohydrate-metabolizing enzymes was investigated in the rat prostate gland and seminal vesicles. 2. Cyclic AMP, when injected concurrently with theophylline, produced marked increases in hexokinase, phosphofructokinase, glyceraldehyde phosphate dehydrogenase, pyruvate kinase, and two hexose monophosphate-shunt enzymes, as well as alpha-glycerophosphate dehydrogenase activity in accessory sexual tissues of castrated rats. The 6-N,2'-O-dibutyryl analogue of cyclic AMP caused increases of enzyme activity that were greater than those induced by the parent compound. 3. Time-course studies demonstrated that, whereas significant increases in the activities of most enzymes occurred within 4h after the injection of cyclic AMP, maximal increases were attained at 16-24h. 4. Increase in the activity of the various prostatic and vesicular enzymes was dependent on the dose of cyclic AMP; in most instances, 2.5mg of the cyclic nucleotide/rat was sufficient to elicit a statistically significant response. 5. Administration of cyclic AMP and theophylline also produced stimulation of enzyme activities in secondary sexual tissues of immature rats. 6. Cyclic AMP and theophylline did not affect significantly any of the enzymes studied in hepatic tissue. 7. Stimulation of various carbohydrate-metabolizing enzymes in the prostate gland and seminal vesicles by cyclic AMP was independent of adrenal function. 8. Concurrent treatment with actinomycin or cycloheximide prevented the cyclic AMP- and theophylline-induced increases in enzyme activities in both castrated and adrenalectomized-castrated animals. 9. Administration of a single dose of testosterone propionate (5.0mg/100g) to castrated rats caused a significant increase in cyclic AMP concentration in both accessory sexual tissues. 10. In addition, treatment with theophylline potentiated the effects of a submaximal dose of testosterone (1.0mg/100g) on all those prostatic and seminal-vesicular enzymes that are increased by exogenous cyclic AMP. 11. The evidence indicates that cyclic AMP may be involved in triggering the known metabolic actions of androgens on secondary sexual tissues of the rat.  相似文献   

8.
Intraperitoneal administrations of testosterone (0.5 microgram/g body wt), and ovine LH (1.0 microgram/g body wt), GH (5 micrograms/g body wt) and prolactin (10 micrograms/g body wt) daily for 7 days during early prespawning phase (May) in C. batrachus produced varied effects on seminal vesicle (SVSI) and testicular (GSI) weights and biochemical correlates. Testosterone and LH treatments significantly increased serum testosterone level and concentrations of total proteins, fructose, hexosamines and sialic acid in both seminal vesicles and testis. Serum E2 levels increased significantly only after testosterone treatment. GH treatment increased significantly serum testosterone level and only the concentrations of SV hexosamines and testicular protein. Prolactin, however, significantly lowered serum testosterone level and concentrations of total protein, hexosamines in both SV and testis, and testicular fructose and sialic acid levels. The results show that the stimulating effect of LH and GH on SV and testicular activity is mediated through the increased secretion of testosterone and the inhibitory effect of prolactin by decreased testosterone secretion.  相似文献   

9.
Steroidal (cyproterone acetate) and non-steroidal (RU23908 and hydroxyflutamide) antiandrogens are able to block testosterone-induced increases in nuclear androgen receptor (AR) in the prostate of 1-day orchidectomized rats, but when given alone, RU23908 and hydroxyflutamide increase nuclear AR (RU23908 greater than hydroxyflutamide) in the same animal model. The increases in nuclear AR induced by antiandrogen alone or with testosterone alone are blocked by cycloheximide 1 h after administration, suggesting that androgen or antiandrogens induce de novo AR synthesis. Concomitant to nuclear AR accumulation, testosterone is able to induce depletion of cytosol and microsomal AR. Blockade of testosterone-induced depletion of microsomal AR, but not of cytosol AR, occurs in the presence of antiandrogens. Cyproterone acetate has a higher relative binding affinity (RBA) for microsomal AR and cytosol AR than RU23908 or hydroxyflutamide. This phenomenon is in good agreement with the degree of inhibition by these compounds of the association rate of androgen for the microsomal AR. This correlation between RBA and inhibition of the initial rate of hormone binding to the receptor is not found for cytosol AR. The results show that antiandrogens are not 'pure' antagonists of androgen action and they are potent agonists in the absence of testosterone. Furthermore, testosterone alone or antiandrogens per se regulate AR levels acutely by protein-synthesis dependent mechanisms of action, in rat ventral prostate.  相似文献   

10.
Glucocorticoids and aspirin antagonize the androgenic response in mouse kidney, but not in ventral prostate or seminal vesicles. These agents impeded the testosterone-mediated increase in kidney weight, cytochrome c oxidase, and lysosomal hydrolases and urinary excretion of lysosomal hydrolases and proteins. They also attenuated the testosterone-induced decrease in enzyme latency and membrane stability of kidney lysosomes. In contrast, the antiandrogen cyproterone acetate is weakly androgenic in kidney and potentiates testosterone-induced lysosomal enzymuria and proteinuria (synandrogenic effect).  相似文献   

11.
Intact Wistar male rats injected on Day 1 with 500 micrograms of estradiol benzoate or olive oil were decapitated on Days 15 and 22 or maintained until adulthood to analyze the balanopreputial separation. Other oil or estradiol-treated rats were orchidectomized on Day 15 and decapitated on Day 22. The neonatal estrogenization produced the following reproductive changes prior to puberty: testis, adrenal, and ventral prostate atrophy; increase in the weights of seminal vesicles and epididymis; decrease in testosterone plasma levels; delayed balanopreputial separation; abolition of luteinizing hormone response to orchidectomy; transient increase in prolactin plasma levels; and blockade in seminal and prostate response to orchidectomy.  相似文献   

12.
1. The rates of decomposition of methyl methanesulphonate, dimethyl sulphate and N-methyl-N-nitrosourea in the rat were measured. 2. Dimethyl sulphate is no longer detectable in the blood of the rat 3min. after an intravenous dose (75mg./kg. body wt.). Methyl methanesulphonate is only just detectable in the blood 1(1/2)hr. after an intravenous dose (100mg./kg. body wt.). N-Methyl-N-nitrosourea is no longer detectable in the blood 15min. after an intravenous dose (100mg./kg. body wt.). 3. The exhalation of (14)CO(2) after an intragastric dose of N[(14)C]-methyl-N-nitrosourea (100mg./kg. body wt.) is appreciably slower than after an intravenous dose, from which it is estimated that the lifetime in the rat is 2-3hr.  相似文献   

13.
Suckling rats were injected subcutaneously with doses of L-ethionine (0.1 mumole/g body wt) at intervals of 12 hr. In the latter group, phenylalanine hydroxylase was effectively inhibited in vivo resulting in hyperphenylalaninemia and phenylketonuria. Due to the well-known sex-specific differences in L-ethionine metabolism female rats were much more affected by chronic administration of L-ethionine. The underlying mechanism of enzyme inhibition by ethionine could be disturbed protein synthesis and impaired protein phosphorylation, which was suggested by pronounced decreases in ATP content in liver. In the high dosage group depletions mainly of the branched-chain amino acids and lysine occurred in serum and brain, whereas the concentrations of methionine and tryptophan were increased. Tyrosine tended to be decreased in the course of hyperphenylalaninemia. Hyperphenylalaninemia and other resulting amino acid imbalances obviously impaired brain development during the early postnatal period. Concomitantly with reductions in protein concentrations, the activity of cathepsin D, a major intralysosomal acid proteinase, was increased in brain, suggesting also higher protein catabolism in brain. Side effects of this treatment, however, were higher mortality, loss of body weight, and a general impression of delayed development, resembling a state of undernutrition to some extent. These obvious side effects of ethionine limit the usefulness of ethionine as a suitable model for classic phenylketonuria in suckling rats.  相似文献   

14.
The hypoglycemic effect of Bordetella pertussis (Challenge strain No.18323) purified cell extract (protein with traces of carbohydrates, 2 mg%) administered (0.1 mg/100 g body wt. i.v.) into mice on the activities of the key regulatory enzymes, viz. glucokinase, phosphofructokinase, pyruvate kinase, glyceraldehyde phosphodehydrogenase, glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase, of glycolytic pathway in liver has been studied at varying intervals after injection. The maximum hypoglycaemic effect was observed at the end of 12 hr, while activities of all the enzymes studied showed significant enhancement after 18 hr, thus suggesting increased glucose utilization towards the formation of pyruvate. Actinomycin D is found to inhibit stimulation of G-6-PD activity in B. pertussis treated animals, thereby indicating the role of B. pertussis in synthesis of this enzyme.  相似文献   

15.
Oxidative stress is a key step in the pathogenesis of ethanol associated liver injury. Ethanol administration induces an increase in lipid peroxidation either by enhancing the production of oxygen reactive species or by decreasing the level of endogenous antioxidants. In this present study, four groups of male guinea pigs (Cavia porcellus) were maintained for 45 days as follows: Control group (1 mg ascorbic acid (AA)/100 g body wt./day); Ethanol group (1 mg AA/100 g body wt./day+900 mg ethanol/100 g body wt./day); Selenium+AA group (25 mg AA+0.05 mg sodium selenite/100 g body wt./day); Ethanol+Se+AA group (25 mg AA+0.05 mg sodium selenite/100 g body wt.+900 mg ethanol/100 g body wt./day). Malondialehyde (MDA), hydroperoxides (HP) and conjugated dienes (CD) were significantly increased, while the activities of scavenging enzymes superoxide dismutase (SOD) and catalase were reduced in the alcohol administered groups. Co-administration of Se+AA along with alcohol increased the activities of scavenging enzymes and reduced the lipid peroxidation products level in hepatic tissues of guinea pigs. Activities of glutathione peroxidase (GPX) and glutathione reductase (GR) were enhanced in co-administered group. gamma-Glutamyl transpeptidase (GGT), a marker enzyme of alcohol induced toxicity, was also reduced, as was the glutathione content. This study suggests that the combined effect of Se+AA, provides protection against alcohol-induced oxidative stress as evidenced from the decreased levels of lipid peroxidation products and enhanced activities of scavenging enzymes.  相似文献   

16.
N Szymik  B Buntner 《Endokrinologie》1975,64(3):304-310
In 31 adult rats of Wistar strain (body weight 231 +/- 14g) the relationships between testosterone concentration in testicular venous blood of an individual rat and weight of accessory sex organs (testes, seminal vesicles, ventral prostate, levator ani muscle) and citric acid and fructose concentrations in seminal vesicles were investigated. No direct relationship was found between testosterone concentration and the above parameters. The correlation coefficient varied from 0.042 to 0.394.  相似文献   

17.
Ribonucleic acid synthesis during the early action of thyroid hormones   总被引:39,自引:15,他引:24       下载免费PDF全文
1. The effect on RNA synthesis in rat liver of thyroidectomy and the administration of thyroid hormone, especially during its physiological latent period, was studied by determining: (a) the activity of DNA-dependent RNA polymerase in isolated nuclei; (b) the rate of synthesis of nuclear and cytoplasmic RNA in vivo; (c) polyribosomal sedimentation profiles; (d) the response of microsomes and ribonucleoprotein particles to polyuridylic acid; (e) the effect of inhibitors of RNA and protein synthesis on the biological activity of hormones. 2. The DNA-dependent RNA-polymerase activity of isolated rat-liver nuclei was lowered by thyroidectomy and stimulated by the administration of tri-iodo-l-thyronine or l-thyroxine (2-25mug./100g. body wt.) to both normal and thyroidectomized rats. In thyroidectomized rats, the activity of the Mg(2+)-activated RNA-polymerase reaction (for which the product is mainly ribosomal type of RNA) was stimulated at 10-12hr. after a single injection of tri-iodothyronine, reaching a peak value of 60-90% stimulation at 45hr. after hormone administration. The Mn(2+)/ammonium sulphate-activated RNA-polymerase reaction (for which the RNA product is more DNA-like) was not affected for 24hr. after hormone administration but stimulated by 30-40% at 45hr. The response of both RNA-polymerase reactions to the hormone in vivo paralleled the physiological response but the enzyme was not stimulated by the addition in vitro of the hormone to isolated nuclei. 3. Within 3-4hr. after tri-iodothyronine administration to thyroidectomized rats, the specific activity of rapidly labelled nuclear RNA, after a 10min. pulse of [6-(14)C]orotic acid, was 30-40% greater than the control values, the stimulation reaching 100 and 200% at 11 and 16hr. respectively after hormone administration. Longer exposures to [6-(14)C]orotic acid and [(32)P]phosphate showed that the hormone accelerated the synthesis of mitochondrial, microsomal (or ribosomal) and soluble RNA. The greater part of the labelled nuclear RNA was of the ribosomal type. The hormone-induced increases in the incorporation of radioactive precursors into RNA were not preceded, but followed, by enhanced uptake of the precursor. There was no change, per g. of liver, of DNA, nuclear RNA or soluble RNA, but there was a 40-60% increase in the amount of ribosomal RNA between 35 and 45hr. after a single injection of tri-iodothyronine to thyroidectomized rats. 4. Coinciding with the increase in ribosomal RNA after hormone administration was an increase in the average size and amount of polyribosomes. The newly formed ribonucleoprotein particles, or messenger RNA attached to them, or both, were more firmly bound to microsomal membranes after hormone treatment. 5. Polyuridylic acid caused a bigger stimulation of incorporation of [(14)C]phenyl-alanine by ribonucleoprotein particles, but not by microsomes, from thyroidectomized rats as compared with preparations from normal animals. The response of ribonucleoprotein particles to polyuridylic acid was lowered after tri-iodothyronine treatment of thyroidectomized rats. 6. Actinomycin D, 5-fluorouracil, puromycin and cycloheximide caused a 70-100% inhibition of the stimulatory effect of l-thyroxine and tri-iodo-l-thyronine on basal metabolic rate and growth rate in both normal and thyroidectomized animals. Administration of actinomycin D also abolished the stimulation of RNA polymerase by tri-iodothyronine. 7. It is concluded that regulation of nuclear and ribosomal RNA synthesis is an essential step leading to the biological action of thyroid hormones and that the formation of new ribosomes is an important aspect of the control of cytoplasmic protein synthesis by these hormones.  相似文献   

18.
1. The activities of l-ornithine decarboxylase (EC 4.1.1.17) and S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50) were dramatically enhanced in both the ventral prostate and the seminal vesicle of castrated rats in response to androgenic stimulation. The time course of the stimulation of ornithine decarboxylase together with the quantitatively different response of adenosylmethionine decarboxylase to testosterone treatment in the prostate gland and seminal vesicle indicated that the enhancement in polyamine synthesis in the ventral prostate may reflect both cellular proliferation and the restoration of the secretory functions of the organ. In the seminal vesicle, however, the stimulation of the polyamine-biosynthetic pathway more closely resembled the pattern found in other rat tissues, such as regenerating liver, undergoing compensatory growth. 2. Ornithine decarboxylase activity in the ventral prostate and especially in the seminal vesicle of sexually mature rat was diminished in vivo by various short-chain diamines such as 1,2-diaminoethane, 1,3-diaminopropane and putrescine (1,4-diaminobutane). These diamines had no direct effect on the enzyme activity in vitro. 3. In contrast with the marginal decrease in ornithine decarboxylase activity produced by diaminoethane in the ventral prostate of non-castrated animals, repeated injections of the latter amine completely prevented the intense stimulation of the enzyme activity in the ventral prostate and seminal vesicle of castrated rats at 24h after the commencement of testosterone treatment. 4. The decrease in ornithine decarboxylase activity observed after injections of diamines (putrescine) in the ventral prostate was apparently associated with a similar decrease in the amount of immunoreactive protein as revealed by immunotitration of the enzyme with antiserum to rat ornithine decarboxylase.  相似文献   

19.
20.
The conversion of testosterone (T) to 5alpha-dihydrotestosterone (DHT) has been demonstrated in Penicillium crustosum broth obtained from fermented pistachios, lemons and corn tortillas. Furthermore, the presence of 5alpha-reductase enzyme, which is responsible for this conversion, has been established by electrophoretical techniques in these cultures.5alpha-Reductase enzyme is also present in animal and human androgen-dependent tissues as well as in prostate and seminal vesicles. The increase of the conversion of T to DHT in prostate gland, has been related to some illnesses such as benign prostate hyperplasia and prostate cancer. Furthermore, treatment with 5alpha-reductase inhibitors such as finasteride reduces the prostate growth. These data have stimulated research for the synthesis of new molecules with antiandrogenic activity, whose biological effect needs to be demonstrated.The purpose of this study is to determine the inhibition pattern of 5alpha-reductase in P. crustosum by finasteride and the new steroidal compound PM-9. K(m) and V(max) values for T, were determined in the broths by Lineweaver-Burk plots using different testosterone concentrations. The inhibition pattern of finasteride and PM-9 was also determined by Lineweaver-Burk using different concentrations of T and inhibitors. Results show that finasteride and PM-9 inhibit 5alpha-reductase present in the broth in a competitive manner.  相似文献   

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