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1.
Aminoglutethimide (AG), an inhibitor of steroid biosynthesis, seems to have an extraglandular site of action on steroid catabolism. To study this effect, five males with peripheral hypogonadism were first given testosterone propionate and then the same dose was repeated combined with AG and urinary testosterone, and its metabolites were measured. AG was shown to have a very evident effect on the peripheral degradation of exogenous testosterone. This may be responsible for a few signs of virilization and fetal masculinization in women taking AG. 相似文献
2.
Yoichi Ichikawa Koichiro Yoshida Mitsuhiro Kawagoe Eizo Saito Yoshibumi Abe Kazumi Arikawa Mitsuo Homma 《Metabolism: clinical and experimental》1977,26(9):989-997
The radioactivities of cortisol and cortisone in plasma were determined following simultaneous injection of 14C-cortisol and 3H-cortisone. The plasma concentrations of 14C-cortisol and 3H-cortisone decreased as a first-order function of time after an initial rapid drop, while there was a prompt appearance of 14C-cortisone and 3H-cortisol in plasma, which also decreased as a first-order function. The biologic half-lives of these four isotopic steroids were essentially identical. The ratio of 14C-cortisone to 14C-cortisol and that of 3H-cortisone to 3H-cortisol in plasma were constant after 60 min following injection and were identical, which suggested that cortisol and cortisone in plasma were at dynamic equilibrium. This ratio was 0.36 ± 0.01 (SE) in normals; it was decreased in patients with hypothyroidism (0.21 ± 0.03) and inflammatory diseases (0.18 ± 0.01) and was variable in hyperthyroid patients (0.42 ± 0.11). The ratio of the metabolic clearance rate of cortisone to that of cortisol was significantly increased in hypothyroid patients and in patients with inflammatory diseases, while urinary 11-ketonic metabolites of cortisol are known to decrease relative to its 11-hydroxy metabolites in these patients. These data and the decreased cortisone-to-cortisol ratio at equilibrium were consistent with the altered equilibrium between cortisol and cortisone, favoring cortisol, in these patients. It was suggested that the altered equilibrium between these steroids may be an important factor in determining the effectiveness of secreted or exogenously administered cortisol and the plasma concentration of cortisone in several disorders. 相似文献
3.
Ami Klein Haiuta Kaufmann Shoshana Mannheimer Henry Joshua 《Metabolism: clinical and experimental》1978,27(6):731-736
A study was conducted to determine the pattern of cortisol metabolism by lymphocytes obtained from four groups of subjects: 27 male and female patients suffering from various types of malignancy other than malignancy of lymphatic tissues; and 26 healthy male and female controls. Known concentrations of cells were incubated with 1,2-3H-cortisol and the products were isolated by thin-layer and paper chromatography. Three metabolites were found to be produced by lymphocytes from both normal and cancer-bearing patients: 20α-hydroxycortisol, 20β-hydroxycortisol, and tetrahydrocortisol. Cells from the female control group were found to be more active than those from the male controls, while cells from cancer-bearing patients were markedly more active than the normal cells, regardless of sex. It is suggested that this finding of increased metabolism of cortisol by lymphocytes from patients with different types of malignancy other than lymphoma may provide the basis for a new diagnostic aid. 相似文献
4.
The in vitro effect of the addition of non-17-hydroxylated and 17-hydroxylated steroids on the production of aldosterone has been studied in the rat. The biosynthesis of deoxycorticosterone, corticosterone, and aldosterone was increased when progesterone or pregnenolone was added to the incubation media, but neither cortisol nor 11-deoxycortisol was produced. The addition of 17α-hydroxyprogesterone or 17α-hydroxypregnenolone to the incubation media resulted in the biosynthesis of cortisol and 11-deoxycortisol by the rat adrenal; concomitantly, a decrease in aldosterone production occurred. However, no decrease in aldosterone production resulted when cortisol and 11-deoxycortisol were added directly to the incubation media. These studies show that neither cortisol nor 11-deoxycortisol inhibits the in vitro biosynthesis of aldosterone and suggest that other mechanisms are involved. 相似文献
5.
Donald J. Tindall Vidar Hansson William S. McLean E.Martin Ritzen Shihadeh N. Nayfeh Frank S. French 《Molecular and cellular endocrinology》1975,3(2):83-101
The cytoplasmic receptor (CR) in rat epididymal 105,000 supernatant was separated from the androgen-binding protein (ABP) by gel electrophoresis following labeling with [1,2,6,7-3H]-testosterone in vivo. ABP disappeared from epididymal supernatants after castration 01 hypophysectomy, while CR remained unchanged. CR was evenly distributed between caput and cauda, while much more ABP was present in caput. Properties of CR in epididymis and prostate were similar and distinctly different from ABP. Binding to CR was destroyed by charcoal treatment (1 mg/mg protein) of supernatant at 0 °C for 6 h, heating at 50 °C for 30 min, or exposure to the sulfhydryl blocking reagent, -chloromercuriphenylsulfonate (1 mM) at 25 °C for 30 min, while binding to ABP was unaffected. The isoelectric pH of CR (5.8) was higher than that of ABP (4.6). Dissociation of radioactive 5α-dihydrotestosterone (DHT) from CR and nuclear receptors was extremely slow (half-time at 0 °C >2 days), while dissociation from ABP was rapid (half-time at 0 °C ~ 6 min). Cyproterone acetate (250 mg/100g body weight) inhibited binding to CR both in epididymis and ventral prostate but did not affect binding to ABP. Nuclear uptake was inhibited by cyproterone to the same extent as binding to CR, indicating that nuclear uptake and binding are dependent on CR and independent of ABP. The time-course of uptake and binding in epididymal supernatant and nuclear fractions was essentially the same 1 day after bilateral castration when both CR and ABP were present or 8 days after castration when CR alone was present. It is concluded that the cytoplasmic receptor for androgen in rat epididymis has properties very similar to the androgen receptor in ventral prostate but different from ABP. 相似文献
6.
A. Belanger Lena Lundell P. Eneroth J.A. Gustafsson 《Molecular and cellular endocrinology》1980,19(2):175-181
The metabolism in vitro of 4 androgens, namely testosterone, androstenedione, 5α-dihydrotestosterone and 3α-androstanediol has been studied in male and female rat anterior pituitary cells in primary culture. When testosterone was used as precursor, androstenedione, 5a-dihydrotestosterone and 3α-androstanediol were the main metabolites whereas androstenedione was mainly converted into testosterone, 5α-androstanedione, 5α-dihydrotestosterone and androsterone. Studies on the metabolism of 5α-dihydrotestosterone and 3α-androstanediol showed that these compounds were easily interconverted and were also significantly metabolized to 5α-androstanedione and androsterone. No aromatized compounds could be detected suggesting that androgen action in the pituitary cell occurs directly via the androgen receptor rather than through prior conversion into estrogens. 相似文献
7.
M Engelhardt 《Molecular and cellular endocrinology》1977,8(3):243-257
Treatment of rat thymocytes with cortisol induced an inhibition of [3H]uridine incorporation after 30-90 min, an accumulation of pycnotic cells after 90 min, and a decrease in cell viability after several hours. No cortisol-resistant cells could be distinguished, and dose-response curves for a number of glucocorticoids showed a correlation to the saturation of the glucocorticoid receptors. The pycnotic effect of cortisol increased between pH 5.2--7.0 in parallel with a stimulation of the spontaneous development of pycnotic cells. The cortisol-induced accumulation of pycnotic cells and inhibition of [3H]uridine incorporation varied independently as a function of the cell density, and in a glucose-salt medium only the pycnotic effect of cortisol became inhibited. The inhibition of [3H] uridine incorporation is therefore not an integral part of the pycnotic change of the cells. The glucocorticoid sensitivity was found to increase with the age of the animals, before the onset of thymus involution. 相似文献
8.
GH3/B6 rat prolactin cells were used to analyse at the cellular level the mechanisms by which 17 beta-estradiol (E2) regulates TRH responsiveness of prolactin cells. Before experiments, cells were grown for up to 7 days in 3 different media: normal medium (N) containing 15% horse serum and 2.5% fetal calf serum, CD medium prepared with charcoal-dextran extracted serum and CDE medium supplemented with 4 x 10(-8) M E2. The binding of 3H-TRH (30 min at 37 degrees C) and the TRH-induced percent increase of prolactin release as a function of TRH doses were compared in the 3 conditions. Preculture in E2 enriched medium increased by 50% the number of TRH high-affinity binding sites without modifying their affinity, increased by up to 3 times the percent of the TRH-induced stimulation of prolactin release and improved by one order of magnitude the ED50 of the TRH effect on prolactin release. The presence of HEPES (10 mM) during TRH challenge masked the effect of E2 on the increase in number of binding sites but respected its potentiating effect on prolactin release. 相似文献
9.
James R. Schreiber Kevin Nakamura Gregory F. Erickson 《Molecular and cellular endocrinology》1980,19(2):165-173
It has been hypothesized that progesterone (P) exerts a direct inhibitory effect on ovarian follicular development, an effect which could be mediated by P receptors located in granulosa cells. We tested this hypothesis by examining the effect of several progestins on FSH-stimulated estrogen (E), P, and 20α-dihydroprogesterone (DHP) production by cultured rat granulosa cells, and correlated the results with the ability of the progestins to bind to the granulosa cell P receptor. Granulosa cells from immature hypophysectomized DES-treated rats produced 9 ng/ml E, 21 ng/ml P and 29 ng/ml DHP during a 2-day incubation in McCoy's 5a medium containing 10?7 M androstenedione and 10 ng/ml oFSH. The FSH-induced increase in E production was inhibited by 50 and 95% following concomitant treatment with 3 × 10?6 and 10?5 M resp. of R5020, a potent synthetic progestin. Added R5020 at these concentrations also significantly inhibited P and DHP production. R5020 had no effect on granulosa cell viability or plating efficiency, and the inhibitory action of R5020 on E production was reversible. In studies of the specificity of the progestin inhibitory action, the relative abilities of various progestins to inhibit E production were: R5020 > P > DHP > 17α-hydroxyprogesterone (170HP). The relative abilities of these progestins to bind to the ovary P receptor were also: R5020 > P > DHP > 170HP. These results indicate that exogenous progestins directly inhibit the FSH-stimulation of granulosa cell steroidogenesis in vitro and suggest that the progestin effect may be mediated by the P receptor. Such results offer a possible mechanism whereby progesterone could exert a direct but reversible inhibitory action on ovarian follicular development. 相似文献
10.
Joseph R. Tucci Wolfdietrich Zäh Albert E. Kalderon 《The American journal of medicine》1973,55(5):687-694
Urinary and plasma steroid studies were performed in a 19 year old girl before and after removal of a virilizing arrhenoblastoma. Prior to surgery, base line urinary 17-ketosteroid (17-KS) excretion levels were slightly elevated whereas the plasma testosterone level was markedly elevated and in the normal male range. Individual 17-KS levels were within the normal range, but there was an abnormal androsterone to etiocholanolone ratio. Dexamethasone administration resulted in a fall in plasma testosterone levels and a decrease in urinary 17-KS excretion. The administration of both human chorionic gonadotrophin (HCG) and ACTH was associated with impressive increments in plasma testosterone and/or urinary 17-KS excretion, whereas the administration of HCG alone resulted in increments in only the 11-deoxy 17-KS fractions; ACTH alone raised both the 11-deoxy and 11-oxy 17-KS fractions, with the most notable changes occurring in the former. Within 1 week of surgery, the plasma testosterone level had fallen to normal and urinary 17-KS excretion to subnormal levels. The pre- and postoperative peripheral blood and urinary studies, and the finding of an elevated ovarian vein testosterone level on the side draining the tumor at the time of surgery, demonstrate testosterone secretion by the tumor and, for the first time, an arrhenoblastoma unique in its hormonal responsiveness to dexamethasone, HCG and ACTH. 相似文献
11.
《Scandinavian journal of gastroenterology》2013,48(10):1262-1263
It was recently proposed that the increased biosynthesis of cholestanol in cerebrotendinous xanthomatosis (CTX) is due to increased activity of the Δ5-3β-hydroxysteroid dehydrogenase involved in bile acid biosynthesis, causing increased conversion of cholesterol into cholestanol through 4-cholesten-3-one. Our attempts to confirm this hypothesis have failed. Liver biopsy specimens from two patients with CTX did not have any increased capacity to catalyze conversion of 7α–hydroxycholesterol into 7α-hydroxy-4-cholesten-3-one. Further, we did not find any changes in the activity of liver microsomal Δ5-3β-hydroxysteroid dehydrogenase after feeding rabbits with cholestanol or cholesterol. The findings are discussed in relation to our hypothesis that the accelerated biosynthesis of cholestanol in CTX is due to an increased conversion of early bile acid intermediates into cholestanol. 相似文献
12.
High-affinity binding of the antiestrogen [3H]tamoxifen to the 8S estradiol receptor 总被引:1,自引:0,他引:1
The interaction of tamoxifen (ICI 46,474), a synthetic antiestrogen, with uterine cytosol proteins of immature calf and rat has been studied directly using the tritiated compound labeled with a high specific activity. The binding complexes were measured by the dextrancoated charcoal, protamine sulfate and hydroxyapatite assays. Scatchard plots revealed a single class of high-affinity (KD congruent to 1.7 nM) binding sites, with a binding capacity similar to that of estradiol. Competitive experiments showed the same binding specificity for estrogens and antiestrogens. Sucrose gradient analysis revealed an 8S binding protein which could be partially proteolysed by trypsin into a 4S binding protein. Kinetic studies showed that the association rate of tamoxifen was 5 times lower than that of estradiol and reacted according to a second order kinetics. The first-order kinetics of dissociation was considerably higher than that of estradiol, giving a half-dissociation time of 20--40 min at 0--2 degrees C. In some cases tamoxifen displayed two slopes of dissociation, but the proportion of the slow-dissociating complex was always inferior to that found with estradiol. In contrast to estradiol, the kinetic constants ratio (k-/k+) gave a calculated dissociation constant, similar to that determined in equilibrium conditions (KD), agreeing with a simple reactional scheme. We conclude that the antiestrogen tamoxifen binds directly to the 8S cytosol receptor for estrogens and not to another receptor for the antagonists. In contrast to estradiol, the antagonist is rapidly dissociated from the receptor sites and is unable to protect them against thermal inactivation. The affinity of tamoxifen for its receptor sites as determined directly is surprisingly high when compared to its affinity evaluated indirectly by competitive experiments. It is then suggested that the two ligands either bind on two different sites of the same protein or induce a different conformational change of the same binding site. 相似文献
13.
B M Sanborn J S Elkington R K Tcholakian E Steinberger 《Molecular and cellular endocrinology》1975,3(2):129-142
High-affinity (Ka approximately equal to 5 X 10(8) M-1 for testosterone) androgen-binding activity in rat testis was shown to have a rapid dissociation rate constant (t1/2 = 3 min, 0 degrees C, 30% glycerol buffer) using dextran-coated charcoal to separate bound from free hormone. Because of this fact, exchange of endogenous and labeled hormone was complete in the assay incubation time (16 h, 0 degrees C) and Scatchard plots of the high-affinity binding data were shown to measure total as contrasted to available sites. The binding was highly specific for androgens. Polyacrylamide gel electrophoresis separated high-affinity androgen-binding protein (Rf 0.54) from albumin (Rf 0.62). Binding site estimates under saturating conditions or by Scatchard analysis of electrophoresis data utilizing [3H]dihydrotestosterone agreed reasonably well with estimates made by the charcoal technique using [3H]testosterone. 相似文献
14.
M Mayer E Shafrir N Kaiser R J Milholland F Rosen 《Metabolism: clinical and experimental》1976,25(2):157-167
The mechanism of action of glucocorticoid hormones on rat skeletal muscle was studied by following their effect on muscle weight, free amino acid content, activity of amino acid-metabolizing enzymes, and binding to cytoplasmic receptor proteins. A significant reduction of gastrocnemius muscle and body weight occurred following administration of cortisol, triamcinolone diacetate, and triamcinolone acetonide to adrenalectomized rats. Treatment with triamcinolone diacetate also reduced the level of several free amino acids and enhanced the activity of a myofibrillar protease in skeletal muscle. The hormone had, however, no effect on the activity of various enzymes involved in amino acid catabolism in muscle. In nephrosis, another condition of muscle wasting, the level of several muscle amino acids were also reduced to a lesser extent. Cortisol and triamcinolone acetonide, both of which induce muscle wasting, were found to bind to two distinct cytoplasmic proteins in muscle. Binding of the labeled hormones was followed at 0 C and could be observed in presence of a 1000-fold excess of the catabolically inactive steroid epicortisol. Binding of 3H-triamcinolone acetonide. In vitro competition experiments further suggest a correlation between steroid binding to the 3H-dexamethasone or 3H-triamcinolone acetonide site and their potency to induce muscle catabolism. It is concluded that skeletal muscle is a direct target organ for glucocorticoids, and that muscle responsiveness involves binding of the active hormones to cytoplasmic receptor sites. 相似文献
15.
M.P. Tenniswood P.P. Abrahams C.E. Bird A.F. Clark 《Molecular and cellular endocrinology》1981,22(2):223-229
These studies were designed to further investigate whether 5α-androstane-3β,17β-diol was exerting unique effects on rat prostate acid phosphatase activity or could possibly be exerting its actions by a small peripheral conversion to 5α-dihydrotestosterone. Intraperitoneal administration of 5α-dihydrotestosterone in doses of 1 mg, 100 μg or 50 μg per day starting 7 days after castration led to the restoration of normal characteristics of acid phosphatase activity. However, when 5α-dihydrotestosterone was given in a dose of only 25 μg per day starting 7 days after castration, the changes in acid phosphatase activity were indistinguishable from those found when 5α-androstane-3β,17β-diol was administered in a dose of 2 mg per day. This suggests that the effects of 5α-androstane-3β,17β-diol can be explained by its conversion to small amounts of 5α-dihydrotestosterone. 相似文献
16.
Year-to-year differences in plasma levels of steroid hormones in pre-spawning chum salmon 总被引:1,自引:0,他引:1
Onuma T Higashi Y Ando H Ban M Ueda H Urano A 《General and comparative endocrinology》2003,133(2):199-215
Changes in plasma levels of steroid hormones in pre-spawning chum salmon (Oncorhynchus keta) were examined for 6 years in association with sexual maturation. Fish were sampled along their homing pathway from the coastal sea to the spawning ground from 1995 to 2000. Plasma levels of testosterone (T), 11-ketotestosterone (11KT), estradiol-17beta (E2), 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP), and cortisol were determined by enzyme immunoassays. Sexual maturity was comprehensively estimated by gonadosomatic indices, histology of gonads, nuptial color, spermiation or ovulation ratio. Since the plasma levels of steroid hormones and sexual maturation differed from year to year, they were compared with year-to-year variation of sea surface temperature (SST) of coastal sea to study influence of oceanographic environment on these physiological data. The SST of the migratory route varied among the years, so that we classified the 6 years into cool, intermediate, and warm years. Concerning maturity, the males that returned to the natal hatchery in the warm years were sexually more advanced than those in the cool years. Furthermore, histological data suggested that final oocyte maturation occurred before arrival at the hatchery in one of the warm years, i.e., 1999, while it occurred at the hatchery in one of the intermediate years, i.e., 2000. In the males, T and 11KT levels increased significantly on midway of the homing route in the warm years, whereas they did not show any noticeable changes in the cool years. Furthermore, the levels of T and 11KT on midway of the homing route in the warm years, i.e., 1998 and 1999, were significantly higher than those in one of the cool years, i.e., 1995, in both sexes. In the females, the levels of E2 decreased during upstream migration. Conversely, those of DHP considerably elevated at spawning ground in all years examined. The levels of cortisol were different from year to year regardless of the SST. The present results showed that there were year-to-year differences in plasma levels of steroid hormones and maturity, and some of them may be influenced by the year-to-year variation of SST. 相似文献
17.
Karavashkina TA Kutina AV Shakhmatova EI Natochin YV 《General and comparative endocrinology》2011,170(3):460-467
1-Deamino-arginine vasotocin (1dAVT) induced diuresis and a considerable increase in urinary sodium excretion in female Wistar rats. Sodium fractional excretion rose up to 19.3 ± 1.1%. An increase in urine flow rate after 1dAVT (0.5 nmol/kg body-weight [bw]) injection was accompanied by a significant rise of the solute-free water reabsorption. The 1dAVT-induced natriuresis was as high as natriuresis produced by injection of a maximal dose of furosemide (10 mg/kg bw). V1-receptor antagonists (ОРС-21268, [β-mercapto-β,β-cyclopentamethylenepropionyl1,O-Me-Tyr2,Arg8]-vasopressin) blocked the increase in urinary sodium excretion after the 1dAVT injection. The 1dAVT-induced natriuresis was strongly correlated with an increase in the urinary cGMP and prostaglandin E2 excretion. The natriuretic effect of 1dAVT did not depend on the formation of nitric oxide (NO) or atrial natriuretic peptide of which concentration in the rat blood serum remained stable. The above results indicate that the 1dAVT has unique effects on rat kidney compared to all other known diuretics - it induces extremely high natriuresis and stimulates solute-free water reabsorption. Mechanism of the natriuretic effect of 1dAVT includes decrease in tubular sodium reabsorption due to activation of V1-like receptors and formation of cGMP and PGЕ2. 相似文献
18.
Progestin(norethindrone and norethindrone acetate)-binding protein, exhibiting characteristics similar to uterine progesterone receptor, has been identified in human uterine cytosol. The progestin receptor was characterized by sedimentation coefficient 4.2 S; Stokes radius, 39 Å; frictional ratio 1.29; isoelectric pH 4.6; molecular radius 2.7 nm; and molecualr weight in the range 67 000–74 000. The ammonium-sulfate-precipitated progestin-receptor complex was eluted from a DEAE-cellulose column at 0.18 M KC1. The progestin binding was saturable and stereospecific. The sequential variation in receptor concentration (early proliferative, 3800–4300 sites/cell; late proliferative, 9500–11200 sites/cell; early secretory, 4900–6200 sites/cell; late secretory, 1800–2300 sites/cell) was in conformity for progesterone and the progestins, when concurrently measured. Oral administration of norethindrone significantly reduced the cytoplasmic and nuclear receptor concentration for estradiol and progesterone. A significant observation was that the progestins stabilized the progestin receptor by forming a slowly dissociating complex with a as compared with the progesteronereceptor complex dissociating with . Thus, the uterine progestin receptor recognizes progestins in general, although with a varying degree of affinity, and the altered rate constants could be of putative importance in determining the biological potency of the progestins. 相似文献
19.
S Yotsumoto T Aizawa M Kotani T Yamada 《The Journal of clinical endocrinology and metabolism》1979,48(4):660-663
In a middle-aged woman with virilizing adenoma, 2 mg dexamethasone increased urinary excretion of 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids, whereas 8 mg dexamethasone increased urinary excretion only of 17-KS. With discontinuation of dexamethasone, 17-KS excretion returned to the predexamethasone level. Dexamethasone depressed the basal level of cAMP synthesis and basal testosterone production by the normal adrenal tissue in vitro. Dexamethasone also depressed the increase of cAMP produced by ACTH in the normal tissue. In contrast, dexamethasone increased basal cAMP synthesis and stimulated testosterone secretion in the tumor tissue. ACTH and dexamethasone were additive in their effects on cAMP and testosterone in the tumor tissue. It is suggested that dexamethasone acted directly on the adrenal tumor to stimulate steroid secretion in this patients. 相似文献
20.
Claudio Tiribelli Stefano Bellentani Cesare Campello 《Scandinavian journal of gastroenterology》2013,48(8):805-806
Background: We earlier compared the lactulose/mannitol and 51Cr-ethylenediaminetetraacetic acid (EDTA)/14C-mannitol methods for intestinal permeability We have now investigated an increased number of control subjects, with special regard to the influence of urinary volume, sex, age, and smoking on marker excretion, and patients with intestinal disorders, with special regard to correlations between markers. Methods: The 0- to 6-h urinary excretion of orally administered markers was measured in 65 control subjects and in 70 patients. Results: In the control group excretion of mannitol and 14C-mannitol (small-pore permeability markers) was strongly correlated to urinary volume, whereas such correlation was weak for lactulose and absent for 5lCr-EDTA (large-pore permeability markers). No sex difference in marker excretion was found, but correlation to urinary volume was more pronounced in males. There was a slightly decreasing excretion of markers with increasing age, reaching significance for 5lCr-EDTA and l4C-mannitol; their excretion ratio was unaffected. Smoking did not significantly affect marker excretion. In the patient group the excretion of large-pore markers tended to be higher and that of small-pore markers to be lower than in the control group; correlation between the large-pore markers, between the small-pore markers, and between the large-pore/small-pore marker ratios was higher than in the control group. Conclusions: Correction for urinary volume substantially reduces variability in small-pore marker excretion. Excretion of both types of markers tends to decrease with age, the large-pore/small-pore marker ratio remaining unchanged. Smoking does not affect small-intestinal permeability. 14C-mannitol is preferred to chemically determined mannitol owing to lower test variability. 相似文献