PubMed Health⌕ Search

Biomedical subjects

J H Thijssen

Publications and source records attributed to J H Thijssen.

At least 19 recordsLinked to original sources
PubMed1992

Comparative affinity of steroidal and non-steroidal antioestrogens, cholesterol derivatives and compounds with a dialkylamino side chain for the rat liver antioestrogen binding site.

Steroidal and non-steroidal antioestrogens, steroidal compounds with (disubstituted) dialkyl amino side chain, cholesterol derivatives, histaminic and (anti)-progestational compounds were tested for their ability to compete with [3H]tamoxifen for the specific antioestrogen binding site (AEBS) in the post-mitochondrial fraction of rat liver homogenates. Relative binding affinity was highest for compounds with diethylamino or pyrrolidino ethoxy side chains. Affinity decreased with shortening of this side chain. No connection could be established between the carbon backbone of the compound and affinity, except for the presence of (sometimes aromatic) ring structures. Steroidal ring structures do not seem to be necessary for binding. The cholesterol derivatives, tested in our laboratory, showed very little affinity for the rat liver AEBS. Histamine, melatonin and the (anti)-progestational compounds showed no affinity for the AEBS; and we therefore conclude that the AEBS is not identical to receptors for these compounds. Results of these experiments could be useful in other investigations on the development of resistance of breast cancer to antioestrogens.

Animals↗
PubMed1992

Seasonal changes in performance and free testosterone: cortisol ratio of elite female rowers.

The aim of this study was to investigate the seasonal behaviour of the plasma free testosterone: cortisol ratio (FTCR) and to relate hormonal changes to daily training volume and performance parameters on a rowing ergometer in elite female rowers. During 9 months of training preceding the 1988 Olympic Games the resting values of the FTCR in six elite female rowers were regularly (ten times) studied. Daily training volume was analysed in terms of rowed distance (lrowed) and time (t). In addition, two performance parameters, the power at 4.0 mmol.l-1 lactate concentration in the blood and the maximal power, were determined by a test on a rowing ergometer. The results indicated that the mean FTCR test value did not differ significantly from the level of the initial test or from the mean value of the directly preceding test. A significant negative correlation (r = -0.98, P less than 0.01) between FTCR and lrowed was found in a period i.e. at a training camp, when there was a sudden increase in training volume. When FTCR was related to t a significant positive correlation (r = 0.88, P less than 0.05) was found only for the period at the training camp. Our data further suggested that the FTCR alone was not an adequate indicator for the anabolic/catabolic balance in elite female rowers. This finding was contrary to previous findings in elite male rowers. However, in training practice the FTCR seems useful as an indicator of the hormonal training status of elite female rowers when complemented with data about total and free testosterone, performance parameters and knowledge concerning cyclic variations of the FTCR.

Adult↗
PubMed1992

Stimulation of the pituitary-adrenal axis with a low dose [Arg8]-vasopressin in depressed patients and healthy subjects.

Graded doses arginine-vasopressin (AVP) were administered to depressed patients and control subjects to compare the sensitivity of the pituitary-adrenal system of these subjects for this compound. The plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin were measured before and after intravenous AVP injection. The hormonal output was taken as a measure of pituitary-adrenal function. In control subjects 3 doses AVP and placebo were used, whereas in patients two doses AVP, a low and a high dose, and placebo were tested. All tests were carried out in the afternoon when the pituitary-adrenal system is stable and more susceptible for stimulation. Patients were subdivided into dexamethasone suppressors and nonsuppressors based on their DST status before testing to look for differences among these groups. Control subjects showed no response of the hormones to the lowest dose AVP and a moderate response to the higher doses. Interestingly, depressed patients as compared to controls responded more to the lowest dose AVP in particular with respect to ACTH. DST status did not influence the results. These findings suggest an enhanced sensitivity of the pituitary to low doses AVP in depressed patients. Thus, AVP might play a role in HPA dysfunction in depression.

Adrenocorticotropic Hormone↗
PubMed1992

Effect of wheat bran on excretion of radioactively labeled estradiol-17 beta and estrone-glucuronide injected intravenously in male rats.

Urinary and fecal estrogen excretion were studied in male rats fed a non-fiber wheat starch diet (dietary fiber less than 1%; NF group; n = 4), a low-fiber wheat flour diet (dietary fiber 2%; LF group; n = 4) or a high-fiber wheat bran diet (dietary fiber 11.6%; HF group; n = 3). Short-term effects of the experimental diet on estrogen excretion were studied after i.v. injection of 5 microCi (0.185 MBq) of [14C]estradiol-17 beta (E2) into the tail vein of the rats fed the diets for 2 days. After 3 weeks on the experimental diets, the long-term effects were studied after injection of 5 microCi of [14C]E2 and 10 microCi of [3H]estrone-3-glucuronide (E1-gluc). The diet was found to affect estrogen excretion. The short-term effect indicated that rats fed the HF diet excreted a relatively large amount of labeled compounds in the feces during the first day after injection, while rats fed the NF or the LF diets excreted about half that amount over the same period. On the other hand, urinary excretion of labeled compounds was significantly higher in the NF and LF rats. The long-term effect resulted in steeper slopes (P less than 0.05) of the fecal excretion profiles of rats fed the HF diet as compared with rats fed the NF and LF diets, indicating an accelerated fecal excretion of labeled compounds in the HF rats. The kinetic profiles of 14C and 3H radioactivity in blood plasma indicated a fast decrease (t1/2 of less than 2 min) for both [14C]E2 and [3H]E1-gluc. It was concluded that, owing to the short-term effect of wheat bran intake, during the first 24 h after i.v. administration relatively large amounts of radioactively labeled compounds are excreted in feces of rats fed the HF diet. In contrast, excretion is lower in urine of these rats. When the microflora is adapted to the experimental diet the wheat bran diet still results in an accelerated fecal excretion of labeled compounds, which might be attributed to an interruption of the enterohepatic circulation of estrogens. This might result in lowered plasma and/or tissue estrogen levels and hence a decreased exposure of estrogen-sensitive tissue to estrogens, which might decrease risk on mammary (breast) cancer development.

Animals↗
PubMed1992

Aberrant oestrogen receptor species in human meningioma tissue.

Meningiomas are very rich in progestin receptors (PR) whereas oestrogen receptors (ER) are seldomly found and only at low concentrations. These tumours might possess an ER which is defective in oestrogen binding but still functional in stimulating oestrogen-responsive genes such as PR. In human meningiomas a polymerase chain reaction fragment including the DNA binding domain, the hinge region and the ligand binding domain of ER was amplified. The size of the fragment obtained was as expected from wild type mRNA sequences. Moreover, a variant, which was overexpressed in meningiomas, with a major deletion in exons 2-6 was detected.

Base Sequence↗
PubMed1992

Tissue androgens and the endocrine autonomy of breast cancer.

To evaluate whether a tumour-directed gradient in androgen levels in fatty tissue can account for the maintenance of intra-tissue oestradiol levels, androstenedione (Adione), dehydroepiandrosterone (DHEA), testosterone (Testo) and androstenediol (Adiol) were assayed in breast tumour tissues and in fatty tissue taken at different distances from the tumour. The concentration of Adione was significantly lower in tumour tissue (5.6 +/- 1.5 pmol/g tissue; mean +/- SEM; n = 14) than in the adjacent fatty tissue (20.4 +/- 2.2; P less than 0.005). Testo, by contrast, occurred in equal concentrations in tumour (0.80 +/- 0.11) and in adjacent fatty tissue (0.70 +/- 0.07). Adione levels tended to be lower after the menopause only in fatty tissue, not in the tumour tissue; for Testo no differences were observed between samples from pre- and postmenopausal patients. Tumour DHEA levels (57 +/- 12 pmol/g tissue) were lower than those in fatty tissue (117 +/- 17; P less than 0.02). As with Adione, fatty tissue DHEA concentrations tended to be higher in pre- than in postmenopausal patients. Adiol showed a similar pattern as Testo. For none of the aromatase substrates nor their precursors a tumour-directed gradient was observed. The concentration of Adione in breast cancer tissue is much lower than the reported Km of the aromatase system for Adione. We have concluded, therefore, that the maintenance of oestradiol concentrations in tumour tissues is not substrate-driven.

Adipose Tissue↗
PubMed1992

On the significance of in situ production of oestrogens in human breast cancer tissue.

We have previously shown that human breast cancer is autonomous in the regulation of its intra-tissue oestradiol concentration. Breast fatty tissue does not have this capacity, but rather reflects changes in the peripheral oestradiol concentration. To further evaluate the relative contribution of breast cancer and fatty tissue to the maintenance of tumour oestradiol we investigated whether a tumour-directed gradient in aromatase activity and oestrogen levels existed in mastectomy specimens. No such gradient was found, however, for aromatase, oestrone, oestradiol and their sulphates. Aromatase activity (expressed per gram of tissue) and the concentrations of oestradiol, oestradiol sulphate and oestrone sulphate were higher in tumour than in breast fatty tissue. Fatty tissue had a higher oestrone concentration. It is tentatively concluded that breast tumour aromatase activity is more important for the maintenance of tumour oestradiol levels than aromatase in breast fatty tissue.

Adipose Tissue↗
PubMed1992

Differential effects of arginine on growth hormone releasing hormone and insulin induced growth hormone secretion.

OBJECTIVE: We wished to investigate the interaction of arginine, GHRH and insulin stress on GH secretion. DESIGN: Six healthy, non-obese volunteers underwent seven separate studes in random order. They received (1) insulin alone at 0 minutes; (2) GHRH alone at 15 minutes; (3) arginine alone at 0-30 minutes; (4) arginine at 0-30 minutes and GHRH at 15 minutes; (5) insulin at 0 minutes and arginine at 0-30 minutes; (6) insulin at 0 minutes, GHRH at 15 minutes and arginine at 0-30 minutes; (7) insulin at 0 minutes and GHRH at 15 minutes. MEASUREMENTS: GH and PRL were measured from -30 to 150 minutes at intervals of 15 minutes. RESULTS: Arginine increased GH responses to GHRH and decreased GH responses to hypoglycaemia, but this inhibitory effect of arginine was reversed by GHRH. CONCLUSIONS: The findings suggest that arginine-induced GH release is mainly mediated by a decrease in somatostatinergic tone, while GH responses to insulin stress are probably mediated by both an increase in hypothalamic GHRH release and inhibition of somatostatin.

Adult↗
PubMed1992

High affinity growth hormone binding protein in plasma of patients with acromegaly and the effect of octreotide treatment.

OBJECTIVE: The objective of this study was to investigate the effect of plasma GH-levels on the high affinity growth hormone binding protein (GHBP). PATIENTS: We studied plasma samples of eight patients with acromegaly and eight age and sex matched healthy subjects. DESIGN: Patients with acromegaly were treated with octreotide administered by continuous subcutaneous infusion. Levels of growth hormone binding protein (GHBP) were measured in plasma samples before therapy and 3, 6 and 12 months after starting treatment. During this period, octreotide was administered in doses of 300-800 micrograms/day. The mean dose per patient over the study period ranged from 300 to 575 micrograms/24 h. The GHBP levels of patients with acromegaly were compared with those in the healthy subjects. MEASUREMENTS: Bound and free 125I-GH in plasma were measured using FPLC gel chromatography on a Superose 12 column, after an overnight incubation period. The binding data were used for a Scatchard plot analysis. Wilcoxon's signed rank test was used for statistical analysis. RESULTS: We found lower GHBP levels in acromegalic patients (P = 0.01) than in the control subjects. Octreotide treatment resulted in IGF-I levels < 300 micrograms/l in four patients. In these patients GHBP levels increased. CONCLUSIONS: We conclude that growth hormone binding protein levels are down regulated in acromegaly, indicating an important role for GH in the regulation of this protein.

Acromegaly↗
PubMed1992

Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls.

The rate at which girls progress through the stages of puberty in relation to body fat mass and body fat distribution and its relation to their hormonal profiles was studied. Sixty-eight schoolgirls participated in a longitudinal study during 3 yr. The girls were divided into subgroups with increasing skinfold thicknesses and waist-hip ratio. They were also grouped depending on Tanner's breast development classification (M2 and M3). The age at M2 was only marginally correlated with the menarcheal age, but the age at M2 and the time interval from that age to menarche was negatively correlated. Age at the onset of puberty was not related to body fat mass or distribution. The rate of pubertal development after pubertal stage M3 was negatively related to the body fat mass. Age at M2 was only correlated with estrone (E1), while the rate of pubertal development was associated with higher FSH, E1, estradiol (E2), the fraction of E2 that was not bound to sex-hormone-binding globulin (non-sex-hormone-binding globulin bound E2) and androstenedione plasma levels at the onset of puberty. Body fat distribution, rather than body fat mass was related to the total and the non-sex-hormone-binding globulin bound plasma levels of E2 and testosterone at the onset of puberty. Changes in body fat distribution in early female puberty were chiefly related to the waist circumferences. We found no evidence that body fat mass or body fat distribution triggers the onset of puberty. Body fat distribution was related to early pubertal endocrine activity. Body fat mass was negatively related to the rate of pubertal development toward menarche, but no clear indications for an endocrine-related process is found. We conclude that onset of puberty and menarche are not parallel pubertal events, and that early pubertal plasma E1, E2 and androstenedione levels are predictors for the rate of pubertal development toward menarche. We propose that the control of the onset of puberty and maturation of the hypothalamic-pituitary gonadal axis, with regard to negative feedback control, are at least partially independent. This induces on the average a "catch up" pubertal maturation in girls with a late onset of puberty.

Adipose Tissue↗
PubMed1992

Effects of wheat bran and energy restriction on onset of puberty, cell proliferation and development of mammary tissue in female rats.

Delayed onset of puberty and mammary development is assumed to reduce the risk of mammary cancer. An animal experiment was performed to investigate the influence of dietary fiber, which is known to affect hormonal balance, on these characteristics. Forty-five immature female rats were randomized into three groups, which were fed ad libitum a low-fiber diet (less than 0.5% dietary fiber based on white wheat flour), a high-fiber diet (9.2% dietary fiber based on wheat bran), or an energy-restricted low-fiber diet providing 90% of the energy of the ad libitum low-fiber diet. Energy intake in the second and third groups was similar. Wheat bran slightly delayed onset of puberty, whereas restricted energy intake delayed onset of puberty by about six days. At 48-58 days of age, 14 rats of the low-fiber group, 10 of the high-fiber group and 7 of the restricted group were in cycle. Development of mammary tissue was rudimentary in rats of the energy-restricted low-fiber group, stronger in the high-fiber group and strongest in the ad libitum low-fiber group. Cell proliferation in mammary tissue was similar for both groups fed ad libitum, but significantly lower in the restricted group. Peroxidase activity, a biomarker for estrogenicity, was lower in the high-fiber group than in the two low-fiber groups. It is concluded that wheat bran and, even more effectively, an imposed restricted energy intake delays onset of puberty and mammary development. This shortens the time for mammary cells to be initiated to tumor cells and hence reduces the risk of mammary cancer development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of wheat bran on blood and tissue hormone levels in adult female rats.

The protective effect of dietary fiber on breast cancer development might be explained by the interaction between dietary fiber and hormonal processes. We studied the effects of dietary fiber and the effects of a reduced energy intake on the exposure of mammary tissue to both estrogens and progesterone, as well as the blood plasma levels of these steroids and of LH and FSH. Adult female Fisher rats were fed ad libitum either a low-fiber diet (0.5% dietary fiber based on wheat flour) or a high-fiber diet (9.2% dietary fiber based on wheat bran). A third group was used to control for the reduced energy intake of the high-fiber group and was fed the low-fiber diet restricted. Energy intake was similar for the second and third groups. Four out of 14 rats of the high-fiber group and 4 out of 15 rats of the restricted low-fiber groups were not in cycle after seven weeks on the experimental diets, indicating that the estrous cycle was significantly affected by a reduced energy intake. Exposure of mammary tissue to estrogens did not differ among the groups, as measured by estrone, estradiol-17 beta, estriol and peroxidase activity. During the peak period, plasma LH levels were significantly higher in the high-fiber group than in the two low-fiber groups. FSH and progesterone plasma levels were unaffected by the experimental diets. It is concluded that dietary fiber affects the hormonal processes involved in breast cancer development. The increased LH levels indicate an increased estrogen production in the ad libitum high-fiber group.

Animals↗
PubMed1992

Estrogens in plasma and fatty tissue from breast cancer patients and women undergoing surgery for non-oncological reasons.

Breast cancer tissue is able to maintain the tissue estradiol level in spite of the massive decrease in plasma estradiol associated with menopause, whereas fatty tissue from breasts with malignancies more closely reflects the changes in plasma. In the present study estrone and estradiol levels in fatty tissues from different origins were compared to evaluate the capacity of distant fatty tissues to act as estrogen reservoirs. Abdominal fat was obtained from 25 premenopausal and 20 postmenopausal women who underwent surgery for non-oncological reasons. Estrone and estradiol levels in these tissues were compared to those in breast fatty tissue from breast cancer patients. Plasma estrogen levels were not different in the two groups. In both groups, median plasma estradiol levels dropped sharply with menopause (from 363 to 40 pmol/l in breast cancer patients; from 280 to 45 pmol/l in the non-oncological patients; p less than 0.002), whereas a significant decrease in plasma estrone was observed only in the breast cancer patients (from 238 to 140 pmol/l; p less than 0.02). In premenopausal women, median estrone and estradiol levels in breast fatty tissue (1135 and 375 fmol/g, respectively) and abdominal tissue (1390 and 470 fmol/g, respectively) were not different. In postmenopausal women, however, significantly higher estrone levels (663 vs. 508 fmol/g; p less than 0.01) and estradiol levels (245 vs. 187 fmol/g; p less than 0.02) were found in abdominal fatty tissue. In view of the absolute estrogen levels in breast and abdominal fatty tissue and in plasma, we conclude, however, that it is unlikely that remote fat contributes substantially to the maintenance of estrogen levels in breast cancer tissue.

Abdomen↗
PubMed1991

Absence of detectable immunoreactive alpha melanocyte stimulating hormone in plasma in various types of Cushing's disease.

We have measured alpha-MSH in plasma of normal subjects and subjects with various diseases of the pituitary-adrenocortical system using a radioimmunoassay with a sensitivity of 1.2 pmol/l. No alpha-MSH could be detected in plasma of normal subjects (n = 6), in plasma of patients with Addison's disease (n = 3), Nelson's syndrome (n = 2), bromocriptine responsive (n = 2) and unresponsive (n = 5) Cushing's disease and in plasma of psychiatric patients on chronic treatment with the dopamine antagonist haloperidol (n = 5). Plasma alpha-MSH remained undetectable in 2 patients with Cushing's disease after iv injection of 60 micrograms/kg haloperidol. In contrast, alpha-MSH was detectable in plasma of normal dogs (n = 2) and dogs with pituitary dependent hyperadrenocorticism (n = 2), whereas the iv injection of halo peridol was associated with a rise of plasma alpha-MSH. Thus we are unable to detect circulating alpha-MSH in man despite the use of a sensitive radioimmunoassay.

Addison Disease↗
PubMed1991

Endogenous steroid hormones and local aromatase activity in the breast.

To test the hypothesis of an increased activity of the enzyme aromatase in adipose tissue from affected when compared with non-affected quadrants of patients with breast cancer, the aromatase activity has been measured in tumour and fatty tissues dissected at specific sites from the breasts of 16 patients. Activity was measured after extensive purification of the product formed. Results, expressed in fmol/g of tissue, did not show a higher activity in the affected vs the non-affected quadrants. In the tumours, higher activities were found when expressed per g of tissue. Per mg of DNA, an indicator of the number of cells, tumour enzymatic activity was lower than in fatty tissues. The relations between the products of aromatase, oestrone and oestradiol in the various tissues point to the importance of additional enzymatic processes, especially of the reductive 17 beta-oestradiol dehydrogenase, in the accumulation of high quantities of oestradiol in the malignant tissue.

Adipose Tissue↗
PubMed1991

Influence of wheat bran on NMU-induced mammary tumor development, plasma estrogen levels and estrogen excretion in female rats.

In our animal experiments the hypothesis was tested that a high-fiber (HF) diet reduces tumor promotion by interruption of the enterohepatic circulation resulting in lowered estrogen exposure of the estrogen-sensitive tissue. In the first experiment the development of N-nitrosomethylurea (NMU) induced mammary tumors was investigated. One group of rats (HF) was fed a HF diet (11% fiber, based on wheat bran), the other group (LF) fed a low-fiber diet (0.5% fiber, based on white wheat flour). Tumor incidence (90 and 80%, respectively) and latency (121 and 128 days, respectively) were similar in the HF and LF groups. Compared to the LF group, HF rats had lower tumor weights (0.16 vs 0.55 g; P less than 0.01) and a slightly lower tumor multiplicity (1.8 vs 2.8 tumors per tumor-bearing rat). These differences were reduced after adjustment for body weight. In a second experiment rats, not treated with the carcinogen, were kept on the same HF and LF diets. From these rats 24-h urine and feces and orbital blood samples were collected for analysis of (un)conjugated estrogens. The excretion of both free and conjugated estrogens in fecal samples was about 3-fold higher in HF rats than in LF rats. During the basal period of the cycle urinary excretion of estrone was lower in HF rats (mean 9.7 ng/day) than in LF rats (mean 13.0 ng/day; P less than 0.05). It is concluded that wheat bran interrupts the enterohepatic circulation of estrogens, but plasma levels are not affected. Whether the development of mammary tumors is reduced by the introduction of specific components of wheat bran, or by a reduced body weight due to a lower (effective) energy intake remains to be determined.

Animals↗
PubMed1991

In vitro binding of estrogens by dietary fiber and the in vivo apparent digestibility tested in pigs.

Within the framework of experiments related to the association between dietary fiber and breast cancer an in vitro test system was used to study the binding of estrogens to various fibers (e.g. cholestyramin, lignin and cellulose) and fiber sources (e.g. wheat bran, cereals, seeds and legumes). Furthermore, the in vivo apparent digestibility of the different fiber sources was tested using a mobile nylon bag technique in intestine-cannulated pigs. Estradiol-17 beta (E2) bound more strongly to the various fibers than did estrone (E1), estriol or estrone-3-glucuronide. At increasing pH (greater than 7) binding of both E1 and E2 to wheat bran decreased significantly. Cholestyramine and lignin bound almost all estrogens present in the medium. Linseed (91%), oats (83%), barley chaff (88%) and wheat bran (82%) are other excellent binders of E2. Corn, rye and white wheat flour showed lower binding capacity with a relatively low affinity. Cereals with the highest percentage of lignin in the fiber (greater than 3%) were also the fiber sources with the lowest apparent digestibility. Estrogens bound with the highest affinity (relative to bovine serum albumin) to these fiber sources. Together with wheat bran and lignin, oats, linseed and soybean seem to be products with good perspectives for in vivo evaluation of the lowering effect of dietary fiber on estrogen exposure of estrogen-sensitive tissues.

Animals↗