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Biomedical subjects

J Poortman

Publications and source records attributed to J Poortman.

At least 55 records · Page 3Linked to original sources
PubMed1981

Actions and interactions of delta 5-androstene-3 beta, 17 beta-diol and 17 beta-estradiol in the immature rat uterus.

delta 5-Androstene-3 beta, 17 beta-diol (Adiol), in a dosage of 1000 microgram/24 h injected ip into immature female Wistar rats (21-23 days old), induced 72 h after the injection the same elevations of uterine weight, cytosol protein, nuclear DNA, cytosol estrogen and progesterone receptors, and nuclear estrogen receptor levels as did 17 beta-estradiol (E2) in a dosage of 2.5 microgram/24 h. Adiol appeared to translocate the estrogen receptor and induce the synthesis of estrogen and progesterone cytosol receptors in a manner almost identical to that of E2. Studies on the metabolism of tritiated Adiol ruled out the possibility that the estrogenic effects of Adiol might be mediated by conversion to E2. Small doses of Adiol (100 microgram), which alone did not result in estrogenic effects, enhanced the effect of 2.5 microgram E2 on uterine weight and progesterone receptor levels, whereas a dosage of 100 microgram dihydrotestosterone neither enhanced nor inhibited the uterine growth induced by 2.5 microgram E2. A role for the androgen receptor in the synergism between Adiol and E2, therefore, appears to be ruled out. When Adiol in a dosage of 1000 microgram was administered together with 2.5 microgram E2, there was no important difference compared to either steroid alone up to 6 h. Thereafter, a very pronounced and prolonged secondary wave of translocation of the E2 receptor to the nucleus occurred which can explain the synergism between E2 and Adiol that became apparent in the same time interval. This secondary wave of translocation is most likely related to the persistent presence of both Adiol and E2 at the time of replenishment of the cytosol receptor (3-6 h after the injection). It is concluded that delta 5-androstene-3 beta, 17 beta-diol acts in the immature rat uterus like a fully potent estrogen with a complete lack of antiestrogenic effects. In this respect it differs from androgens like testosterone and dihydrotestosterone which can display both estrogenic and antiestrogenic activities.

Androstenediol↗
PubMed1980

Estrogen receptors in human vaginal tissue.

The presence of specific estrogen receptors could be demonstrated in vaginal tissue, obtained during operation from 38 women, age 27--75 yr. In 23 premenopausal women the receptor concentration in the vaginal tissue varied between 12 and 91 fmol/mg protein, no significant difference in the receptor level was found between the proliferative and secretory phase of the menstrual cycle, classified by endometrial histology. In 15 postmenopausal patients, the receptor level varied between 4 and 119 fmol/mg protein. In the last group a significant negative correlation (R = -0.72) was found between the vaginal estrogen receptor level and the Maturation Value of the vaginal smear; no correlations were found between the receptor level and the plasma levels of estrone, estradiol, LH, FSH and SHBG. No systematic differences in the receptor concentration in various parts of the vagina were observed. There was no correlastion between the receptor level and age of the patients.

Adult↗
PubMed1980

Influence of physical exercise on sex-hormone metabolism.

We have studied the effects of short-term exercise on the degradation rate of estradiol (E2) measured as the metabolic clearance rate (MCRE2). Six young women (mean age 20.7 yr) volunteered for this study in which we investigated the influence of a submaximal bicycle ergometer load on the MCRE2. All measurements were done in the morning of the 7th to 10th day of the menstrual cycle. [3H]estradiol 17 beta ([3H]E2) was administered intravenously at a constant rate by an infusion pump. During the exercise period on the bicycle ergometer (70% VO2max, 10 min) and the recovery period (25% VO2max, 30 min), several blood samples were taken in which the [3H]E2 concentration was estimated. The results showed a strong decrease in the MCRE2 (range 18-67%) at the end of the work load for all the volunteers. At the end of the recovery period, the MCR was still lower than the basal value (range 30-50%). The possible mechanisms and relevance of these exercise-induced MCR changes of estradiol are discussed.

Adult↗
PubMed1980

Plasma prolactin levels in women at postmenopausal age with a family history of breast cancer or a prescription for antihypertensive Rauwolfia treatment.

An investigation was made of daytime plasma prolactin levels in three groups of women aged 50 to 64 years: (1) 139 women with a family history of breast cancer; (2) 50 women on Rauwolfia treatment for hypertension, and (3) 90 women of a control group. A significant difference in prolactin levels was found between groups 2 and 3 but not between 1 and 3. These findings are considered in relation to the results of a breast cancer screening programme in which the women took part. Here, it was the women with a family history of breast cancer who showed an increased breast cancer risk, whereas the risk in women on Rauwolfia was not significantly higher than expected on the basis of the experience among controls. It is concluded that the role of prolactin in the etiology of breast cancer is still not clear.

Breast Neoplasms↗
PubMed1979

Ratio of 11-desoxy 17-oxosteroids to creatinine in a population screened for breast cancer.

During a population-based screening project for breast cancer, almost 15,000 women aged 50 years and over have provided a 12 h (overnight) sample of urine for research purposes. In 3,789 women the excretion of 11-desoxy-17-oxosteroids (DOOS) and creatinine was measured. Results were analysed in terms of urinary concentrations and of a ratio between DOOS and creatinine. Age had an effect on DOOS, creatinine and their ratio. Body weight and body surface area had an effect on creatinine excretion and therefore on the ratio. The following variables did not have an appreciable effect on the above-mentioned ratio: a family history of breast cancer, parity and age at first pregnancy, menopause and oestrogenic drugs, and parenchymal pattern of the breast as observed on the xeromammogram. Breast cancer was found at first screening in 106 out of 14,697 women. In 100 of these cases DOOS and creatinine were measured. Excretion values expressed as the ratio between the two, allowing for body surface area, did not differ materially from those of 100 age-matched controls. These results lead the authors to the conclusion that the determination of androgen metabolite excretion in women over 50 years of age is of no help in selecting a group at high risk of breast cancer.

17-Ketosteroids↗
PubMed1978

Oestrogen binding proteins in bone cell cytosol.

Attempts were made to demonstrate the presence of specific oestrogen binding proteins ("receptors") in bone cells. High speed cytosol preparations of bone were incubated with several concentrations of radioactive oestradiol alone and with radioactive oestradiol in the presence of a specific antioestrogen, Nafoxidine. Separation of bound and free oestradiol was carried out by dextran coated charcoal treatment and by sucrose gradient ultracentrifugation. Several types of bones likely to be oestrogen-sensitive were investigated: human femoral heads, human phalanx, rat and rabbit calvaria, humeri and femora of female rats. In all experiments we were unable to demonstrate the presence of specific oestrogen receptors in bone cell cytosol indicating that the direct effect of oestrogens on bone, if present, is not mediated by specific oestrogen receptors.

Animals↗
PubMed1977

Relative binding affinity of androstane and C-19-nor-androstane-steroids for the estradiol-receptor in human myometrial and mammary cancer tissue.

The relative binding affinity of several androstane- and C-19-nor-androstane-compounds for the estradiol (E2)-receptor in human myometrial and mammary cancer tissue was studied. High speed cytosol was incubated with tritiated E2 alone as well as in the presence of increasing amounts of the compound to be tested. The highest affinity is found for steroids with two hydroxyl-groups at C-3 and C-17 in the beta-position and a double bond at C-4-5 or C-5-6. Saturation of the A-ring decreases the affinity: 5alpha-compounds have less affinity, 5-beta-compounds have less affinity; 5beta-compounds hardly any affinity. The presence of a hydroxyl-group in the 3alpha, 11beta or 16beta-position decreases the affinity, as dose a 3-oxo or 17-oxo-group. Removal of the C-19-methyl-group facilitates the binding. This data led to the concept that flatness of the A-ring in respect to the B-ring of the steroid molecule is a principal requirement for binding to the E2-receptor. The rank order of RBA is identical in myometrium and in mammary cancer tissue, indicating that estrogen-receptors are at least highly similar in both target tissues.

Androstane-3,17-diol↗
PubMed1976

A semiautomated method for the determination of 11-deoxy-17-oxo-steroids in urine.

A semiautomated method is described for the determination of total 11-deoxy-17-oxo-steroids (11-DOOS: androsterone, etiocholanolone plus dehydroepiandrosterone) in urine. Urinary conjugates are manually extracted on a XAD-2 resin, hydrolysed by beta-glucuronidase and "solvolysed" in acid ethyl-acetate according to Burnstein-Lieberman. The free 11-DOOS are extracted automatically with iso-octane and estimated colorimetrically by the Zimmerman reaction in an Auto-Analyzer II system. The method was evaluated by investigation of its precision, accuracy, sensitivity and specificity. It was found to be satisfactory for the rapid and reliable screening of large numbers of urine samples.

Androsterone↗
PubMed1975

Interaction of delta-5-androstene-3beta, 17beta-diol with estradiol and dihydrotestosterone receptors in human myometrial and mammary cancer tissue.

Specific receptor binding of estradiol (E-2) and dihydrotestosterone (DHT) was studied in human myometrial tissue and in human mammary cancer tissue. The inhibition of binding for E-2 and DHT by E-2, testosterone (T), DHT, dehydroepiandosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), androstendione (A) and 5-androstene-3beta, 17beta-diol (Adiol) was tested with the use of dextran-coated charcoal separation of bound and free E-2, respectively, and DHT. The percentage of binding inhibition was calculated with reference to the inhibition obtained with nafoxidine in a molar concentration ratio of 1,000 for E-2 binding, respectively, with cyproterone acetate in a molar concentration ratio of 10,000 for DHT binding. In 15 samples of myometrium tested, receptors were found for both E-2 and DHT. From 19 samples of mammary carcinoma tissue one showed no binding activity, three samples did bind E-2 only, five samples DHT only, and ten samples showed binding of both steroids. A 50% inhibition of E-2 binding, in myometrial as well as in tumor tissue, required a molar concentration ratio of 40 for Adiol, of more than 2,000 for DHEA. No significant inhibiting activity could be found for A up to a molar concentration ratio of 10,000 and for DHEA-S up to 40,000. With regard to DHT binding, Adiol is more active than E-2 and less active than T. Of the substances tested Adiol is therefore the only one which exerts a significant inhibiting influence at a molar ratio not far beyond the physiological range. This signifies that Adiol might interfere at the receptor level in the estrogenic stimulation of mammary cancer cells.

Adult↗