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Biomedical subjects

J Poortman

Publications and source records attributed to J Poortman.

At least 37 records · Page 2Linked to original sources

Effects of oestriol: preliminary results on receptor kinetics in target tissues of postmenopausal women.

This in vivo investigation was done to study the effects of intravaginal oestriol (E3) administration on endometrial, myometrial and vaginal tissue of normal postmenopausal women. All women received intravaginal E3- suppositoria (containing 0.5 mg E3) once a day for 3 weeks prior to hysterectomy. The medication was continued until the day of operation. At the time of operation both uterine and vaginal tissue was obtained. The receptor content in the cytosol was measured by a multiple point-dextran -coated-charcoal assay using [3H]E2 and [3H]ORG-2058 as ligands. The receptor content in the nucleus was measured by incubating purified whole nuclei in 10 nM [3H]E2 for 18 h at 0 degrees C. We have shown that under these conditions there is a total exchange of all occupied receptors. Preliminary data on 4 patients are available. Vaginal cytology clearly showed an increase of the maturation value. Oestrogen receptor concentrations in the cytosol of all three tissues studied were lower than those obtained in untreated women, suggesting nuclear transformation of the receptor as a consequence of treatment. The nuclear E2 receptor levels cannot be compared with normal women yet. Progesterone receptors in endometrial and myometrial cytosol seemed to be higher than those in untreated women, indicating effects of the treatment. In the human, vaginal progesterone receptor cannot be used as a marker for oestrogenic stimulation because only exceptionally could their presence be detected in either treated or untreated women.

Aged↗

Measurement of endogenous subcellular concentration of steroids in tissue.

A reliable method for the extraction of steroid hormones from human uterine tissue and the subsequent measurement of these hormones in the subcellular compartments by radioimmunoassay is described. Extraction of radioactive steroid hormones from in vivo labelled human uterine tissue by different methods reveals that an almost quantitative extraction of steroid hormones from the nuclear fraction is obtained by sonication in ethanol-acetone. Extraction of steroid hormones with diethylether from a high speed cytosol is incomplete. Using a more potent denaturating agent prior to extraction with diethyl ether leads to complete extraction of unconjugated steroids.

Androgens↗

The endogenous concentration of estradiol and estrone in normal human postmenopausal endometrium.

The endogenous estrone (E1) and estradiol (E2) levels (pg/g tissue) were measured in 54 postmenopausal, atrophic endometria and compared with the E1 and E2 levels in plasma (pg/ml). The results from the tissue levels of both steroids showed large variations and there was no significant correlation with their plasma levels. The mean E2 concentration in tissue was 420 pg/g, 50 times higher than in plasma and the E1 concentration of 270 pg/g was 9 times higher. The E2/E1 ratio in tissue of 1.6, was higher than the corresponding E2/E1 ratio in plasma, being 0.3. We conclude that normal postmenopausal atrophic endometria contain relatively high concentrations of estradiol and somewhat lower estrone levels. These tissue levels do not lead to histological effects.

Aged↗

Plasma-exchange in the treatment of severe thyrotoxicosis in pregnancy.

Three female patients with severe thyrotoxicosis, two of them pregnant 22 and 16 wk, respectively, were treated with plasma-exchange (PE) combined with anti-thyroid drugs. In both pregnant patients PE was an effective adjunct to therapy with low-dose carbimazol. They were both delivered of normal babies at 37 and 40 wk, respectively. One newborn was euthyroid, the other had transient neonatal thyrotoxicosis. In the non-pregnant patient an ominous situation of thyrotoxic crisis was rapidly reversed by a single PE. During PE an influx of thyroid hormones occurs from the extra- to the intravascular compartment, which increases the efficacy of PE. The 5% albumin solution derived from human donor plasma, used as replacement fluid, contained substantial amounts of thyroid hormones. A 5% albumin solution from human placental origin lacks these hormones and is therefore recommended as replacement fluid for PE in thyrotoxicosis. There are no valid arguments for advocating replacement with donor plasma.

Adult↗

Subcellular distribution of androgens and oestrogens in target tissue.

To study the endogenous concentration of androgens and oestrogens in target tissue, three different methods have been used: (a) measurement of concentration gradient across mammary tumours, (b) long-term infusion of subphysiological amounts of labelled oestrogens and measurement of tissue-plasma gradients in human uterine tissue and (c) measurement of endogenous concentrations in mammary and uterine tissues. In addition to the tissue-plasma gradient, the subcellular distribution was also measured. An improved method is presented for processing the tissue and for the quantitative extraction of steroid hormones from cytosol and nuclear fraction. The data obtained show clearly that steroid hormones have a tissue-plasma gradient that varies from tissue to tissue and from one hormone to another. As steroid hormones exert their influence intracellularly at the site of receptor binding, our findings may have major consequences for the study of hormone-related cancers of the breast and of the uterus.

Androgens↗

[Oestrogens in the cell: differences between uterine and mammary tissue].

The studies reported here on the distribution of oestrogens in different cellular compartments in the uterine and mammary tissue, which was determined by means of a new extraction method, show great differences in concentration of oestradiol and oestrone in the cellular nucleus and in the cytosol. These data are very difficult to reconcile with the conventional model of the mechanism of action of the oestrogens in the cell. The results would rather indicate that the chemically detectable receptors are not freely available without exception to all steroids in the cytosol of the cell.

Breast↗

Steroid and pituitary hormone concentrations in the fluid of preovulatory bovine follicles relative to the peak of LH in the peripheral blood.

Preovulatory bovine follices (n = 73) were collected at different times after the onset of oestrus until shortly before ovulation, which occurred at 24 +/- 1 X 4 h after the peak concentration of LH in the peripheral blood. Non-atretic antral follicles (n = 9) of 15-19 mm were also collected from cows during the luteal phase of the oestrous cycle. Follicular fluid concentrations of dehydroepiandrosterone, androstenedione and oestrone, and of LH, FSH and prolactin were compared in 2-h periods relative to the LH plasma peak. Before the LH surge the concentrations of the steroids were much higher than in non-atretic luteal-phase follicles of similar size. From 0 to 6 h after the LH peak the steroid concentrations decreased sharply to remain low until ovulation; only that of androstenedione increased again after 14 h to remain constant. The ratio between the concentrations of androstenedione and dehydroepiandrosterone remained constant until 14 h after the LH peak; at 14 h it increased about 4-fold and remained high until ovulation. The ratio between the oestrone and androstenedione concentration increased gradually to a 10-fold higher value until at 14 h an abrupt decrease was observed. These changes indicate that after the LH peak androgen production is directly inhibited and, at a slower rate, the aromatizing activity. Androstenedione appeared to be the major aromatase substrate. Before the plasma LH peak the follicular fluid concentration of FSH was higher than in luteal-phase follicles; the concentrations of LH and prolactin were not different from those in luteal-phase follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Ketosteroids↗

Progesterone receptors in human oestrogen target tissues.

The levels of specific oestrogen and progesterone receptors have been measured in myometrial, endometrial and vaginal tissues obtained from 18 women between the ages of 28-73 yr. High speed cytosols of the three tissues were incubated at four different concentrations of specific ligands: E2 for the oestrogen receptor (ERc) and Org-2058 for the progesterone receptor (PgRc). Separation of bound and free hormones was done by dextran-coated charcoal; data were analysed according to Scatchard. In the myometrium and endometrium both PgRc and ERc were found. In the vaginal tissues obtained from the same patients only ERc was present. There was no evidence of specific progesterone receptors in the vagina. Both clinical and histological findings indicate that the vagina is an oestrogen-sensitive organ. Therefore, it is surprising that progesterone receptors, which are considered to be a specific response of oestrogen target tissue, are absent in the human vagina. This finding suggests that the induction of the progesterone receptors is not a specific response to oestrogen stimulation in the human vagina.

Adult↗

Weight reduction and oestrogen excretion in obese post-menopausal women.

The urinary excretion of oestrone (E1), oestradiol (E2) and oestriol (E2) was measured in 42 obese post-menopausal women before and 6-12 mth after their participation in a weight reduction programme. The method of inducing weight loss was based on modification of eating behaviour without specific changes in dietary composition. Urinary oestrogen, as a ratio to creatinine, were measured by a specific radioimmunoassay after purification of the specific oestrogen fraction. Before weight reduction efforts, there is a significant correlation among E1, weight and the Quetelet-index and between E3 and the Quetelet-index. These correlations have disappeared after weight reduction. There is a significant positive correlation between changes in body-weight and changes in the excretion of E1, E3 and total oestrogens. There was no significant change in the so-called oestrogen ratio (E1 + E2/E3) in relation to change in body weight. With respect to the statistical association between endometrial cancer, breast cancer and overweight, our data give support to the concept that intervention programmes on weight reduction may influence both the incidence and the prognosis of these two diseases.

Body Weight↗

Absence of seasonal variation of estrogen receptor levels in human breast cancer tissue.

The concentration of estrogen receptors was measured in 979 human primary breast cancer tumors obtained during 4 consecutive years. Of these tumors, 631 were classified receptor positive and originated from 212 premenopausal and 419 postmenopausal patients. A modified EORTC procedure was used to quantify the receptor content. Several statistical analyses were performed on the data from the premenopausal and postmenopausal patients separately and on the combined data. The results of these analyses do not support the existence of any periodicity in the estrogen receptor level which is significant and consistent from year to year.

Breast Neoplasms↗

Plasma oestrone, oestradiol and androstenedione levels in post-menopausal women: relation to body weight and height.

To study the relation between body weight and height and the plasma sex-hormone levels wer measured the plasma levels of oestrone (E1), oestradiol (E2) and androstenedione (A) in a group of healthy post-menopausal women with a wide range of body weight. The sex hormones were measured by radioimmunoassay with highly specific antisera after purification of the plasma extract by column chromatography. Our findings show that there is significant positive correlation between the E1 level and body weight as well as A level and, to a lesser extent, between the E1 level and Quetelet index. For E2 there is no correlation with these parameters. There is also a very slight correlation between A level, body weight and Quetelet index. Calculation of the partial correlation coefficient shows that E1 correlates to the same degree with body weight and A level, whereas the A level does not correlate with body weight at a fixed value for the E1 level. We conclude that variation in the E1 level depends to the same degree on the variation in body weight as well as the variation in A level.

Androstenedione↗

Relationship of weight to the promotion of breast cancer after menopause.

Epidemiologic and experimental evidence for a relation between high body weight and breast cancer is reviewed. A prospective study in the framework of a population-based breast cancer screening project for women over age 50 with determination of estrogen-receptor-status of cancers has provided evidence that promotion of ER-positive cases is favored by obesity and relatively inhibited by leanness. In lean postmenopausal women, clonal selection is thought to lead to a preponderance of ER-negative cells in the cancers. Initiation of breast cancer is probably unrelated to obesity. Induction of breast cancer may be rare after menopause, but existing tumors grow if they receive stimuli to which they are sensitive. A lead to further research is presented.

Aged↗