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Biomedical subjects

J Spona

Publications and source records attributed to J Spona.

At least 199 records · Page 11Linked to original sources

Hormone serum levels during oral cimetidine treatment of patients with peptic ulcers.

Radioimmunoassayable basal serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (hPRL), 17 beta-estradiol (E2) and testosterone (T) were estimated in a total of 68 patients, who were treated because of peptic ulcer with 1 g cimetidine per day. 37 patients were male and 31 were female subjects, respectively. Hormone serum levels were assayed before and 4 to 6 weeks after start of therapy. A significant increase of LH serum levels (p less than 0.025) and a significant decrease of hPRL (p less than 0.025) was noted in the male subjects during therapy. Similarly, a decrease of hPRL serum levels (p less than 0.001) was registered in the female subjects during treatment with 1 g cimetidine per day. All other hormone serum levels in both female and male subjects remained unchanged. The present data combine to suggest that 1 g cimetidine per day does not provoke hyperprolactinemia. In addition, cimetidine at the dose used does not interfere with other hormones of the hypothalamus-pituitary-gonadal axis and therefore, cannot be considered, responsible for endocrine disorders during treatment with cimetidine.

Administration, Oral↗

Effects of 17 beta-estradiol, synthetic estrogens, and antiestrogens on prolactin secretion, nuclear translocation of pituitary estrogen receptor and on progesterone receptor levels in rat pituitary, hypothalamus and uterus.

Estrogen-receptor and progesterone-receptor values were studied following repeated application of estrogens and/or the antiestrogen tamoxifen. Nuclear estrogen-receptor contents of the pituitary as well as serum prolactin levels and uterus weight were increased by treatment with 17 beta-estradiol and synthetic estrogens DM-EE2 (1,3 diacetoxy-17 alpha-ethinyl-7 alpha-methyl-1,3,5(10)-estratrien-17 beta-ol) and DB-EE2 (1,3 dibenzoyloxy-17 alpha-ethinyl-7 alpha-methyl-1,3,5(10)-estratrien-17 beta-ol). Tamoxifen also increased pituitary estrogen receptor values, but no stimulation of serum prolactin levels was found. Tamoxifen decreased estradiol stimulated uterus weight, but had no repressor effects on serum prolactin levels. Progesterone receptor levels were stimulated in the pituitary by repeated injection of 17 beta-estradiol, DM-EE2 and DB-EE2 and to a smaller degree by tamoxifen. The stimulation of progesterone receptor levels by estrogen was greater in the pituitary than in the hypothalamus and uterus. The present data combine to suggest differences in metabolic and/or cellular events following stimulation with estrogens of different biological activities.

Animals↗

[Value of prolactin determination in oligozoospermia].

Serum levels of prolactin were determined in 181 patients with idiopathic oligozoospermia, in order to find out a possible interference of hyperprolactinemia and disturbed spermatogenesis. In 4 cases hyperprolactinemia was found. Suppression of prolactin levels by bromocriptine in those cases did not result in an increase of spermatogenetic activity. From these data it can be concluded that hyperprolactinemia plays no significant role in idiopathic oligozoospermia. The value of determination of serum levels of prolactin remains questionable.

Humans↗

Estrogen interaction with the anterior pituitary of female rats: Differential cytosol binding, nuclear translocation and stimulation of RNA synthesis by 17 beta-estradiol and tamoxifen.

The interaction of tamoxifen (trans-1-(rho-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene) with the cytosol estrogen receptor of the anterior pituitary of female rats was studied. No differences were recorded between incubations of cytosol samples with 17 beta-[3H]estradiol performed in the presence of absence of unlabeled 17 beta-estradiol and tamoxifen, respectively, thus suggesting that these interactions were at common receptor sites and excluding possible cooperative interactions. Competition experiments and Scatchard plot analysis of saturation experiments add further evidence for common receptor sites. A dissociation constant for tamoxifen of Kd - 2 nM was recorded. Tamoxifen was found to be bound to a moiety sedimenting the 4-5 S region, on a 6-24% linear sucrose density gradient at low salt concentrations, whereas 17 beta-estradiol sedimented in the 8-9 S area. These data suggest possible conformational changes of the receptor in the presence of tamoxifen. Furthermore, nuclear estrogen receptor levels remained elevated for at least 80 h after the application of tamoxifen alone or in a combination with 17 beta-estradiol, and a concomitant inhibition of cytosol receptor replenishment was noted. Tamoxifen and 17 beta-estradiol, respectively, were found to stimulate progesterone receptor levels when applied through 5 days. Tamoxifen plus 17 beta-estradiol administration elevated progesterone receptor contents above those found for each of the two compounds alone. On the other hand, tamoxifen enchanced the 17 beta-estradiol-induced prolactin serum levels, but did not stimulate prolactin serum levels by itself. These data combine to suggest that tamoxifen interacts with common estrogen receptor sites at the rat anterior pituitary.

Animals↗

[Oestrogen receptors and prognosis in breast cancer].

The determination of oestrogen receptors seems to be of prognostic value in the radically-operated breast cancer patient. Patients with negative receptor values exhibit early recurrence in a significantly higher percentage of cases than those with positive values. The prognostic implications of oestrogen receptor determination seem to be even higher than an assessment of axillary lymph node involvement. In metastatic breast carcinoma a correlation exists between response to hormonal therapy and receptor assay. The clinical implications for therapeutic management are discussed.

Adult↗

[Hormone receptors in research and their clinical application (author's transl)].

Experimental investigations and clinical studies stress the importance of hormone receptors in basic research and clinical investigation. The study of LH-RH receptors in the anterior pituitary of rats resulted in the possible use of LH-RH analogues as competitive inhibitors of the releasing hormone. This resulted in the development of a new concept of fertility control. The investigation of steroid hormone receptors in the anterior pituitary of rats provided a basis for the mechanism of action of steroids in modulating the release of gonadotropins and prolactin from the adenohypophysis. The determination of cytoplasmatic oestrogen-receptor and progesterone-receptor levels, combined with the estimation of the nuclear oestrogen-receptor content allows an improved selection of patients for endocrine therapy of breast tumours. Our results on the investigation of steroid receptors in the human endometrium suggest that receptor assays are of prognostic value and provide a guide for selecting patients with cancer of the body of the uterus for adjuvant hormone therapy. In addition, the present data combine to suggest that receptor assays may be useful in other endocrine diseases and in cases of unexplained sterility.

Animals↗

[Serum prolactin levels during therapy of prostatic cancer with oestradiol-17 beta-undecylate and cyproterone acetate (author's transl)].

Sixteen patients aged from 50 to 79 years with inoperable prostatic cancer were allocated at random to treatment either with 300 mg cyproterone acetate at weekly intervals or with 100 mg oestradiol-17 beta-undecylate every month. Blood samples were taken before treatment and at monthly intervals during the 6-month period of treatment. Serum prolactin levels were determined by a double-antibody radioimmunoassay. Basal serum levels of prolactin were 7.76 +/- 4.84 ng/ml and 9.50 +/- 4.32 ng/ml in the two groups of patients before therapy with oestradiol-17 beta-undecylate or cyproterone acetate, respectively. These pretreatment serum prolactin levels were statistically indistinguishable. Serum prolactin levels did not rise significantly during the first 5 months of treatment with cyproterone acetate, although an increase in prolactin was found in the sixth months of therapy with the antiandrogen. On the other hand, oestradiol-17 beta-undecylate raised serum prolactin levels significantly already after one month of treatment and the mean values were significantly higher than in the antiandrogen-treated group. These data combine to suggest cyproterone acetate as a suitable alternative to oestrogens in the therapy of inoperable prostatic cancer.

Aged↗

Nuclear translocation of estrogen-receptor complex and stimulation of RNA synthesis by estrogens of different biological potencies in the female rat pituitary.

Stimulation of RNA synthesis and of nuclear translocation of estrogen-receptor complexes was investigated in isolated nuclei of anterior pituitaries of castrated female rats after injection with estrogens of different biological potencies. The assay system for the estimation of total RNA synthesis was validated and data suggest that incorporation of [3H]UMP into acid-precipitable material is consistent with RNA synthesis. An increase in RNA synthesis was seen 30 min after application of either 17 beta-estradiol, estriol or 1,3-diacetyl-17 alpha-ethinyl-7 alpha-methyl-1,3,5,(10)estratriene-17,3-ol (DMEE). RNA synthesis was maximal 90 min after estrogen application. Thereafter, RNA synthesis decreased slowly and reached pretreatment levels 3, 8 and 30 h after application of estriol, 17 beta-estradiol and the diacetyl derivative of ethinyl-estradiol, respectively. All estrogens were found to stimulate rapidly nuclear translocation of estrogen-receptor complexes. Peak levels of nuclear receptor contents were reached 30 min after administration of estrogens. A concomitant depletion of cytosol receptor levels was noted. Nuclear retention of estrogen-receptor complexes paralelled duration of enhanced RNA synthesis and correlated with biological potencies of the steroids. Data of present experiments combine to suggest that long-term nuclear retention is a requisite for expression of biological activity of estrogens at the anterior pituitary. Furthermore, the degree of biological activity seems to be associated with duration of stimulation of RNA synthesis, amount of estrogen-receptor complexes translocated to the nucleus, and duration of nuclear retention.

Animals↗

[Androgen therapy of impotentia coeundi in elderly men. Psychological and endocrinological investigations (author's transl)].

The aim of the present investigation was to assess impotence in elderly men by clinical, endocrinological and psychological examinations. Altogether 17 patients were treated in a double-blind study with placebo or 75 mg mesterolone per day over 8 weeks. The subjects were aged between 45 and 60 years and suffered from impotentia coeundi. No differences in serum LH and testosterone levels were noted between the start and end of therapy. Similarly, serum LH and testosterone levels in these patients did not differ from those in a control group. These results suggest that the "male climacteric" need not necessarily the associated with alterations in hormone parameters. On the other hand, mesterolone therapy resulted in an improvement in potency and other psychosomatic parameters.

Androgens↗

[Estrogen and androgen receptors in patients with acne vulgaris (author's transl)].

Fifteen male and 9 female patients between 14 and 41 years of age who suffered from acne were included in this study. Sixteen endocrine normal males and 27 females were used as controls. Skin and venous blood samples were taken from both normal and acne patients. Specific estrogen and androgen receptor levels were assayed under conditions resulting in the estimation of unoccupied receptor levels, and the charcoal technique was utilized. Testosterone serum levels were determined by radioimmunoassay. No estrogen receptors could be found in the normal skin. Of the male and female acne patients 93 and 78%, respectively, were estrogen receptor-positive, and their levels were between 11 and 275 fmol/mg cytosol protein. On the other hand, 31 and 48%, respectively, of the male and female acne patients were androgen receptor-positive, and their receptor levels were between 35 and 213 fmol/mg cytosol protein. A correlation of r = 0.71 between estrogen and androgen receptor levels was noted in the female subjects, but no correlation was found in the male subjects. A correlation between testosterone serum levels and androgen receptor levels of r = 0.77 and r = 0.66, respectively, was noted in the female and male acne patients. The results of the present investigation suggest that androgen receptor levels play an important role in acne patients with normal testosterone serum levels. In addition, the presence of estrogen receptor levels in acne patients indicates a possible therapy by anti-estrogens or estrogens.

Acne Vulgaris↗

HPL and estriol serum levels of placental perfusion as indexes of placental function in EPH gestosis and placental insufficiency.

62 patients with EPH gestosis and 64 subjects suffering from placental insufficiency were monitored with estimation of placental perfusion and determination of radioimmunoassayable serum levels of human placental lactogen (HPL) and estriol. The utero-placental blood flow was measured by quick intravenous administration of 0.25-1.0 mCi of (113m)In, and the radioactivity uptake curve was evaluated by a computer program. Good correlation between perfusion type of serum levels of HPL and estriol was recorded. The present data combine to suggest that the recording of utero-placental blood flow is valuable aid in the diagnostic and prognostic evaluation of high-risk pregnancies.

Blood Circulation↗

First-trimester serum prolactin levels in normal and complicated pregnancies.

Subfractional activities and some properties of beta-glucuronidase were studied at different ontogenetic stages of the human placenta. Maximum activity was localized in normal pregnancies rose from 13.58 ng/ml in the 6th week to 52.46 ng/ml in the 15th week of gestation with marked individual variability. In tubal pregnancies, serum hPRL was low and did not increase over a period of 3--6 weeks. In women with spontaneous abortion, hPRL levels often were in the normal range with a drop only immediately prior to expulsion of the fetus. In patients with missed abortion the drop in serum prolactin levels seemed to coincide with the death of the conceptus.

Abortion, Missed↗

Pituitary and hypothalamic action of progestagens in castrated female rats.

Different doses of progesterone, D-norgestrel and delta 15-D-norgestrel were injected subcutaneously for 7 days to female rats castrated 7 days prior to the experiments. One day after the last steroid injection a i.p. LH-RH test was performed, blood samples were collected by heart puncture and serum levels of r-LH and r-FSH were estimated by radioimmunoassay. LH-RH serum levels were determined in progestagen treated control groups by an anterior pituitary cell culture bioassay. Dose dependent inhibitory effects of steroids on LH-RH stimulated gonadotropin release were observed and a dissociation of r-LH and r-FSH serum levels was found. The modulatory influence of progestagens used in this study on LH-RH provoked gonadotropin release correlated with their biological efficiency evaluated in the Clauberg test. Progesterone, D-norgestrel and delta 15-D-norgestrel treatment had no significant effects on basal r-LH levels, but LH-RH provoked r-LH levels were higher than in the control animals. Progesterone and D-norgestrel suppressed basal as LH-RH stimulated r-FSH levels, whereas delta 15-D-norgestrel showed a complex influence on r-FSH secretion. A progestagen stimulated rise of LH-RH serum levels was found and indicated an additional effect of these hormones at the hypothalamic level. These data suggest the action of progestagens at various levels of the hypothalamus-pituitary axis.

Animals↗

[Basal and LH-RH-stimulated gonadotropin release after transport stress in male rats].

A total of 120 male rats of the Sprague-Dawley-strain (6 weeks old) were used in this experiment. 5 groups of 12 animals each were treated intraperitoneally with 200 ng gonadotropin releasing hormone (LH-RH) per animal. 30 minutes later blood was sampled by heart puncture. Group I were animals without transport, group II immediately after, group III one day, group IV one week and group V six weeks after a standardised transport. Another 5 groups were subjected to the same protocol but received saline i.p. instead of LH-RH. Serum levels of LH and FSH were estimated by radioimmunoassay. LH and FSH serum levels could be stimulated by LH-RH in all groups. A significant rise of basal and LH-RH stimulated LH levels was observed until the first day after transport. Thereafter a drop was registered. No consistent patterns of basal as well LH-RH stimulated FSH-levels were noted. These data combine to suggest an elevation of LH-RH secretion as response to the stress. This results in a sensibilisation of the pituitary to exogenous LH-RH.

Animals↗

Modulation of LH-RH stimulated gonadotropin release by progestagens and 17 beta-estradiol in primary pituitary cell culture.

Simple trypsination procedure for rat anterior pituitary gland which permits a high yield of viable cells was described. Primary cell cultures set up by this method was characterized for their ability to release gonadotropic hormones into the culture medium with or without stimulation by hypothalamic extracts and a synthetic LH-RH, maximal sensitivity to the latter being found at 3--4 days after plating. Gonadotropin secretion was maximal after 4 hr of incubation with LH-RH, its maximal effective dose (ED50) being between 10(-11) and 10(-10) mol 1(-1). Such a dose stimulated rLH release into the medium by a factor of about 6 and rFSH secretion by a factor of 3 over controls. The preincubation of cultures wih progesterone, D-norgestrel and delta 15-D-norgestrel resulted in a progestagen dose-dependent desensitization of the cell cultures against LH-RH for both gonadotropic hormones. This effect of progestagens was found to be time-dependent and maximal inhibition was found after 12-20 h. However, more effective inhibition of LH-RH stimulated rLH release was caused by preincubation with cycloheximide suggesting the importance of protein synthesis in the course of LH-RH augmented gonadotropin release. A dissociation of sensitivity of cultured cells against LH-RH concerning their rLH and rFSH release was also found after preincubation with a mixture of progesterone and estradiol. Present data and previous observations strongly suggest the modulatory influence of steroid hormones on LH-RH provoked gonadotropin release at the pituitary level.

Animals↗

LH patterns during clomiphene-induced menstrual cycles.

A total of 409 sterility patients with amenorrhea classified as group II according to the WHO rating scheme were treated with a daily dose of 100 mg of Clomiphene daily for five days in 452 cycles. In addition, 300 infertile subjects with spontaneous cycles (375), but with slight irregularities in the lengths of cycles were included in this investigation as control group. Daily LH serum levels were monitored by rapid solid-phase coated tube RIA. 61.87% of LH single peaks, 28.53% of plateau peaks and 0.53% of double peaks were registered in spontaneous cycles. Similarly, 60.28% single peaks, 23.67% plateau peaks and 0.66% double peaks were registered in Clomiphene-induced cycles. Highest rate of LH plateau and single peaks were found 4 to 6 days and 5 to 7 days, resp., after the end of Clomiphene therapy. No LH peaks were found in 9.07% of spontaneous cycles and in 15.39% of Clomiphene-induced cycles. Data combine to suggest that timing of ovulation by a rapid LH radioimmunoassay is a valuable aid in consulting infertile couples. Failures of patients to conceive must be due to causes other than incorrect timing of ovulation.

Clomiphene↗

[Prognostic value of estrogen receptors in breast cancer (author's transl)].

One hundred and ninety-one patients with operable breast cancer were followed for up to 34 months after operation and the early recurrence of disease was noted in relation to the presence or absence of estrogen receptor. Recurrence rates were significantly higher in patients whose tumors did not contain receptors than in those whose tumors did. The response to cytotoxic chemotherapy in patients with advanced breast carcinoma seems to be independent of the presence of E2R in cancer tissue.

Breast Neoplasms↗

[Hormonal and functional parameters in hyperprolactinaemia (author's transl)].

58 women with raised serum prolactin levels and normal hypophyseal-X-ray parameters were subdivided into three groups according to the serum prolactin level (16 to 40, 41 to 80, greater than 80 ng/ml). In addition to the determination of LH, FSH, oestradiol, progesterone and testosterone in the serum and thyroid diagnostic procedures the following hormonal tests were performed: 1. response to gestagen; 2. response to clomiphene; 3. Gn-RH-test for hypophyseal function; 4. ovarian response to administered gonadotropins (only in cases with prolactin levels greater than 80 ng/ml). The grade of menstrual cycle disorders depends on the severity of the observed hyperprolactinaemia. Slight disorders like luteal phase insufficiency, anovulatory cycle and oligomenorrhoea are associated with low- or medium-grade hyperprolactinaemia. Mainly secondary, but also primary amenorrhoea is found in cases with higher serum prolactin levels (greater than 80 ng/ml). In these cases the hypophyseal response to Gn-RH is frequently found (61%) to be negative and, moreover, the ovarian response to administered gonadotropins seems to be diminished. Increasing HPRL levels often appear to be associated with a negative response to the other above-mentioned tests.

Clomiphene↗