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Biomedical subjects

C Bieglmayer

Publications and source records attributed to C Bieglmayer.

At least 127 records · Page 7Linked to original sources
PubMed1981

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↗
PubMed1980

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↗
PubMed1980

[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↗
PubMed1980

[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↗
PubMed1980

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↗
PubMed1980

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↗
PubMed1980

[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↗
PubMed1980

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↗
PubMed1980

[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↗
PubMed1979

Mutant and immunochemical studies on the involvement of cytochrome b5 in fatty acid desaturation by yeast microsomes.

The involvement of cytochrome b5 in palmitoyl-CoA desaturation by yeast microsomes was studied by using yeast mutants requiring unsaturated fatty acids and an antibody to yeast cytochrome b5. The mutants used were an unsaturated fatty acid auxotroph (strain E5) and a pleiotropic mutant (strain Ole 3) which requires either Tween 80 and ergosterol or delta-aminolevulinic acid for growth. Microsomes from the wild-type strain possessed both the desaturase activity and cytochrome b5, whereas those from mutant E5 contained the cytochrome but lacked the desaturase activity. Microsomes from mutant Ole 3 grown with Tween 80 plus ergosterol were devoid of both the desaturase activity and cytochrome b5, but those from delta-aminolevulinic acid-grown mutant Ole 3 contained cytochrome b5 and catalyzed the desaturation. The cytochrome b5 content in microsomes from mutant Ole 3 could be varied by changing the delta-aminolevulinic acid concentration in the growth medium, and the desaturase activity of the microsomes increased as their cytochrome b5 content was increased. The antibody to yeast cytochrome b5, but not the control gamma-globulin fraction, inhibited the NADH-cytochrome c reductase and NADH-dependent desaturase activities of the wild-type microsomes. It is concluded that cytochrome b5 is actually involved in the desaturase system of yeast microsomes. The lack of desaturase activity in mutant Ole 3 grown with Tween 80 plus ergosterol seems to be due to the absence of cytochrome b5 in microsomes, whereas the genetic lesion in mutant E5 appears to be located at ther terminal desaturase.

Cytochromes↗
PubMed1979

Hormone serum levels and hormone receptor contents of endometria in women with normal menstrual cycles and patients bearing endometrial carcinoma.

Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (HPRL), 17 beta-estradiol (E2) and progesterone (P) were estimated in 46 subjects with normal menstrual cycles in whom hysterectomies were performed. Estrogen (ER) and progesterone receptor (PgR) levels in endometrial samples of these patients were estimated, and histological dating of the cycle day was carried out. Similarly, hormone serum levels and ER as well as PgR were estimated in 17 patients with endometrial carcinoma. No correlation between LH, FSH, HPRL and ER as well as PgR was noted in the normal subjects. Correlation between P and ER was observed in this group. Parallel variations between E2 and PgR were recorded in the normal females. In the carcinoma group no correlations between hormone serum levels and receptor contents were found, but ER and PgR correlated with each other. Receptor levels was highest in the well-differentiated group of endometrial carcinoma. The present experiments provide a rationale for progestagen therapy of carcinoma of the endometrium.

Endometrium↗
PubMed1979

Transformation and translocation of 17 beta-estradiol receptor in rat pituitary.

The association of 17 beta-(3H)-estradiol with its pituitary cytosol receptor is described. The transformation products of this 8 S receptor complex at high salt concentration was analyzed by 5-20% linear sucrose gradients. KCl was found to reversibly convert the 8 S moiety into a 4-5 S species. The transformation by CaCl2 and trypsin was found to be irreversible. In addition, the nuclear translocation of the estrogen-receptor complex was investigated in vitro. Translocation was found to be temperature-dependent, since a 6 S nuclear receptor complex could be extracted from crude nuclei only after incubation of whole pituitaries at 37 degrees C and not at 4 degrees C incubation temperature. Similarly, a 6 S species was found upon sucrose gradient analysis of nuclear extract after a cell free incubation of isolated nuclei and cytosol with 17 beta-(3H)-estradiol. Maximal translocation was observed in this in vitro system within 60 to 90 min, resulting in a concomitant loss of cytosol receptor. The present data combine to suggest that nuclear translocation resembles one of the early events involved in the molecular action of estrogen at the pituitary level.

Animals↗
PubMed1978

Maturation of 17 beta-estradiol binding protein in the hypothalamus and anterior pituitary of male rats.

Levels of estrogen binding proteins in the cytosol of hypothalamic and pituitary tissue of male rats at different ages were estimated. Two classes of estrogen binding sites were detected in 13 and 20 days old animals. The number of high affinity estrogen binding sites (K = ca. 2 x 10(-10) mol) of the hypothalamus was slightly larger in 13 days old animals, then decreased to constant levels at the age of 20 days and no changes were observed thereafter. Levels of low affinity binding sites of the hypothalamus (K = ca. 5 x 10(-9) mol) decreased with age and were no longer detectable in 30 days old animals. Similarly, a decrease of low affinity estrogen binding sites with age was recorded for pituitary cytosol samples and this class of receptor sites was no longer observable in 30 days old male rat. At 13 days high levels of high affinity 17 beta-estradiol binding protein was registered and minimal numbers of binding sites were found at 20, 30 and 40 days. Thereafter, the levels remained constant until 100 days and were similar to values observed in the 13 days old male animals. Apparent affinity constants of two classes of binding sites in hypothalamus and pituitary were similar...

Aging↗