Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anorexia nervosa is associated with several abnormalities in GH secretion elicited by different stimuli. To investigate the precise mechanism of this alteration, GHRH was administered to 14 women: a group of eight anorexia nervosa patients in the acute phase of their illness and a control group of six age-matched volunteers. As patients with anorexia nervosa have chronic low oestrogen values, the volunteer women of the control group underwent a second GHRH test after pretreatment with the oestrogen receptor blocker tamoxifen. GHRH 1-29 (1 microgram/kg i.v.) induced a GH peak (mean +/- SEM) of 28.2 +/- 5.1 ng/ml (GH ng/ml x 2 = mU/l) at 30 min in the anorectic patients. This value was no different from the GHRH-stimulated GH peak in the control women (28.1 +/- 10.0 ng/ml). Tamoxifen pretreated women had a GH peak after GHRH of 35.6 +/- 9.7 ng/ml, not significant versus control test. Compared with the control group, oestrogen levels were significantly lower in anorectic patients and higher in tamoxifen-treated women. GHRH administration induced a small PRL peak at 15 min that was similar in the three groups tested. After this 15 min peak, PRL in both anorexic and tamoxifen-treated women returned toward basal values steadily. However, in untreated control women a second PRL peak was evident at 60 min. In conclusion, GHRH-induced GH secretion in anorexia nervosa patients was similar to that in control subjects and in controls under oestrogen receptor blockade.
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PMID:Growth hormone and prolactin secretion after growth hormone-releasing hormone administration, in anorexia nervosa patients, normal controls and tamoxifen-pretreated volunteers. 289 60

The affinity of danazol for oestrogen, androgen and progesterone receptors in human endometrium and myometrium was determined, to study the mechanism of action of this drug in the treatment of endometriosis. The ability of danazol to combine with each of the three types of receptor was similar in both endometrium and myometrium. The capacity of danazol to compete with oestradiol-17 beta for the oestrogen receptor was very low (1.72 +/- 0.48 X 10(-3%) cross reaction, mean +/- SEM) and danazol, at the maximum concentration used, was unable to saturate the receptor; but danazol's ability to compete with progesterone for its receptor was considerably higher (8.41 +/- 1.65% using progesterone, 1.95 +/- 0.41% using R5020) and was saturable. Danazol was also able to displace dihydrotestosterone from the cytosol androgen receptor (6.29 +/- 1.82% cross reaction). The association constant of oestradiol for the endometrial and myometrial oestrogen receptors was 2.19 X 10(9)M-1 and 7.45 X 10(9)M-1 respectively, while that of progesterone and dihydrotestosterone for their receptors was similar in endometrium and myometrium (mean 0.25 +/- 0.06 X 10(9) M-1 and 3.62 +/- 1.67 X 10(9) M-1 respectively). Using R5020, the association constant for the myometrial progesterone receptor was 2.50 +/- 0.73 X 10(9) M-1. We conclude that, in view of the high circulating levels of danazol present in patients being treated for endometriosis, it is possible that danazol may bind to, and partly saturate, endometrial and myometrial oestrogen, progesterone and androgen receptors during treatment. An explanation may thus be provided for some of the diverse actions of this drug.
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PMID:The interaction of human endometrial and myometrial steroid receptors with danazol. 662 94

The ligand specificity of progesterone and oestrogen receptors in the uteri of four nonpregnant, nonlactating African elephants, killed during routine culling in the Kruger National Park, were determined. The mean (+/-SEM) Kd values of the oestrogen (0.18 +/- 0.019 x 10(-9) mol l-1, n = 12) and progesterone (0.22 +/- 0.025 x 10(-9) mol l-1, n = 12) receptors were essentially similar when [3H]promegestone was used as radioligand in the progesterone receptor assays. However, when [3H]progesterone was used as radioligand, the progesterone receptor exhibited a significantly higher Kd value (1.03 +/- 0.132 x 10(-9) mol l-1, n = 12) than that of the oestrogen receptor. The use of the different radioligands did not significantly affect the quantitative values obtained for the progesterone receptor. Both the oestrogen and the progesterone receptors displayed a high ligand specificity. The 5 alpha-reduced metabolites of progesterone exhibited a high relative binding affinity for the progesterone receptor (5 alpha-pregnane-3,20-dione: relative binding affinity = 43%; 5 alpha-pregnane-3 alpha-ol-20-one: relative binding affinity = 20%) but the synthetic antiprogestin RU 486 did not compete successfully with progesterone in competitive binding studies. However, norethindrone (relative binding affinity = 293%) competed successfully for binding to the progesterone receptor, and may have some potential in the future development of a technique to control reproductive output in the African elephant.
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PMID:Ligand specificity of uterine oestrogen and progesterone receptors in the subadult African elephant, Loxodonta africana. 915 28

The effects of the short-term pre-operative administration of tamoxifen (TAM, 20 mg once daily) on the tumor levels of steroid receptors and the nuclear proliferation Ki-67 antigen, were investigated in 32 elderly patients with hormone-sensitive, operable primary breast cancer by means of fine-needle aspiration biopsy (FNAB). The FNAB smears before (pre-TAM) and after six weeks of treatment (post-TAM) were stained immunocytochemically in order to obtain an H-score for steroid receptors, and the percentage of cellular nuclei containing Ki-67. The mean oestrogen receptor (ER) score between the pre- and post-TAM specimens fell from 181.2 9.7 ( SEM) to 148.1 7.9 (Wilcoxon's matched-pairs signed-rank test, p=0. 01) and there was also a significant decrease in both the mean progesterone receptor (PgR) score (178.4 10.6 vs 148.5 10.6; p=0.01) and mean Ki-67 index (8.2% 1.2 vs 4.9% 0.9; p=0.0002). The reliability of FNAB as a sampling method was checked by comparing the results of the immunocytochemical assay (ICA) of the post-TAM biopsies with those of the immunohistochemical assay (IHA) of the corresponding excised tumors. There was a positive correlation between the ICA and IHA scores: ER (Spearman's correlation coefficient, rho=0.66, p<0.001), PgR (rho=0.84, p<0.001) and Ki-67 (rho=0.96, p<0.001). We conclude that the sequential use of FNAB is a reliable means of assessing the behaviour of within-tumor biomarkers during endocrine therapy.
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PMID:Effects of short-term pre-operative tamoxifen on steroid receptor and Ki-67 expression in primary breast cancer: an immunocytochemical study. 949 46

The mechanism by which oestrogen and hormone replacement therapy (HRT) maintain bone mass in women is still unclear. It has previously been shown that cells of osteoblast lineage in vivo, particularly osteocytes, express oestrogen receptor alpha (ERalpha). Nevertheless, it is still debatable whether oestrogen and the ovarian steroids have a direct affect on osteocytes. If they could regulate osteocyte ERalpha expression, this would be strong evidence for the involvement of these cells in the hormonal regulation of bone mass. This study therefore aimed to compare bone biopsies from women who were replete with ovarian steroids (pre-ovariectomy or post-HRT) with those from the same women when hormone-deficient (post-ovariectomy or pre-HRT) for cellular localization of ERalpha protein or mRNA expression by indirect immunofluorescence, or by in situ hybridization combined with reverse transcriptase-polymerase chain reaction (IS-RT-PCR) respectively. Image analysis showed that proportions of osteocytes positive for immunodetectable ERalpha were higher in hormone-replete than in hormone-deficient women (25+/-SEM 3 per cent, 12+/-SEM 4 per cent, respectively; n=5), with similar but non-statistically significant changes in osteoblasts. This was observed even when HRT was commenced 18 years after menopause. In contrast, grain volume/unit cell area of osteoblast mRNA signal was markedly higher when hormone-deficient (0.055+/-0.01) than when hormone-replete (0.016+/-0.004), with similar but non-significant differences in osteocytes. This preliminary study indicates up-regulation of osteocyte ERalpha protein by ovarian steroids in these patients, which is accompanied by decreased osteoblast ERalpha mRNA expression, providing further evidence for the involvement of osteocytes in the regulation of skeletal structure by ovarian steroids.
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PMID:Effect of ovarian steroid deficiency on oestrogen receptor alpha expression in bone. 1041 99

In western countries, osteoporosis affects at least 1 in 12 of all adult males and a third of osteoporotic men have idiopathic disease (MIO). Both oestrogen and testosterone are now known to be important to the male skeleton. As normal oestrogen levels have been found in younger MIO cases, it is hypothesized that, in bone, their responses to gonadal steroids may be defective, through impaired receptor expression. This study therefore compared oestrogen receptor (ER)-alpha and androgen receptor (AR) expression, by indirect immunofluorescence and semi-quantitative image analysis, in undecalcified fresh frozen bone sections from MIO patients (33-56 years), age-matched control men (n=7), and, for reference, ovarian steroid-replete (n=7) and -deficient women (n=6). In normal men, 23%+/-SEM 6% osteoblasts and 14%+/-SEM 2% osteocytes expressed ERalpha protein, similar to hormone-replete women. Although receptor expression decreased in hormone-deficient women, loss of ERalpha protein in MIO patients was more severe (1%+/-SEM 0.5% osteocytes, 2%+/-SEM 1% osteoblasts expressed receptor). In all four groups, there was little osteocyte AR expression, but in the women, a proportion of osteoblasts were receptor-positive. Deficient osteoblast and osteocyte ERalpha protein expression could explain the bone loss in these MIO patients.
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PMID:Preliminary report of impaired oestrogen receptor-alpha expression in bone, but no involvement of androgen receptor, in male idiopathic osteoporosis. 1095 5

In the bovine reproductive tract, the uterine tube is the critical site for a series of events required for fertilization and early embryonic development. In previous studies, a defined category of subfertile heifers, repeat-breeder heifers (RBH), has presented peri-oestrual disturbances (deviating hormone patterns and follicular dynamics) and uterine maternal-embryonic asynchrony. The present study aimed to investigate if tubal function was also affected, by determination of differences in the morphology of the tubal lining epithelium of RBH (n = 4) in comparison to controls (n = 6) during standing oestrus, studied by light and electron microscopy (SEM/TEM), and relate this to steroid hormone concentrations and receptor distribution in the target tissues. Tissue distribution of oestrogen receptor alpha (ERalpha) and progesterone receptor B (PRB) was quantified using immunohistochemistry. In particular, secretory cells differed in appearance between RBH and controls. The cells were less lumen protruding, microvilli were fewer and smaller and secretory granules in the apical cytoplasm were more numerous in RBH. Furthermore, the tubal epithelium was conspicuously coated with amorphous material. Morphological differences between categories were not explained hormonally or by steroid receptor distribution, except in two heifers from which uterine tubes were obtained after the luteinizing hormone (LH) surge. The isthmic PRB : ERalpha ratio was twice as high in the RBH than in the control. The deviating ultrastructure found in RBH, before and after the LH surge, might influence the tubal microenvironment with effects on gamete transport and final maturation and early embryonic development. The present study confirms that previously recorded perturbations in reproductive physiology in RBH are also manifested in the uterine tube, mainly by a deviating ultrastructure of the lining epithelium.
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PMID:Deviant peri-oestrual hormone patterns affect the epithelium of the uterine tube in repeat-breeder heifers. 1261 90