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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most widely studied steroid hormone responsive cancers are those of the prostate, endometrium and mammary endothelium and the leukaemias. Steroids may in some cases be involved in tumour initiation, and they induce critical events in the malignant 'progression' of these cancers once they develop (after exposure to carcinogens, for example). This paper focuses on the role of the oestrogen receptor as a trigger of cellular growth and invasiveness and as modulator of growth factor secretion in human breast cancer. Growth factor secretion may be a common final pathway of diverse tumorigenic stimuli in a variety of cancers. The finding of external growth control mechanisms suggests possible new ways of therapeutic intervention in breast cancer.
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PMID:Hormonal control of human breast cancer cell lines. 355 86

A cytosolic oestrogen receptor from baboon endometria was detected and partially characterized. The apparent dissociation constant for oestradiol was 1.5 x 10(-10)--4 x 10(-10) mol/l. Steroids that competed with the [3H]oestradiol binding to the receptor were oestradiol and ethynyloestradiol greater than oestriol greater than oestrone; progesterone, testosterone and corticosterone were not competitors. The [3H]oestradiol-receptor complexes migrated as a 3-3.5S peak during sucrose density-gradient centrifugation when endometrial samples were taken during either the proliferative or the secretory phase. A 7S peak was observed for samples taken at the period of ovulation. A [3H]oestradiol exchange technique was used to detect changes in the receptor concentration during the menstrual cycle. This concentration which was high during the early follicular phase fell sharply before the ovulatory peak of ovarian oestrogens. It remained at a base level during the early secretory phase and then rose during the last days of the cycle to the same concentration as that measured at the beginning of the cycle.
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PMID:Oestrogen receptor in the baboon endometrium: cytosolic receptor, detection, characterization and variation of its concentration during the menstrual cycle. 736 69

Steroids have the ability to alter adipose tissue distribution. Controversy exists as to whether these effects of sex hormones (oestrogen, progesterone and testosterone) on human adipose tissue are indirect or direct, as only very few studies have focused on steroid receptor status in human adipose tissue. In the present study, we reinvestigated steroid receptor status in human mature adipose tissue and human preadipocytes. Oestrogen, glucocorticoid and androgen receptors were found in human mature adipocytes from both women and men. The receptors were detected by ligand binding. Furthermore, the existence of the receptors was confirmed by demonstrating that adipocytes contained mRNA encoding the receptors. cDNA was generated using reverse transcriptase (RT) followed by polymerase chain reaction (PCR) amplification using specific primers (RT-PCR) for the specific steroid receptors. Adipocytes did not contain mRNA encoding the progesterone receptor (PR), and no progesterone binding was detectable in human adipocytes. Human preadipocytes contained glucocorticoid receptor (GR) mRNA and androgen receptor (AR) mRNA, whereas we were unable to detect oestrogen receptor (ER) mRNA and progesterone mRNA in human preadipocytes. In conclusion, oestrogen glucocorticoid and androgen receptors are present in mature adipocytes from subjects of both sexes, whereas adipocytes do not contain progesterone receptors. In preadipocytes, only glucocorticoid receptors and androgen receptors are present, whereas oestrogen receptors and progesterone receptors are not present.
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PMID:Identification of steroid receptors in human adipose tissue. 901 78

Steroids and related compounds are important in disease development and prevention, via steroid receptor-mediated and receptor-independent mechanisms. Interaction of endogenous oestrogens with the oestrogen receptor has unfortunate mitogenic effects in breast cancer. However, dietary consumption of non-steroidal weak oestrogens, such as the soy isoflavone phytoestrogens genistein and diadzein, is associated with a decreased breast cancer risk. This may arise in part from the suboptimal configuration induced in the transactivation helix of oestrogen receptor-beta.
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PMID:New advances in the understanding of the role of steroids and steroid receptors in disease. 1135 55

Two structurally related subtypes of oestrogen receptor (ER), known as alpha (ER alpha, NR3A1) and beta (ER beta, NR3A2) have been identified. ER beta mRNA and protein have been detected in a wide range of tissues including the vasculature, bone, and gonads in both males and females, as well as in cancers of the breast and prostate. In many tissues the pattern of expression of ER beta is distinct from that of ER alpha. A number of variant isoforms of the wild type beta receptor (ER beta 1), have been identified. In the human these include: (1). use of alternative start sites within the mRNA leading to translation of either a long (530 amino acids, hER beta 1L) or a truncated form (487aa hER beta 1s); (2). deletion of exons by alternative splicing; (3). formation of several isoforms (ER beta 2-beta 5) due to alternative splicing of exons encoding the carboxy terminus (F domain). We have raised monoclonal antibodies specific for hER beta1 as well as to three of the C terminal isoforms (beta2, beta 4 and beta 5). Using these antibodies we have found that ER beta 2, beta 4 and beta 5 proteins are expressed in nuclei of human tissues including the ovary, placenta, testis and vas deferens. In conclusion, in addition to the differential expression of full length ER alpha and ER beta a number of ER variant isoforms have been identified. The impact of the expression of these isoforms on cell responsiveness to oestrogens may add additional complexity to the ways in which oestrogenic ligands influence cell function.
Steroids 2002 Nov
PMID:Human oestrogen receptors: differential expression of ER alpha and beta and the identification of ER beta variants. 1239 95

The risk-benefit ratio of traditional postmenopausal hormone therapy is considered by many to be unacceptable. Low-dose oestrogen-progestin therapy (oral or non-oral and continuous or pulsatile) may have a better risk-benefit ratio, but this remains unproven. Steroids with selective tissue activation, such as tibolone, alleviate symptoms and protect against bone loss, but long-term safety data are lacking. Selective oestrogen receptor modulators (SERMs), such as raloxifene, prevent bone loss when used alone, and may soon be combined with oestradiol to treat symptoms and prevent osteoporotic fracture. Effects of SERMs on the cardiovascular system are currently being evaluated.
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PMID:Menopause: new therapies. 1279 52

Despite recent gains in our knowledge of the hormonal control of proliferation and differentiation in the rodent mammary gland, the factors regulating these processes in the human are poorly understood. We have developed a model in which intact normal human breast tissue is grafted subcutaneously into adult female athymic nude mice and treated with oestrogen (E) and/or progesterone (P) at human physiological serum levels. We have shown that (i) E and not P is the major epithelial cell mitogen in the adult non-pregnant, non-lactating breast, (ii) E induces progesterone receptor (PR) expression and (iii) PR expression is maximally induced at low E concentrations while a higher amount of E is required to stimulate proliferation. These data raised the question of whether one cell type demonstrated two different responses to the two different E concentrations or whether PR expression and proliferation occurred in separate cell populations. Using dual label immunofluorescence, we showed that steroid receptor expression and proliferation (Ki67 antigen) are detected in separate cell populations in normal human breast epithelium, and that cells expressing the oestrogen receptor-alpha (ERalpha) invariably contained the PR. We also reported that this separation between steroid receptor expression and proliferation observed in the normal human epithelium is disrupted at an early stage in breast tumourigenesis. One interpretation supported by our recent findings is that some ERalpha/PR-positive epithelial cells are quiescent breast stem cells that act as "steroid hormone sensors". Such hormone sensor cells might secrete positive or negative paracrine/juxtacrine factors dependent on the prevailing E or P concentration to influence the proliferative activity of adjacent ERalpha/PR-negative epithelial cells.
Steroids 2003 Nov
PMID:Steroid receptors and proliferation in the human breast. 1466 69

The purpose of this study was to investigate the role of the oestrogen receptor subtypes ERalpha and ERbeta in mediating the non-genomic effects of 17-beta-estradiol (E(2)) in two human endometrial cancer cell lines (RL95-2 and HEC-1A) expressing different levels of these receptor subtypes. Western blotting analysis using phosphorylation site-specific antibodies showed that physiological concentrations of E(2) rapidly (<20 min) activated PKCalpha, but not PKCdelta in the RL95-2 cell line. E(2) had no effect on PKCalpha or PKCdelta activity in the HEC-1A cell line and suppressed basal levels of PKA activity in both cell lines. PKCalpha activation coincided with its membrane translocation. ERalpha was detected in the RL95-2 cell line by Western blotting and RT-PCR but not in the HEC-1A cells, which did express ERbeta. A selective ERalpha agonist PPT had the same effect as E(2) on PKCalpha activation in the RL95-2 cells, but the selective ERbeta agonist DPN had no such effect. A 46kDa variant of ERalpha increased in abundance in the cell membrane within 20 min of E(2) treatment suggesting that ERalpha mediated the E(2) non-genomic effects on PKCalpha through the formation of a membrane associated signalling complex.
Steroids 2008 Oct
PMID:Membrane ERalpha-dependent activation of PKCalpha in endometrial cancer cells by estradiol. 1853 51

Despite effective treatments for oestrogen receptor-positive breast cancers, drug resistance is common and remains a significant clinical challenge. Targeting tumour vasculature by blockade of the vascular endothelial growth factor (VEGF) has proved successful in a variety of cancers. Phase III clinical trials of bevacizumab in combination with chemotherapy showed some efficacy in breast cancer. Concomitant targeting of the VEGF and oestrogen signalling pathways has the potential to provide enhanced therapeutic benefit in oestrogen receptor-positive breast cancer, and this strategy is under evaluation in clinical trials. This article summarises the rationale for this approach and clinical studies so far.
Steroids 2011 Jul
PMID:The combination of VEGF inhibitors and anti-oestrogen therapies in breast cancer. 2143 93

Considerable heterogeneity exists amongst oestrogen receptor positive (ER+ve) breast cancer in both its molecular profile and response to therapy. Attempts to better define variation amongst breast tumours have led to the definition of four main "intrinsic" subtypes of breast cancer with two of these classes, Luminal A and B, composed almost entirely of ER+ve cancers. In this study we set out to investigate the significance of intrinsic subtypes within a group of ER+ve breast cancers treated with neoadjuvant anastrozole. RNA from tumour biopsies taken from 104 postmenopausal women before and after 2 weeks treatment with anastrozole was analyzed on Illumina 48K microarrays. Gene-expression based subtypes and risk of relapse (ROR) scores for tumours pre- and post-treatment were determined using the PAM50 method. Amongst pre-treatment samples, all intrinsic subtypes were found to be present, although luminal groups were represented most highly. Luminal A and B tumours obtained similar benefit from treatment, as measured by the proportional fall in the proliferation marker Ki67 upon treatment (mean suppression=75.5% vs 75.7%). Tumours classified as basal and Her2-like showed poor reductions in Ki67 upon treatment. Residual Ki67 staining after two weeks remained higher in the Luminal B group. ROR score was significantly associated with anti-proliferative response to AI and with clinical response. These results suggest that in the short-term, Luminal A and B tumours may gain similar benefit from an AI but that the higher residual Ki67 level seen in Luminal B is indicative of poorer long term outcome.
Steroids 2011 Jul
PMID:Association between breast cancer subtypes and response to neoadjuvant anastrozole. 2144 51


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