Estrogen and antiestrogen binding to rat uterine and pituitary estrogen receptor: Evidence for at least two physicochemical forms of the estrogen receptor

Jasper, Thomas W.; Ruh, Mary F.; Ruh, Thomas S.

doi:10.1016/0022-4731(85)90001-9

Cited by 22 publications

(6 citation statements)

References 16 publications

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“…Moreover, we have reported heterogeneity in the distribution of the number of binding sites in distinct pituitary cells [11]. Several investigators have provided evidence for polymorphism in ER forms within pituitary cell types [16][17][18] as well as in different target tissues or cell lines [19][20][21][22][23]. Using affin ity labeling, we have previously shown that the major ER monomeric form was a 50,000-Mr truncated protein in the lactotrope and somatotrope populations from male rats, while gonadotrope-enriched populations presented an unique form of 65,000 Mr [18].…”

Section: Introductionmentioning

confidence: 99%

Sex- and Cell-Specific Expression of an Estrogen Receptor Isoform in the Pituitary Gland

Demay¹,

Tiffoche²,

Thieulant³

1996

Neuroendocrinology

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The presence of multiple monomeric forms has been described for the estrogen receptor (ER) in the pituitary gland. We analyzed ER mRNA forms in male and female rat pituitary. A single 6.2-kb ER mRNA species was detected in the male rat pituitary, whereas the female rat pituitary exhibited two ER mRNA forms of 6.2 and 5.5 kb, respectively. The 6.2-kb mRNA was present throughout the different stages of the estrous cycle, while the 5.5-kb mRNA appeared to be restricted to proestrus, suggesting an acute regulation of ER transcription at this stage. The 5.5-kb ER mRNA could be rapidly induced either by 17β-estradiol replacement in ovariectomized adult female rats or by priming immature rats with pregnant-mare serum gonadotropin. Using enriched cell populations, an inverse and strong correlation was established between the presence of the 5.5-kb ER mRNA form and the number of gonadotropes. Conversely, the localization of the 5.5-kb mRNA form was demonstrated in lactotrope populations. In order to elucidate the structural modifications in the transiently expressed ER mRNA, a series of reverse-transcriptase polymerase chain reaction amplifications was carried out using several pairs of primers corresponding to the entire ER-coding region. The data showed that no alternative splicing was occurring in the ER-coding region involving a potential role of either 3’- or 5’-untranslated regions. Thus, ER presents a 17β-estradiol-dependent transcriptional mechanism triggered on proestrous day and specific to the female lactotropes.

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Section: Introductionmentioning

confidence: 99%

Sex- and Cell-Specific Expression of an Estrogen Receptor Isoform in the Pituitary Gland

Demay¹,

Tiffoche²,

Thieulant³

1996

Neuroendocrinology

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“…The known physico-chemical diversity of ER may have functional consequences; different physico-chemical forms of ER have been described in rat uterus and pituitary, related to monomer and dimer formations (50). Differences in receptor binding by synthetic steroids also point to physico-chemical variation in ER from breast tumors and normal breast tissue.…”

Section: Discussionmentioning

confidence: 99%

Estrogen and Progesterone Receptors in Benign Breast Epithelium

Khan

1995

Breast Journal

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H Abstract: Estrogen and progesterone are necessary for lobulo-alveolar development of the human breast, and there is an abundance of epidemiologic literature implicating estrogen and possibly progesterone exposure as promoters of breast malignancy. The investigation of estrogen receptor (ER) and progesterone receptor (PgR) distribution in normal and benign breast tissue may be a measure of susceptibility of the tissue to these hormones. Earlier data from radioligand binding assays showed that benign breast tissue expressed little or no ER; newer immunohistochemical (IHC) methods have led to the investigation of benign breast tissue from at least 1243 women in 12 studies in the last 9 years. These show that the level of expression of ER and PgR in normal breast epithelium is significantly lower than in receptor positive carcinomas. lmmunostaining patterns for both receptors show a great deal of heterogeneity. There is general agreement that stromal and myoepithelial cells are negative for both ER and PgR. A growing body of evidence suggests that PgR is the dominant sex steroid receptor in the normal breast. Mean values for PgR positive cells in breast epithelium range from 24% to 29%; ER is positive by IHC in 3% to 15.6% of normal breast epithelial cells. No firm conclusions are possible as yet regarding overexpression in proliferative epithelium. There is agreement that the proportion of ER positive cells declines in the second half of the menstrual cycle, but there is no clear cut relationship between PgR positivity with the menstrual cycle. Oral contraceptive use appears to decrease the proportion of ER positive cells, and increase mammary epithelial proliferation. A recent case-control analysis of epithelial ER and f k~R status reports an association of ER positive benign epithelium with the presence of cancer in the Address correspondence and reprint requests to Seema A. Khan, M.D., 750 East A d a m Street, Syracuse, NY 13210, U.S.A. 0 1995 Blackwell Scrence lnc., 1075-122X/95/%10.50/0 The Breast]oumal, Volume 1, Number 4, 1995 251-261 breast. Future research should include a systematic quantitative analysis of receptor expression in epithelial proliferative lesions, and the longitudinal follow-up of women who have had receptor testing on benign breast tissue.strogen exposure is a well established risk factor for E breast cancer. Estrogen is a mitogen for breast cancer cells in culture, and also for normal breast epithelial cells in-vivo, although progesterone is an important mitogen for the normal breast (1,2). Estrogen effect on target tissues is mediated by its receptor, which is markedly overexpressed (relative to benign tissue) in about two thirds of invasive breast cancers. The study of estrogen receptor expression in normal and benign breast epithelium is therefore of interest given the links between estrogen, its receptor, breast epithelial proliferation, and the subsequent non-obligate progression to malignancy. This line of reasoning fits well with the model that non-genotoxic carcinogens can act ...

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“…Recently, Jasper et al (1985) reported different physicochemical forms of ER in rat uterus and pituitary gland based on the hypothesis of a monomer-dimer relationship, and Brown et al (1984) found that the E2 dependent pS2 gene was expressed in the MCF-7 cell line and malignant breast samples but not in normal breast or ER negative cell lines. Similarly, there have been many reports on multiple receptor forms in tissues from animals of different ages and endocrine status (Jasper et al, 1985), on the sedimentation behaviour of molybdate stabilised, non-activated ER, on ER bound to E2 or to antioestrogens and salt or heat-activated receptor (Katzenellenbogen et al, 1978(Katzenellenbogen et al, , 1981McGuire et al, 1978;Grody et al, 1982 andKeen et al, 1984).…”

mentioning

confidence: 99%

“…Similarly, there have been many reports on multiple receptor forms in tissues from animals of different ages and endocrine status (Jasper et al, 1985), on the sedimentation behaviour of molybdate stabilised, non-activated ER, on ER bound to E2 or to antioestrogens and salt or heat-activated receptor (Katzenellenbogen et al, 1978(Katzenellenbogen et al, , 1981McGuire et al, 1978;Grody et al, 1982 andKeen et al, 1984). To date, however, in no organ in any species have differences in binding of a particular steroid metabolite or analogue by ER been reported in a malignant tissue as compared to the normal tissue of the same organ.…”

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confidence: 99%

Differences in oestrogen receptors in malignant and normal breast tissue as identified by the binding of a new synthetic progestogen

Iqbal¹,

Colletta²,

Houmayoun-Valyani³

et al. 1986

Br J Cancer

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Oestrogen receptor protein (ER) was detected in 9 of 11 samples of malignant breast tissue and 8 of 9 samples of normal breast tissue. Levels of cytosolic ER (ERc) in malignant breast were 21-1102 fmol mg-1 soluble protein (Kd 1.8 X 10(-9)-3.1 X 10(-8) mol l-1) and those of nucleosolic ER (ERn), 13-526 fmol mg-1 soluble protein (Kd 2.1 X 10(-9)-1.4 X 10(-8) mol l-1). In normal breast tissue ERc levels were 33-640 fmol mg-1 soluble protein (Kd 1.3 X 10(-10)-3.2 X 10(-9) mol l-1), ERn was detected in only 2 samples, 8 and 87 fmol mg-1 soluble protein with Kd 3.2 X 10(-9) and 1.4 X 10(-9) l mol-1 respectively. 17 alpha-ethinyl-13 beta-ethyl-17 beta-hydroxy-4,15-gonadiene-3-one (gestodene), a new synthetic progestogen displaced 3H-oestradiol (3H-E2) from both ERc and ERn in malignant tissue but not in normal breast, or these receptors from endometrial tissue. In competition studies gestodene was approximately 3 times more effective in displacing 3H-E2 from ERc and ERn in malignant breast tissue than the natural ligand. Quantitation of ER by gestodene were ERc, 12-1134 fmol gestodene bound mg-1 soluble protein (Kd 1 X 10(-9)-8.1 X 10(-9) mol l-1); ERn, 17-531 fmol gestodene bound mg-1 soluble protein (Kd 1.6 X 10(-9)-1.1 X 10(-8) mol l-1). L-13-ethyl-17 alpha-ethinyl, 17 beta-hydroxy-gonen-3-one (levonorgestrel) showed no binding to ER in malignant breast, normal breast or endometrial tissue. In circulation both gestodene and levonorgestrel displaced E2 from sex hormone binding globulin more than any of the androgens tested. These results suggest that gestodene is a progestogen with oestrogenic and/or antioestrogenic properties and provide strong evidence for differences in ER from malignant and normal breast tissue.

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Estrogen and antiestrogen binding to rat uterine and pituitary estrogen receptor: Evidence for at least two physicochemical forms of the estrogen receptor

Cited by 22 publications

References 16 publications

Sex- and Cell-Specific Expression of an Estrogen Receptor Isoform in the Pituitary Gland

Sex- and Cell-Specific Expression of an Estrogen Receptor Isoform in the Pituitary Gland

Estrogen and Progesterone Receptors in Benign Breast Epithelium

Differences in oestrogen receptors in malignant and normal breast tissue as identified by the binding of a new synthetic progestogen

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