A congenic strain of rat for investigation of control of estrogen-induced growth

Wendell, Douglas L.; Pandey, Sudhir Kumar; Kelley, Parker

doi:10.1007/s00335-002-2183-6

Cited by 9 publications

(5 citation statements)

References 9 publications

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“…In animal models, these tumours usually regress upon withdrawal of administered hormones. But, after long-term treatment with oestrogens, these tumours can progress to a hormoneindependent state, associated with changes in their histological features, culminating in neoplastic transformation (Spady et al, 1999;Wendell et al, 2002). The stimulus of pituitary DNA synthesis and pituitary growth by oestrogens varies with the rat strains suggesting that the excessive proliferative response of the lactotrophs might be genetically determined (Spady et al, 1999;Strecker et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy

et al. 2014

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Male-to-female transsexual persons use oestrogens + antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self-administration of cross-sex hormones, doses may be very high. Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male-to-female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events. We report two new cases of prolactinomas in male-to-female transsexual persons, one in a 41-year-old subject who had used nonsupervised high-dose oestrogen treatment since the age of 23 years and another one in a 42 year old who had initiated oestrogen treatment at the age of 17 years. Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised. Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens.

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Section: Discussionmentioning

confidence: 99%

Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy

et al. 2014

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“…Each of the QTL mapped in these studies of estrogen action on the pituitary lactotroph resides in a distinct region of the rat genome, although the mapping resolution for Edpm3 and Ept2 , both of which reside on rat chromosome 3, is insufficient to demonstrate conclusively that these two QTL are distinct entities. Several of these QTL that harbor genetic determinants of responsiveness of the rat pituitary gland to estrogens have been isolated as congenic rat strains, which will allow the genetic variants that impact responsiveness to estrogens to be mapped to higher resolution and their molecular actions to be further elucidated (Dennison et al 2015; Kurz et al 2014; Kurz et al 2008; Pandey et al 2004; Wendell et al 2002). The presence of multiple loci regulating responses to estrogens and that these are distinct for mammary gland and uterus highlights the tissue-specific nature of estrogen signaling and its complexity.…”

Section: Genetic Variants Determining Responses To Estrogenmentioning

confidence: 99%

Genetic variation in sensitivity to estrogens and breast cancer risk

et al. 2018

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Breast cancer risk is intimately intertwined with exposure to estrogens. While more than 160 breast cancer risk loci have been identified in humans, genetic interactions with estrogen exposure remain to be established. Strains of rodents exhibit striking differences in their responses to endogenous ovarian estrogens (primarily 17β-estradiol). Similar genetic variation has been observed for synthetic estrogen agonists (ethinyl estradiol) and environmental chemicals that mimic the actions of estrogens (xenoestrogens). This review of literature highlights the extent of variation in responses to estrogens among strains of rodents and compiles the genetic loci underlying pathogenic effects of excessive estrogen signaling. Genetic linkage studies have identified a total of the 35 quantitative trait loci (QTL) affecting responses to 17β-estradiol or diethylstilbestrol in 5 different tissues. However, the QTL appear to act in a tissue-specific manner with 9 QTL affecting the incidence or latency of mammary tumors induced by 17β-estradiol or diethylstilbestrol. Mammary gland development during puberty is also exquisitely sensitive to the actions of endogenous estrogens. Analysis of mammary ductal growth and branching in 43 strains of inbred mice identified 20 QTL. Regions in the human genome orthologous to the mammary development QTL harbor loci associated with breast cancer risk or mammographic density. The data demonstrate extensive genetic variation in regulation of estrogen signaling in rodent mammary tissues that alters susceptibility to tumors. Genetic variants in these pathways may identify a subset of women who are especially sensitive to either endogenous estrogens or environmental xenoestrogens and render them at increased risk of breast cancer.

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“…The Fischer 344 (F344) rat has long been used as a model for investigating growth control of estrogen-responsive tissues (especially those prone to estrogen-induced tumors), by various estrogens, and related biological processes such as angiogenesis [3,4]. When female F344 rats are chronically treated with E 2 or the pharmaceutical estrogen diethylstilbestrol (DES), their pituitaries grow 10 to 20 times normal size and sometimes form a tumor by 10 weeks [5,6].…”

Section: Introductionmentioning

confidence: 99%

Subchronic exposure to phytoestrogens alone and in combination with diethylstilbestrol - pituitary tumor induction in Fischer 344 rats

et al. 2010

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Background: Subchronic administration of the potent pharmaceutical estrogen diethylstilbestrol (DES) to female Fischer 344 (F344) rats induces growth of large, hemorrhagic pituitaries that progress to tumors. Phytoestrogens (dietary plant estrogens) are hypothesized to be potential tumor inhibitors in tissues prone to estrogen-induced cancers, and have been suggested as "safer" estrogen replacements. However, it is unknown if they might themselves establish or exacerbate the growth of estrogen-responsive cancers, such as in pituitary. Methods:We implanted rats with silastic capsules containing 5 mg of four different phytoestrogens -either coumestrol, daidzein, genistein, or trans-resveratrol, in the presence or absence of DES. We examined pituitary and other organ weights, blood levels of prolactin (PRL) and growth hormone (GH), body weights, and pituitary tissue histology.Results: Blood level measurements of the administered phytoestrogens confirmed successful exposure of the animals to high levels of these compounds. By themselves, no phytoestrogen increased pituitary weights or serum PRL levels after 10 weeks of treatment. DES, genistein, and resveratrol increased GH levels during this time. Phytoestrogens neither changed any wet organ weight (uterus, ovary, cervix, liver, and kidney) after 10 weeks of treatment, nor reversed the adverse effects of DES on pituitaries, GH and PRL levels, or body weight gain after 8 weeks of co-treatment. However, they did reverse the DES-induced weight increase on the ovary and cervix. Morphometric examination of pituitaries revealed that treatment with DES, either alone or in combination with phytoestrogens, caused gross structural changes that included decreases in tissue cell density, increases in vascularity, and multiple hemorrhagic areas. DES, especially in combination with phytoestrogens, caused the development of larger and more heterogeneous nuclear sizes in pituitary.Conclusions: High levels of phytoestrogens by themselves did not cause pituitary precancerous growth or change weights of other estrogen-sensitive organs, though when combined with DES, they counteracted the growth effects of DES on reproductive organs. In the pituitary, phytoestrogens did not reverse the effects of DES, but they did increase the sizes and size heterogeneity of nuclei. Therefore, phytoestrogens may oppose some but not all estrogenresponsive tissue abnormalities caused by DES overstimulation, and appear to exacerbate DES-induced nuclear changes. BackgroundSteroid hormones such as the dominant physiologic estrogen, estradiol (E 2 ) have many effects on pituitary function, including regulation of most pituitary hormones and proliferation of several pituitary cell types

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A congenic strain of rat for investigation of control of estrogen-induced growth

Cited by 9 publications

References 9 publications

Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy

Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy

Genetic variation in sensitivity to estrogens and breast cancer risk

Subchronic exposure to phytoestrogens alone and in combination with diethylstilbestrol - pituitary tumor induction in Fischer 344 rats

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