Effects of tamoxifen and ethynylestradiol cotreatment on uterine gene expression in immature, ovariectomized mice

Fong, C. J.; Burgoon, Lyle D.; Williams, Kurt J.; Jones, A. Daniel; Forgacs, Agnes L.; Zacharewski, Timothy R.

doi:10.1677/jme-09-0158

Cited by 10 publications

(8 citation statements)

References 70 publications

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“…The mean uterine relative weight was approximately 60% of EE2 control value and histopathological examination confirmed attenuated proliferative effect. Our results are largely consistent with the literature data obtained using immature rats, in which case significant uterotrophic effects of EE2 were observed at doses from 0.3 to 3 µg/kg b.w./d (9,12,13,14,16,24,28) and antagonistic effects of tamoxifen at the dose of 1 mg/kg b.w/d (7).…”

Section: Discussionsupporting

confidence: 92%

Usefulness of immature golden hamster (Mesocricetus auratus) as a model for uterotrophic assay

Radko

Minta

Jasik

et al. 2015

Bulletin of the Veterinary Institute in Pulawy

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The present study assessed the sensitivity of immature hamster uterotrophic assay to reference oestrogen agonists/antagonists in order to develop a sensitive model for evaluation of endocrine-active compounds in diets. After performing a baseline for control animals, the sensitivity of immature females (postnatal day 18) to reference compounds was evaluated in a three-day uterotrophic assay. The absolute and adjusted dry uterine weights, fold induction over control for absolute wet uterine weight, and wet uterine weight/body weight ratio (%) were used as endpoints. The significantly active doses for reference oestrogens were as follows: 0.6 µg/kg for 17α-ethinyloestradiol (s.c.); 1 µg/kg/day (s.c.) and 40 µg/kg (p.o.) for diethylstilboestrol; 40 mg/kg (s.c.) and 160 mg/kg (p.o.) for bisphenol A. Co-treatment with tamoxifen at a dose of 1 mg/kg significantly antagonised the uterotrophic effect induced by 1 µg/kg 17α-ethinyloestradiol, and showed the attenuated proliferative effect in histopathological examination. We found immature hamster uterotrophic assay as a sensitive model that could be a good alternative to the rat assay.

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Section: Discussionsupporting

confidence: 92%

Usefulness of immature golden hamster (Mesocricetus auratus) as a model for uterotrophic assay

Radko

Minta

Jasik

et al. 2015

Bulletin of the Veterinary Institute in Pulawy

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“…In accordance with the previous literature [35,36,37], this dose generated a uterotrophic response, reflected by the increase in uterine wet weight at sacrifice. G-1 injections, on the other hand, did not increase uterine wet weight; this is in agreement with a previous study in which a range of G-1 doses, from 0.5 to 100 μg/mouse, did not stimulate uterine weight gain [38].…”

Section: Discussionsupporting

confidence: 90%

Activation of the GPR30 Receptor Promotes Lordosis in Female Mice

Anchan

Gafur²,

Sato³

et al. 2014

Neuroendocrinology

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Background/Aims: Estrogens are important effectors of reproduction and are critical for upregulating female reproductive behavior or lordosis in females. In addition to the importance of transcriptional regulation of genes by 17β-estradiol-bound estrogen receptors (ER), extranuclear signal transduction cascades such as protein kinase A (PKA) are also important in regulating female sexual receptivity. GPR30 (G-protein coupled receptor 30), also known as GPER1, a putative membrane ER (mER), is a G protein-coupled receptor that binds 17β-estradiol with an affinity that is similar to that possessed by the classical nuclear ER and activates both PKA and extracellular-regulated kinase signaling pathways. The high expression of GPR30 in the ventromedial hypothalamus, a region important for lordosis behavior as well as kinase cascades activated by this receptor, led us to hypothesize that GPR30 may regulate lordosis behavior in female rodents. Method: In this study, we investigated the ability of G-1, a selective agonist of GPR30, to regulate lordosis in the female mouse by administering this agent prior to progesterone in an estradiol-progesterone priming paradigm prior to testing with stud males. Results: As expected, 17β-estradiol benzoate (EB), but not sesame oil, increased lordosis behavior in female mice. G-1 also increased lordosis behavior in female mice and decreased the number of rejective responses towards male mice, similar to the effect of EB. The selective GPR30 antagonist G-15 blocked these effects. Conclusion: This study demonstrates that activation of the mER GPR30 stimulates social behavior in a rodent model in a manner similar to EB.

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“…Tamoxifen, a first generation SERM, provided the desired protective effect in the breast [31,32] and raloxifene, a second generation SERM, had protective properties in breast and bone tissues [26,27,103]. However, as these SERMS have been linked to the increased occurrence of hot flashes and stimulated endometrial growth (tamoxifen), the search continues [28,34,35]. Third generation SERMs, such as lasoxifene and bazedoxifene, are currently in development, but the focus has shifted to osteoporosis treatment with protection against breast cancer as a beneficial side effect [104-106].…”

Section: Discussionmentioning

confidence: 99%

Cyclopia Extracts Act as ERα Antagonists and ERβ Agonists, In Vitro and In Vivo

2013

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Hormone replacement therapy associated risks, and the concomitant reluctance of usage, has instigated the search for new generations of estrogen analogues that would maintain estrogen benefits without associated risks. Furthermore, if these analogues display chemo-preventative properties in breast and endometrial tissues it would be of great value. Both the selective estrogen receptor modulators as well as the selective estrogen receptor subtype modulators have been proposed as estrogen analogues with improved risk profiles. Phytoestrogen containing extracts of Cyclopia, an indigenous South African fynbos plant used to prepare Honeybush tea may serve as a source of new estrogen analogues. In this study three extracts, P104, SM6Met, and cup-of-tea, from two species of Cyclopia, C. genistoides and C. subternata, were evaluated for ER subtype specific agonism and antagonism both in transactivation and transrepression. For transactivation, the Cyclopia extracts displayed ERα antagonism and ERβ agonism when ER subtypes were expressed separately, however, when co-expressed only agonism was uniformly observed. In contrast, for transrepression, this uniform behavior was lost, with some extracts (P104) displaying uniform agonism, while others (SM6Met) displayed antagonism when subtypes were expressed separately and agonism when co-expressed. In addition, breast cancer cell proliferation assays indicate that extracts antagonize cell proliferation in the presence of estrogen at lower concentrations than that required for proliferation. Furthermore, lack of uterine growth and delayed vaginal opening in an immature rat uterotrophic model validates the ERα antagonism of extracts observed in vitro and supports the potential of the Cyclopia extracts as a source of estrogen analogues with a reduced risk profile.

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Effects of tamoxifen and ethynylestradiol cotreatment on uterine gene expression in immature, ovariectomized mice

Cited by 10 publications

References 70 publications

Usefulness of immature golden hamster (Mesocricetus auratus) as a model for uterotrophic assay

Usefulness of immature golden hamster (Mesocricetus auratus) as a model for uterotrophic assay

Activation of the GPR30 Receptor Promotes Lordosis in Female Mice

Cyclopia Extracts Act as ERα Antagonists and ERβ Agonists, In Vitro and In Vivo

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