Comparative effects of 28-day treatment with the new anti-estrogen EM-800 and tamoxifen on estrogen-sensitive parameters in intact mice

Luo, Shouqi; Martel, Céline; Sourla, Antigone; Gauthier, Sylvie F.; Mérand, Yves; Bélanger, Alain; Labrie, Claude; Labrie, Fernand

doi:10.1002/(sici)1097-0215(19971104)73:3<381::aid-ijc13>3.0.co;2-g

Cited by 50 publications

(24 citation statements)

References 23 publications

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“…However, RU 58668 does disrupt nuclear localisation (Devin-Leclerc et al 1998) and, like ICI 182780, leads to rapid loss of ER in human breast cancer cell lines (Müller et al 1998). No similar studies have been reported for the nonsteroidal pure antioestrogens but analysis of oestrogen binding capacity of the uterus after long-term treatment of rats or mice with EM-800 indicated loss of ER (Luo et al 1997. This loss of ER may be a consequence of tissue atrophy rather than the acute 'downregulation' of ER observed following treatment with the steroidal pure antioestrogens.…”

Section: Figurementioning

confidence: 85%

“…RU 58668, Nique et al 1994). Further synthetic chemistry at Zeneca and elsewhere produced non-steroidal molecules completely free of agonist activity; for example ZM 189154, in which the alkysulphinyl side-chain of ICI 182780 is substituted on a 2-methyl tetrahydronaphthalene (Dukes et al 1994), EM-800, a benzopyran derivative (Gauthier et al 1997), and dichlorotriarylcyclopropanes (Day et al 1991).…”

Section: Introductionmentioning

confidence: 99%

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Similarities and distinctions in the mode of action of different classes of antioestrogens.

Wakeling

2000

Endocrine-Related Cancer

176

100

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Section: Figurementioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Similarities and distinctions in the mode of action of different classes of antioestrogens.

Wakeling

2000

Endocrine-Related Cancer

176

100

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“…Indeed, withdrawal of estradiol via ovariectomy (West et al 1978) or administration of antiestrogen agents (Luo et al 1997) results in uterine atrophy. Interestingly, the first significant decline in uterine mass in the present study occurred at 3 weeks of SD exposure, when diestrus II estradiol concentrations were still elevated and comparable to those of LD hamsters.…”

Section: Discussionmentioning

confidence: 99%

Short photoperiod-induced ovarian regression is mediated by apoptosis in Siberian hamsters (Phodopus sungorus)

Moffatt-Blue

Sury²,

Young³

2006

Reproduction

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Siberian hamster reproduction is mediated by photoperiod-induced changes in gonadal activity. However, little is known about how photoperiod induces cellular changes in ovarian function. We hypothesized that exposing female hamsters to short (inhibitory) as opposed to long (control) photoperiods would induce an apoptosis-mediated disruption of ovarian function. Ovaries and plasma from hamsters exposed to either long (LD, 16 h light:8 h darkness) or short (SD, 8 h light:16 h darkness) days were collected during diestrus II after 3, 6, 9 and 12 weeks and processed for histology or RIA respectively. Apoptosis was assessed by in situ TUNEL and active caspase-3 protein immunolabeling. No significant differences were observed among LD hamsters for any parameter; therefore, these control data were pooled. SD exposure induced a decline in preantral follicles (P < 0.05), early antral/antral follicles (P < 0.01) and corpora lutea (P < 0.01) by week 12 as compared with LD. Terminal atretic follicles appeared by SD week 9; by week 12, these had become the predominant ovarian structures. Estradiol concentrations decreased by weeks 9 and 12 SD when compared with both LD and week-3 SD hamsters (P < 0.05); however, no changes were observed for progesterone. TUNEL-positive follicles in SD ovaries increased at week 3 and subsequently declined by week 12 as compared with LD ovaries (P < 0.01). Active capsase-3 protein immunostaining peaked at SD week 3 as compared with all other groups (P < 0.01). TUNEL and capsase-3 immunolabeling were localized to granulosa cells of late-preantral and early-antral/antral follicles. These data indicate that SD exposure rapidly induces follicular apoptosis in Siberian hamsters, which ultimately disrupts both estradiol secretion and folliculogenesis, resulting in the seasonal loss of ovarian function. IntroductionTo maximize survival when environmental resources are reduced, individuals of many temperate species limit reproductive function seasonally. In mammals, this adaptation is cued primarily by photoperiod-induced alterations in melatonin secretion from the pineal gland. For long-day (LD) seasonal breeders, such as Siberian hamsters (Phodopus sungorus), exposure to long photoperiods (. 12.5 h of light per day; short duration of melatonin release) induces and maintains reproductive function, whereas exposure to short photoperiods (, 12.5 h of light per day; long duration of melatonin release) results in the cessation of reproductive function (Hoffmann 1986, Bronson 1989, Knopper & Boily 2000, Prendergast & Nelson 2001. Extended periods of melatonin secretion negatively affect reproductive activity via inhibition of the hypothalamic-pituitary-gonadal (HPG) axis. In both males and females, short-day (SD) exposure reduces hypothalamic synthesis and secretion of gonadotropin-releasing hormone (GnRH) and, subsequently, the pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (Glass 1986, Buchanan & Yellon 1991. Eventually, these endocrine alterations resu...

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“…An effect on the vaginal mucosa similar to that observed in ERα-null females is produced in rodents after prolonged ovariectomy or exposure to ER antagonists. [217][218][219] Therefore, estrogenization of the vaginal mucosa in rodents, which is critical to mating, is ERα dependent. Using a human papilloma virus (HPV) transgenic model of cervical cancer, Chung et al demonstrated that estrogen promotes development of HPV-induced cervical cancer through ERα, as αERKO HPV-transgenic animals were protected from developing disease.…”

Section: Vaginal and Cervical Phenotypes In Mouse Models Of Disruptedmentioning

confidence: 99%

“…Indeed, prolonged treatment of female rodents with antiestrogens that cross the blood-brain barrier (e.g., ZM-189,154, EM-800) and produce an αERKO-like gonadotropin profile lead to a similar ovarian phenotype; whereas treatments with tamoxifen, a receptor antagonist that does not alter gonadotropin secretion generates no such effects in the ovary. [217][218][219] A prominent phenotype in αERKO ovaries that may be indicative of an intraovarian role for ERα is their elevated capacity to synthesize androgens. 431 Relative to their wild-type littermates, αERKO females possess plasma levels of androstenedione and T that are increased 3 and 40-fold, respectively.…”

Section: Figure 2517 Ovarian Phenotypes In Er-null Mice (A-c) Shownmentioning

confidence: 99%

Steroid Receptors in the Uterus and Ovary

Binder

Winuthayanon

Hewitt

et al. 2015

Knobil and Neill's Physiology of Reproduction

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Comparative effects of 28-day treatment with the new anti-estrogen EM-800 and tamoxifen on estrogen-sensitive parameters in intact mice

Cited by 50 publications

References 23 publications

Similarities and distinctions in the mode of action of different classes of antioestrogens.

Similarities and distinctions in the mode of action of different classes of antioestrogens.

Short photoperiod-induced ovarian regression is mediated by apoptosis in Siberian hamsters (Phodopus sungorus)

Steroid Receptors in the Uterus and Ovary

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