Comparison of Effects of Estetrol and Tamoxifen with Those of Estriol and Estradiol on the Immature Rat Uterus1

Holinka, Christian F.; Bressler, Robert S.; Zehr, David R.; Gurpide, Erlio

doi:10.1095/biolreprod22.4.913

Cited by 46 publications

(21 citation statements)

References 21 publications

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“…In contrast, tamoxifen has clear-cut estrogenic actions in the rat. There is a partial increase in uterine wet weight (24), a full stimulation of uterine luminal epithelial cells (39,40), progesterone receptor synthesis (41,42), and ornithine decarboxylase activity (43). Circulating levels of renin substrate are increased equally by estradiol and tamoxifen (44,45), and prolonged treatment with tamoxifen completely lowers the circulating level of luteinizing hormone (LH) in the ovariectomized rat (46).…”

Section: Pharmacology Of Tamoxifenmentioning

confidence: 99%

Metabolites of tamoxifen in animals and man: Identification, pharmacology, and significance

Jordan

Chem

1982

Breast Cancer Res Tr

128

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Over the past decade, the non-steroidal antiestrogen tamoxifen has gained general acceptance for the palliative treatment of breast cancer. Although there has been much interest in the pharmacology of tamoxifen, our knowledge of its metabolism in laboratory animals and patients is incomplete and the precise mechanism of action within target tissue and breast tumor cells is unknown. This review briefly describes the pharmacology of tamoxifen in various laboratory species and patients. Several metabolites of tamoxifen are known and their relative potencies as estrogens and antiestrogens are compared with the parent compound. Apart from monohydroxytamoxifen, none of tamoxifen's metabolites are more potent antiestrogens, but a metabolite in the dog, Metabolite E, is fully estrogenic. Routine assays (tlc, HPLC, glc/ms) are available to detect tamoxifen, N-desmethyltamoxifen, monohydroxytamoxifen, and a newly identified metabolite, designated Metabolite Y, in biological fluids. Continuous therapy with tamoxifen (10 mg bid) produces steady-state levels (100-200 ng/ml serum) within 4 weeks. Levels of N-desmethyltamoxifen are often up to twice the levels achieved with tamoxifen, while levels of monohydroxytamoxifen and Metabolite Y are below 10 ng/ml. Although monohydroxytamoxifen has a high binding affinity for the estrogen receptor, the metabolic activation of tamoxifen is an advantage rather than a requirement for antiestrogenic activity. The action of tamoxifen in vivo is the net result of the individual actions of the parent compound and its metabolites competing for the occupation of receptors within target tissues and tumors.

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Section: Pharmacology Of Tamoxifenmentioning

confidence: 99%

Metabolites of tamoxifen in animals and man: Identification, pharmacology, and significance

Jordan

Chem

1982

Breast Cancer Res Tr

128

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“…Autolytic bodies have effectively been observed in uterus of rats receiving injections of estrogens [Holinka et al, 1980;,…”

Section: Discussionmentioning

confidence: 99%

The Hedgehog Uterus

Lescoat

Saboureau

Castaing

et al. 1985

Cells Tissues Organs

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The ultrastructure of the luminal epithelium of the hedgehog uterus is described on the basis of material taken from 11 animals in three different hormonal situations: castrated, active and hibernating animals. The whole uterine epithelium is composed of microvillous cells. Its appearance is very similar in ovariectomized and hibernating animals. It differs from that observed in active animals where the epithelium is taller, microvilli are more numerous and longer, and where nuclei and cytoplasm display a very active ultrastructural appearance. The results now available indicate that ultrastructural changes occurring within the cells are certainly correlated with plasma sex steroid hormone concentrations. The present paper also reports the regular occurrence of nuclear bodies in uterine cells.

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“…The uterine effects of E 4 were further characterized by evaluating changes in progesterone receptors and histologic and ultrastructural features of the immature rat uterus in response to E 4 [43]. Tamoxifen (TAM) was included in these studies as an additional comparator.…”

Section: Rodent Uterusmentioning

confidence: 99%

“…Necrotic cells were seen both in E4 and E2 (arrow) tissues. (Reproduced with permission from Holinka et al [43]). electron microscopy.…”

Section: Rodent Uterusmentioning

confidence: 99%

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Estetrol: A unique steroid in human pregnancy

Holinka¹,

Diczfalusy

Bennink

2008

The Journal of Steroid Biochemistry and Molecular Biology

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Comparison of Effects of Estetrol and Tamoxifen with Those of Estriol and Estradiol on the Immature Rat Uterus1

Abstract: The estrogenic effects on this immature rat uterus of estetrol 11,3 ,5( 10)-estratriene-3

Cited by 46 publications

References 21 publications

Metabolites of tamoxifen in animals and man: Identification, pharmacology, and significance

Metabolites of tamoxifen in animals and man: Identification, pharmacology, and significance

The Hedgehog Uterus

Estetrol: A unique steroid in human pregnancy

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