Estrogen and antiestrogen action: studies in reproductive target tissues and tumors.

Benita S Katzenellenbogen, T. S. Tsai, T. Tatee, J. A. Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

Studies are reported using unlabelled and radiolabelled antiestrogens which are aimed at elucidating the nature of interaction of antiestrogens with uterine and mammary tissue. Antiestrogens and long-acting estrogens move estrogen receptor sites to the nucleus and maintain elevated nuclear receptor levels for a prolonged period. The antagonistic action of antiestrogens in the uterus, however, appears to derive from their ability to effect a marked perturbation in the subcellular distribution of receptor whereby very little (ca. 10%) is cytoplasmic and further estrogen receptor accumulation is blocked. In DMBA-induced rat mammary tumors, the nonphototoxic antiestrogen, U-23, 469, effectively antagonizes the development and growth of tumors and elicits regression of 90% of established tumors with a time course similar to that seen after ovariectomy. Again, during antiestrogen treatment, the levels of cytoplasmic estrogen receptor are depressed with over 90% of total receptor being found in the nucleus. Two radiolabelled antiestrogens of high specific activity and purity have been prepared by us and their interaction with nuclear and cytoplasmic estrogen receptors is reported. Both 3H-CI-628 and 3H-U-23, 469 are metabolized in vivo to more polar forms which are found associated with the nuclear estrogen receptor, and which may be the true agents active in vivo.

Original languageEnglish (US)
Pages (from-to)111-132
Number of pages22
JournalAdvances in experimental medicine and biology
Volume117
StatePublished - Jan 1 1979
Externally publishedYes

Fingerprint

Estrogen Receptor Modulators
Tumors
Estrogens
Tissue
Estrogen Receptors
Cytoplasmic and Nuclear Receptors
Neoplasms
Nitromifene
9,10-Dimethyl-1,2-benzanthracene
Ovariectomy
Growth and Development
Uterus
Rats
Breast
Breast Neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Estrogen and antiestrogen action : studies in reproductive target tissues and tumors. / Katzenellenbogen, Benita S; Tsai, T. S.; Tatee, T.; Katzenellenbogen, J. A.

In: Advances in experimental medicine and biology, Vol. 117, 01.01.1979, p. 111-132.

Research output: Contribution to journalArticle

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