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Competitive progesterone antagonists: receptor binding and biologic activity of testosterone and 19-nortestosterone derivatives.

Abstract：

:Testosterone and 19-nortestosterone derivatives were evaluated in a developmental scheme designed to identify competitive progesterone antagonists having abortifacient activity. Compounds that displayed significant binding to the rabbit uterine progesterone receptor were followed in biologic tests for progestational, antiprogestational, and abortifacient activities. Of the seven compounds tested for both progestational and antiprogestational activity, only one, 5 alpha-dihydronorethindrone, behaved exclusively as an antagonist. Five other 19-nortestosterones (19-nortestosterone, 17 beta-hydroxyestra-4, 9(10)-dien-3-one, norethindrone, norethindrone acetate, and R 2323) proved to be mixed agonists/antagonists. 5 alpha-Dihydronorethindrone, norethindrone, and 19-nortestosterone terminated pregnancy during the postnidatory period in rats; in addition, the latter two compounds inhibited progesterone-supported pregnancy in spayed rats and curtailed pregnancy during the postnidatory period in hamsters. These results demonstrate that several 19-nortestosterone derivatives bind to the uterine progesterone receptor and behave either as antagonists or mixed agonists/antagonists.

journal_name

Fertil Steril

journal_title

Fertility and sterility

authors

Reel JR,Humphrey RR,Shih YH,Windsor BL,Sakowski R,Creger PL,Edgren RA

doi

10.1016/s0015-0282(16)44003-3

subject

Has Abstract

pub_date

1979-05-01 00:00:00

pages

552-61

issue

5

eissn

0015-0282

issn

1556-5653

pii

S0015-0282(16)44003-3

journal_volume

31

pub_type

杂志文章

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