Estrogen Regulation of the Biological Activity of the Avian Oviduct Progesterone Receptor and Its Ability to Induce Avidin*

Abstract

During primary estrogen stimulation of chick oviduct development, estrogen withdrawal, or secondary estrogen treatment, changes in the oviduct progesterone receptor (PR) occur. The presence of estrogen appears to regulate not only PR concentration but also its biochemical activity, i.e. its capacity to bind to nuclear acceptor sites and alter RNA synthesis. This study reports that estrogen regulates the nuclear binding capacity of the PR even more rapidly than previously reported in fully developed oviducts of chicks that have been injected daily for 4 weeks with diethylstilbestrol (DES). Further, the nuclear binding capacity of the PR correlates with the ability of progesterone (P) to induce avidin protein concentrations in the oviducts in vivo. The PR concentration in the oviducts increases 2-fold within 8 h of the last injection and the decreases to a minimal value by 24 h. Injection of [3H]P into the chicks shows that the in vivo nuclear localization of the steroid increases almost 4-fold at 8 h, followed by a similar decrease to minimal values by 24 h. Cell-free nuclear binding assays, using PR isolated at various times after the last DES injection and oviduct nucleoprotein complexes, indicate that the capacity of the receptors to bind to nuclear acceptor sites is regulated by the estrogen. The enhanced nuclear binding capacity of the isolated PR increases to maximal values by 12-14 h after the last estrogen treatment and then begins to decrease to minimal values by 24 h. Similarly, the ability of P to induce in vivo avidin protein concentrations and to alter general RNA synthesis in the oviducts is reduced by 70% (of the estrogen non-withdrawn chick levels) by 24 h after the last estrogen injection. These changes over the 24-h period after the last DES treatment are not due to changes in the serum DES concentrations. The following 10-day period of estrogen withdrawal reveals a cyclic decaying pattern in the capacity of the PR for nuclear binding. The P induction of avidin and alteration of RNA polymerase II activity, using nuclear run-off experiments, also show a similar cyclic decaying pattern. By 6 days of estrogen withdrawal, the PR is incapable of any nuclear binding, and P cannot induce avidin protein concentrations in the oviducts. Serum DES concentrations over this 10-day period display only a gradual decay.(ABSTRACT TRUNCATED AT 400 WORDS)

Rat Uterine Progesterone Receptor Analyzed by [3H]R5020 Photoaffinity Labeling: Evidence that the A and B Subunits Are Not Equimolar*

“…Among the alternative explanations for the high A/B ratio observed herein is selection for these studies of rats in a physiological state with an altered ratio (21)(22)(23)(24). The high A/B ratio was observed essentially throughout the year, ruling out seasonal variation as a contributing factor herein.…”

“…However, there is now controversy as to whether they represent truly independent receptor forms or whether the smaller A component is a proteolytic product of B (18)(19)(20). In addition to the in vitro evidence suggesting the importance of both A and B for regulation of gene transcription by the receptor (1, 3), Spelsberg and associates (21) have presented several lines of evidence resulting in the interpretation that alterations in the A/B subunit ratio may be detrimental to receptor function (21)(22)(23)(24). In addition to the in vitro evidence suggesting the importance of both A and B for regulation of gene transcription by the receptor (1, 3), Spelsberg and associates (21) have presented several lines of evidence resulting in the interpretation that alterations in the A/B subunit ratio may be detrimental to receptor function (21)(22)(23)(24).…”

“…As a consequence, the question of whether both components participate in mediating progestational effects and the additional question of the significance of the subunit ratio are unresolved. Their studies indicated both a seasonal variation (22) and an estrogen dependence (23,24) in the relative levels of the two subunits in the chick oviduct progesterone receptor. Their studies indicated both a seasonal variation (22) and an estrogen dependence (23,24) in the relative levels of the two subunits in the chick oviduct progesterone receptor.…”

Nuclease resistance and the enrichment of native nuclear acceptor sites for the avian oviduct progesterone receptor.

“…In contrast to the receptor binding to pure DNA sequences alone (5,6), the binding of the oviduct PR to subfractions of chromatin containing nonhistone protein-DNA complexes, termed nucleoacidic protein or NAP, has been shown to be receptor dependent and saturable, of high affinity (7)(8)(9)(10)(11), to be receptor specific (12), and to generate patterns of bindings similar to that measured in vivo (13)(14)(15)(16). Further, the capacity of the PR to bind to nuclear acceptor sites reflects the ability of progesterone to alter RNA polymerase activity in nuclear run-off experiments (17, t) and to specifically induce the avidin gene (18). A specific subset of nonhistone proteins (acceptor proteins) has been shown to be necessary for the generation of specific nucleoprotein acceptor sites (10,11,(19)(20)(21).…”

Changes in steroid receptor activation, cell kinetics and tumor growth rate, during progression of human endometrial adenocarcinomas growing in nude mice: a brief review

“…One possible explanation for this is that estradiol results in conformafional alterations in a part of the induced non-activated PgR so that its low affinity binding is enhanced. Another possibility is that estradiol treatment alters chromatin protein composition, and that such changes in the acceptor sites may explain variations in the ability of PgR to bind to chromatin (22)(23)(24).…”