New Look at the Very Early Steps of Oestrogen Action in Uterus

Baulieu, Étienne Émile; Alberga, Audrey; Raynaud-Jammet, C.; Wira, Charles R.

doi:10.1038/newbio236236a0

Cited by 70 publications

(13 citation statements)

References 27 publications

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“…On the other hand, another pos sibility is that, initially, during the lag period, there is only synthesis of one or a very limited number of key intermediary protein(s) (KIP), respon sible secondarily for the generalized protein synthesis. In the latter case, the activation of only a limited number of genes would be sufficient, and the rare estradiol-binding NHC could be 'logically' involved [4]. One interest of the last concept, among others, is that such a limited inter mediary KIP product could still be a potential target for a specific anti hormone effect.…”

Section: First Effects Of Estradiolmentioning

confidence: 99%

Estrogens and Antiestrogens

Geynet¹,

Millet²,

Truong³

et al. 1972

Gynecol Obstet Invest

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This paper contains: A review of the features implicated in estrogen action on uterine cells: metabolism, transport, entry, cytosol receptor, and first effects. (2) New results concerning the interaction of several estrogens and antiestrogens with the receptor. Binding of radioactive estrogens: at equilibrium at 0 °C, K_D (in nM) of estradiol 0.2–0.5, estrone 2.0, and estriol 1.3. Inhibition constant at equilibrium measured by competition with nonradioactive compounds of natural and synthetic steroid and nonsteroidal estrogens, new stilbene derivatives, phytoestrogens, etc. (28 compounds). Kinetic studies. Same dissociation rate constant for estradiol, estrone and estriol and association rate constant greater for estradiol. Formation of the neonuclear steroid receptor complex by estrone and estriol, implicating that estradiol is not unique for promoting the cytosol receptor translocation to the nucleus. (3) A review of possible mechanisms for antiestrogen action.

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Section: First Effects Of Estradiolmentioning

confidence: 99%

Estrogens and Antiestrogens

Geynet¹,

Millet²,

Truong³

et al. 1972

Gynecol Obstet Invest

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“…In order to see whether the results of Vokaer et al (8) were due to the presence of additional species of PPPase which may be associated with IP in adult but not immature rat uteri, we repeated the above electrophoretic separation using cytosol from a proestrous rat (which has the highest endogenous level of IP synthesis [18,19] …”

Section: Resultsmentioning

confidence: 99%

“…Because the appearance of IP represents one of the earliest effects of estradiol on the uterus, Baulieu et al (8) have proposed that IP is the "key intermediate protein" in the stimulation of bulk RNA synthesis by estradiol. However, until a recent report by Vokaer et al (9), no experimental data on the possible function of IP were available.…”

mentioning

confidence: 99%

Separation of "estrogen-induced" protein from phosphoprotein phosphatase activity of immature rat uterus.

Kaye¹,

Walker²,

Sömjen³

1975

Proc. Natl. Acad. Sci. U.S.A.

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Preparations of the "induced protein" which appears in the rat uterus within 40 min of estradiol administration have recently been reported to contain phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) activity. We found that these two proteins distribute differently on ammonium sulfate fractionation of uterine cytosol. Preparative cellulose acetate electrophoresis afforded complete (>99.9%) separation of phosphoprotein phosphatase activity from the induced protein. The specific activity of phosphoprotein phosphatase in uterine cytosol was unchanged 1, 4, 12, or 24 hr after estradiol administration. These results are incompatible with the view that the induced protein mediates estrogen action by virtue of an inherent phosphoprotein phosphatase activity. Administration of estradiol-17fl to immature rats, or mature ovariectomized rats, results in an increased rate of synthesis of a uterine protein which has been designated "induced protein" (IP) by Notides and Gorski (1). Synthesis of estrogen-induced protein can be detected within 40 min of estradiol injection into rats (2) The proposal of Liu and Greengard (10), that increases in PPPase activity may modulate the response of toad bladder to the steroid hormone aldosterone, lends plausibility to the idea that an increase in PPPase activity may also be involved in the mechanism of estrogen action. In view of the conceptual importance of the identification of the function of IP and the practical advantage of having an enzymic activity for the quantitation of IP in our uterine cell-free synthetic system (11), we investigated the relationship between IP and PPPase. We studied the distribution of IP and PPPase during fractionation by ammonium sulfate precipitation and electrophoresis on cellulose acetate gels and found it possible to separate IP and PPPase activity.

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“…In this work a discrete early increase of incorporation of radioactive leucine into proteins may be related to the very early increase of many RNA species after injection of hormone [39] (and M. G. Catelli, unpublished results) and to the receptor-estradiol dependent increase of RNA polymerases A and B activities in isolated nuclei [40]. It remains to be seen whether such a non-selective increase is associated with some rate-limiting step necessary to set up the complete secondary response of the uterus to estradiol (cascade mechanism), or if there is no intermediary step (one-step mechanism) but a progressive quantitative development of the response starting from the very beginning as a coordinated complex event [15]. However, it is found here that the increase is rather slow until 4 h, whereas there is an accelerated augmentation after 6 h (unpublished results).…”

Section: Discussionmentioning

confidence: 99%

Steroid‐Induced Early Protein Synthesis in Rat Uterus and Prostate

Pennequin

Röbel

Baulieu

1975

European Journal of Biochemistry

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An early ‘induced protein’, after exposure of the rat uterus to estradiol, is detected among the soluble proteins with a double‐labelling technique and electrophoretic fractionation. Efforts have been directed to establish the subcellular distribution of the induced protein, since such a protein, observable 1 h after hormone administration, may play an important role in the subsequent amplified responses, especially in terms of RNA synthesis. Moreover such an early discrete induced protein was sought in a comparable system responding to another hormone, namely prostate and seminal vesicles under androgens. The induced protein was not found in uterine nuclei of 21‐day‐old rats after 1 h of estradiol action in vivo and 1 h of tissue incubation with labelled leucine. This negative result summarizes a search among different nuclear protein fractions using various procedures; nor was induced protein observed in mitochondrial and microsomal pellets. Contrary to these negative findings, slight changes of histone labelling were observed under the experimental conditions used to demonstrate induced protein. In addition histone acetylation was increased after 1 h of estradiol action in vivo and 15 min tissue labelling in vitro with radioactive acetate. Furthermore, an increase in total protein synthesis between 0 and 2 h after estradiol action was observed, the relative increase of incorporation of radioactive leucine into protein of estradiol‐treated vs non‐stimulated uteri being corrected for variations of the acid‐soluble radioactive leucine pool. Attempts to obtain an early and discrete induced protein with androgens in prostate and seminal vesicles of immature or castrated rats after different times of exposure to testosterone, androstanolone and estradiol have been unsuccessful. The contribution of both negative and positive findings in steroid‐induced early protein synthesis is discussed in the context of the current knowledge of hormone action.

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New Look at the Very Early Steps of Oestrogen Action in Uterus

Cited by 70 publications

References 27 publications

Estrogens and Antiestrogens

Estrogens and Antiestrogens

Separation of "estrogen-induced" protein from phosphoprotein phosphatase activity of immature rat uterus.

Steroid‐Induced Early Protein Synthesis in Rat Uterus and Prostate

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