Mechanism of Action of the Female Sex Hormones

Jensen, Elwood V.; DeSombre, Eugene R.

doi:10.1146/annurev.bi.41.070172.001223

Cited by 746 publications

(159 citation statements)

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“…These regulatory proteins synthesized in the cytoplasm then move into the nucleus and bind to the chromatin, causing a further increase in RNA synthesis. The general features of this model are similar to those proposed for estrogen action by O'Malley, Jensen, and Gorski, and their respective coworkers (1,15,24). Our model, however, has as an additional feature an emphasis on an early induction of specific regulatory proteins necessary for the complete genomic response to the hormone.…”

Section: Discussionsupporting

confidence: 58%

“…The frozen powder was homogenized in 20 ml of saline-EDTA (0.075 M NaCl, 0.025 M EDTA, pH 8) with a polytron PT 20 tissue disintegrator run at 60 V for 30 sec, and the homogenate was filtered through four layers of nylon bolting cloth. A pellet was collected by centrifugation at 1500 X g for 15 sion was centrifuged at 800 X g for 2.5 min, the pellet was discarded, and the supernatant fraction was used immediately for the extraction of chromosomal proteins.…”

Section: Methodsmentioning

confidence: 99%

“…The molecular weights of the protein standards used for calibration were as follows: thyroglobulin, 160,000; bovine serum albumin, 68,000; pyruvate kinase, 57,000; ovalbumin, 43,000; pepsin, 35,000; chymotrypsinogen, 25,500; hemoglobin, 15 from uterine chromatin of ovariectomized rats treated for S hr with estrogen. Reversal of the isotopes of the precursors used to label control and experimental uteri gave comparable results.…”

Section: Methodsmentioning

confidence: 99%

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Effect of extradiol-17beta on the synthesis of specific uterine nonhistone chromosomal proteins.

Cohen¹,

Hamilton²

1975

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

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The synthesis of specific nonhistone chromosomal proteins in the uterus of the ovariectomized rat was examined as a function of time after treatment with estradiol-17fl. Sequential stimulations in the rates of synthesis of at least five nonhistone chromosomal proteins having molecular weights of 96,000, 70,500, 29,400, 20,700, and 16,400, respectively, were observed. The rate of synthesis of the nonhistone chromosomal protein having a molecular weight of 70,500 was increased at 1 hr after hormone treatment. This was the first nonhistone chromosomal protein to be induced by estrogen, and its induction was blocked by pretreatment with actinomycin D. The data reported suggest but do not prove that this protein is the 4.5 S estrogen receptor, and that it is the induced nuclear acidic protein described earlier by Teng and Hamilton. The rates of synthesis of the nonhistone proteins with molecular weights of 96,000, 29,400, 20,700, and 16,400 were increased at 3, 5, 24, and 24 hr, respectively, after hormone treatment. the end of the incubation period, the two groups of uteri were pooled, rinsed thoroughly with ice-cold 0.9% NaCl, and rapidly frozen on dry ice. Under these conditions the incorporation of labeled amino acids into uterine protein was linear for incubation periods of at least 3 hr.Cell Fractionation. Uterine chromatin was prepared by a modification of the method of Bonner et al. (10). All procedures were carried out at 0-40 unless otherwise indicated. Frozen uteri were placed in a stainless steel tissue pulverizer chilled to -80°and crushed to a powder. The frozen powder was homogenized in 20 ml of saline-EDTA (0.075 M NaCl, 0.025 M EDTA, pH 8) with a polytron PT 20 tissue disintegrator run at 60 V for 30 sec, and the homogenate was filtered through four layers of nylon bolting cloth. A pellet was collected by centrifugation at 1500 X g for 15 min in the Sorvall RC-2 centrifuge. The pellet was washed once with the saline-EDTA containing 0.5% Triton X-100, and then once with the saline-EDTA alone. It was then washed three times with 0.01 M Tris-HCl (pH 8) by centrifugation at 4300 X g, 10,000 X g, and 17,000 X g. The

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Section: Discussionsupporting

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effect of extradiol-17beta on the synthesis of specific uterine nonhistone chromosomal proteins.

Cohen¹,

Hamilton²

1975

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

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“…Specific high affinity cytoplasmic receptor proteins for steroid hormones, whose existence was first demonstrated by Jensen et al (1), are responsible for this phenomenon. These receptor proteins, of which there is one specific type for each steroid hormone, are essential components in the chain of action of steroid hormones in the target cell.…”

Section: Introductionmentioning

confidence: 95%

Estrogen and Progesterone Binding Proteins in Normal Human Myometrium and Leiomyoma Tissue

Pollow¹,

Geilfuss²,

Boquoi³

et al. 1978

Clinical Chemistry and Laboratory Medicine

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Summary: The occurrence and characteristics of macromolecular components of normal human myometrium and leiomyoma which bind [ 3 H]estradiol and [ 3 H]progesterone were investigated, employing dextran coated charcoal, density gradient centrifugation and gel filtration techniques.On sucrose density gradient centrigugation, [ 3 H]progesterone was bound by macromolecules with sedimentation rates of about 4 S and 8 S.The major [ 3 H]progesterone binding component had a sedimentation coefficient of about 4 S, which contained specific and nonspecific binding sites.Sedimentation patterns as well as elution profiles from agarose gel revealed a striking similarity between biochemical properties of the progesterone receptors from normal myometrium and leiomyomas of the same organ.Both progesterone and estradiql receptor change in concentration during the normal menstrual cycle. During the early proliferative phase the number of estradiol receptor binding sites was highest; after ovulation, a rapid decrease of estradiol receptor level was seen. On the other hand, using [ 3 H]progesterone as the ligand, the highest receptor concentration was found at midcycle.The leiomyoma steroid hormone receptor levels were compared with those in normal myometrium. Whereas leiomyoma exhibited higher estradiol binding capacity, the concentration of progesterone receptors was low in fibroid tumors. In normalem Gewebe variieren die Prqgesterqn-sowie Östradiol-Rezeptorkonzentrationen in der Cytoplasmafraktion. Die höchsten Östradiol-Rezeptorbindungsaktivitäten wurden während der frühen Proliferationsphase beobachtet; nach Oviüation kommt es zu einem rapiden Abfall der Östradipl-Rezeptorkohzentration. Die höchsten ProgesteronRezeptorkonzentratipnen zeichneten sich ab in der Mitte des Menstruationszyklus zum Zeitpunkt der Ovulation. Myome waren charakterisiert durch hohe Östradiql-Bindungskäpazität und eine niedrigere Progesteron-Rezeptorkonzentration. Östrogen-und Progesterön-Rezeptören in normalem Human-Myometrium und Myomen

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“…This association alters the transcriptional controls and allows the synthesis of new mRNA species. The new mRNAs are eventually translated into new proteins that are often specific for the hormone-stimulated tissue (1,3,5,6). The target cell nuclear acceptor is selective in that the nuclei of responsive cells accept more hormone-cytosol protein complex than the nuclei of tissues refractory to the action of steroid hormones (7,8).…”

mentioning

confidence: 99%

Acceptor proteins in rat androgenic tissue chromatin.

Klyzsejko-Stefanowicz¹,

Chiu²,

Tsai³

et al. 1976

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

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Fractionation of chromatin into urea-soluble chromosomal nonhistone proteins (UP), histones (HP), and DNA-associated nonhistone proteins (NP) revealed that the NP fraction from testicular and prostatic chromatin contains organ-specific acceptors for complexes of 5a-dihydrotestosterone (17j3-hydroxy-5a-androstan-3-one) and its receptor. This acceptor capacity of androgenic tissue chromatin could be transferred to chromatins from non-target tissues with the NP fraction of DNA-associated proteins. Phosphorylation of chromatin enhanced its hormone-receptor binding capacity. According to current views, early steps in the action of steroid hormones on their target tissues involve the association of the steroid hormone with cytoplasmic receptor, transport of this complex from cytoplasm into the nucleus, and, finally, its association with specific acceptor sites on chromatin (1-4). This association alters the transcriptional controls and allows the synthesis of new mRNA species. The new mRNAs are eventually translated into new proteins that are often specific for the hormone-stimulated tissue (1,3,5,6). The target cell nuclear acceptor is selective in that the nuclei of responsive cells accept more hormone-cytosol protein complex than the nuclei of tissues refractory to the action of steroid hormones (7,8). Recent years have seen the accumulation of considerable information concerning the steroid hormone-cytoplasmic receptor interactions in different types of tissue. After the hormone interacts with cytoplasmic receptor, the hormone-protein complex moves to the nucleus, where it is incorporated into chromatin. Liao and Fang (1) coined the term "acceptor protein" for the nuclear acceptor molecule. The acceptor protein fraction was isolated from prostate (9) and found to be heat labile and tissue specific, and could be transferred from the chromatin of one tissue to another with the fraction of chromosomal nonhistone proteins (3, 7). We report here the results of our studies on chromatin acceptor(s) in rat prostate and testis. MATERIALS AND METHODSProstatp, testis, liver, and pancreas from male Sprague-Dawley rats (125-150 g) were homogenized in ice-cold 0.25 M sucrose, 5 mM MgCl2, and 2 mM 2-mercaptoethanol in 20 mM Tris-HCI buffer, pH 6.8. The homogenate was centrifuged at 800 X g for 10 min. The crude nuclear pellet was purified by rehomoAbbreviations: SSC, standard saline citrate (150 mM NaCl, 15 mM sodium citrate); UP, chromosomal nonhistone proteins soluble in urea at low ionic strength; HP, histones; NP, DNA-binding chromosomal nonhistone protein fraction; DHT, 5a-dihydrotestosterone (17f,-hydroxy-5a-androstah-3-one). After incubation with labeled hormone, the cytosol-hormone complex was fractionated with (NH4)2SO4 (0-33% saturation). The active fraction was freed from unbound hormone by gel -filtration on a Sephadex G-25 column (1 X 24 cm). Sucrose density gradient analysis of the purified [3H]DHT-receptor complex showed that essentially all the radioactivity was associated with the receptor protein peak ...

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Mechanism of Action of the Female Sex Hormones

Cited by 746 publications

References 1 publication

Effect of extradiol-17beta on the synthesis of specific uterine nonhistone chromosomal proteins.

Effect of extradiol-17beta on the synthesis of specific uterine nonhistone chromosomal proteins.

Estrogen and Progesterone Binding Proteins in Normal Human Myometrium and Leiomyoma Tissue

Acceptor proteins in rat androgenic tissue chromatin.

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