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At least 325 records · Page 18Linked to original sources
PubMed1980

The presence of progesterone receptors in the sexual skin of the monkey.

R5020(17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione)-binding components with sedimentation coefficient of 8S were detected in sexual skin cytosols from estrogen-primed ovariectomized Japanese monkey (Macaca fuscata fuscata). In contrast, little 8S binding was found in similar preparations from the abdominal skin. The dissociation constants and the number of binding sites of the components were 1.6 x 10(-10)M and 36 fmoles/mg cytosol protein, respectively. The 8S binding components were specific for progestational compounds. Incubation with pronase abolished the 8S binding. Thermal experiments revealed the thermolabile nature of the components. Moreover, the concentration of the R5020-binding components was markedly increased by estradiol-17 beta 3-benzoate injections. We conclude from these results that the cytosols from the sexual skin of estrogen-primed female monkeys contain progesterone receptors.

Animals↗
PubMed1980

Analysis of progesterone receptor binding in the ovine uterus.

The appropriate conditions for the measurement of ovine uterine cytoplasmic progesterone receptors (PR) have been determined to be 20 nM 3H-progesterone (3H-P4) with and without a 100-fold excess of non-radioactive progesterone (P4) 0-4 degrees C and 4 h of incubation. Under these conditions PR readily exchanged bound progesterone for progesterone added during the assay. This exchange occurred even when saturating concentrations of P4 were present. The progestins, R5020 and P4, effectively competed for the ovine uterine PR binding while non-progestin steroids and diethylstilbestrol failed to compete for the PR binding. The dissociation constant (Kd) measured for the 3H-P4 binding was 1.60 x 10-9 M indicating that the 3H-P4 binding was of high affinity. The levels of PR and the dissociation constant measured using 3H-R5020 in place of 3H-P4 were similar indicating a lack of corticosteroid binding globulin (CBG)-like binding in the ovine uterus.

Animals↗
PubMed1982

Rat ovary glucocorticoid receptor: identification and characterization.

A soluble, thermolabile protein with characteristics typical of glucocorticoid receptors has been identified in the ovaries of estrogen-stimulated hypophysectomized immature rats. After the incubation of 3H- dexamethasone with ovarian cytosol, fractionation on a Sephadex G-200 column reveals a peak of radioactivity which elutes at the void volume. This peak, which represents saturable 3H-dexamethasone binding, disappears following heating (4 degrees C X 15 min) or treatment of the cytosol with pronase. Scatchard analysis of the 3H-dexamethasone binding to cytosol shows it to be high affinity (Kd=5.1 nM) and saturable, with 327 fmol binding sites/mg cytosol protein. Binding site number rises linearly with increasing cytosol protein concentrations. The relative abilities of various steroids to inhibit 3H-dexamethasone binding are: triamcinolone acetonide greater than or equal to dexamethasone greater than cortisol = progesterone greater than dihydro-testosterone greater than estradiol. This binding protein sediments at 9 S on a sucrose gradient, has a mean Stokes radius of 105 A on gel exclusion chromatography, and has a calculated molecular weight of 388,000 daltons and a frictional ratio of 2.1. 3H-Dexamethasone is not metabolized and does not bind specifically to serum. We have identified a protein in the rat ovary with characteristics of a glucocorticoid receptor and propose that this protein may be responsible for mediating direct effects of glucocorticoids on the ovary.

Animals↗
PubMed1982

Characteristics of the nuclear translocation of progesterone receptor in fetal guinea pig uterus "in vivo", "in vitro" and in organ culture.

The translocation of progesterone receptor from the cytosol into the nucleus was studied under "in vivo" and "in vitro" conditions in the uteri of guinea pig fetuses exposed to progesterone or a synthetic progestin, R5020. Progesterone treatment of estrogen-primed fetuses leads to a rapid (before 1h) transfer of cytosol progesterone receptor into the nucleus which is, however, short-lived (less than 3h). A rapid decrease in the retention of the estrogen receptor in the nucleus also occurs. In the "in vitro" incubations of whole fetal uteri, translocation of progesterone receptor is temperature-dependent and specific for progesterone and R5020; estradiol and cortisol have no effect. Putative progesterone receptors can also be induced in explants of fetal guinea pig uteri in organ culture which translocate from the cytosol into the nucleus under the same "in vitro" conditions as in whole uteri. Fetal uterine progesterone receptor, either stimulated "in vivo" by estrogen-priming or induced in organ culture, translocates from the cytosol into the nucleus and this process seems to be accompanied by a decrease in retention of the estrogen receptor in the nucleus which appears to be the mechanism by which progesterone antagonises estrogen action in fetal guinea pig uterus.

Animals↗
PubMed1982

Progestin binding in mammary tissue of prepartum, nonlactating and postpartum, lactating cows.

Binding of [3H]R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3, 20-=dione) to bovine mammary cytosol indicated the presence of progestin binding sites of high-affinity and low-capacity in tissue from prepartum, nonlactating and from postpartum, lactating cows. To prevent binding of [3H]R5020 to glucocorticoid binding sites, a 200-fold molar excess of nonradioactive cortisol was included during all incubations, thus specific binding was limited to progestin binding sites. Nonradioactive R5020 and progesterone effectively inhibited [3H]R5020 binding to progestin binding sites, while estradiol-17 beta, dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one), dexamethasone (9-fluoro-11 beta, 17, 21-trihydroxy-16 alpha methyl-1,4-pregnadiene-3,20-dione) or additional cortisol were ineffective. Dissociation constants for especially bound [3H]R5020 in cytosol from mammary tissue of nonlactating and lactating cows were nearly identical, averaging 1.9 (+/- 0.3) and 0.8 (+/- 0.2) x 10(-9)M, respectively. However, binding capacities (fmol/mg cytosolic protein) were greater in cytosol from prepartum, nonlactating (179 +/- 53) than postpartum, lactating (41 +/- 15) cows. Specific binding components in cytosol from lactating cows sedimented iun the 6-7S region on linear sucrose density gradients. When subjected to isoelectric focusing, specific binders with isoelectric points (pI) of approximately 6.1, 7.9 and 8.3 were resolved. The decrease in number of binding sites during lactation was due to the virtual absence of the anionic binding species, suggesting that their presence is necessary for progesterone to inhibit milk secretion.

Animals↗
PubMed1983

Diethylpyrocarbonate, a histidine selective reagent, inhibits progestin binding to chick oviduct cytosol.

In this report we describe experiments showing that diethylpyrocarbonate, a histidine selective reagent, inhibits progestin binding to the chick oviduct progesterone receptor. Because this inhibition is reversed by hydroxylamine, we suggest that the chick oviduct progesterone receptor contains one or more histidine residues that regulate progestin binding. We also find that the progestin R5020 protects the progesterone receptor from diethylpyrocarbonate mediated inhibition of progestin binding. From this we infer that the progestin binding site contains a histidine residue(s) important for progesterone binding to its receptor in chick oviduct.

Animals↗
PubMed1983

Ligand-induced change in sedimentation behavior of human progestin receptors.

We determined the effect of ligand binding on the sedimentation behavior of cytosolic progestin receptors in human uterine leiomyomata, normal endometria and myometria. When cytosols were prelabeled with the tritiated progestin R5020, 4.4S and 7-8S receptors were demonstrated in all three uterine tissues; with postlabeling of fractionated gradients, 4.4S and 9-10S receptors were present. Sodium molybdate (20 mM) blocked the ligand-induced conversion of 9-10S to 7-8S receptors. The relative amount of 7-8S receptor increased with increasing amounts of ligand and time of incubation with ligand (up to 5 hrs); the amount of 9-10S receptor decreased with time. These data indicate that ligand binding to human uterine progestin receptors induces a change from a 9-10S to 7-8S form of receptor. Since molybdate blocks transformation of receptors and the ligand effect on receptor sedimentation, ligand binding to 9-10S receptor and the consequent conversion to 7-8S receptor may be a step preceding transformation of progestin receptors.

Centrifugation, Density Gradient↗
PubMed1984

Progestin receptors in dispersed rat anterior pituitary cells: enriched binding in lactotrope fractions.

Cytosolic progesterone and R5020 binding activities were demonstrated in Pronase-dispersed anterior pituitary cells from estrogen-primed ovariectomized and adrenalectomized rats. Pronase-dispersed pituitary cells were also separated into six cellular fractions on the basis of size and density by sedimentation velocity at unit gravity in a BSA gradient. Fractions enriched in lactotropes or gonadotropes were identified by the cellular contents of radioimmunoassayable prolactin and LH, respectively. Cytosolic progestin receptors appeared to be predominantly associated with lactotrope-rich fractions. Since there was some cross-over between the LH and prolactin enriched fractions, progestin receptors may also be associated with a subpopulation of gonadotropes, as well.

Animals↗
PubMedDate not supplied

ORG-2058 as a ligand in the assay of progesterone receptor in breast cancer.

Tritiated [(16 alpha-ethyl-21-hydroxy-19-nor-pregn-4-ene-3,20-dione)-6,7-3H] (ORG-2058) and 17,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione (R5020) were compared as ligands in the assay of progesterone receptor in human and rat breast tumors. We found that ORG-2058 is a better ligand because of its low nonspecific binding. Most of the nonspecific binding of the other ligand R5020, is to proteins which bind corticosteroids. In cancerous tissue ORG-2058 binds to progesterone receptor linearly in a range of protein concentrations which are normally used in the receptor assay. On the other hand, R5020 exhibits binding linearity over a narrower protein concentration in many tumor biopsies, which may cause severe limitation in the assay procedure or frequent underestimation of receptor content.

Animals↗
PubMedDate not supplied

Binding of (3H)7 alpha,17 alpha-dimethyl-19-nortestosterone (mibolerone) to progesterone receptors: comparison with binding of (3H)R5020 and (3H)ORG2058.

The binding characteristics of (3H)7 alpha,17 alpha-dimethyl-19-nortestosterone [3H)DMNT) to progesterone receptors (PgR) of calf uterine tissue cytosol were determined and compared to those of the synthetic progestins (3H)ORG2058 and (3H)R5020. Scatchard plot analysis of the equilibrium binding data showed that (3H)DMNT binds to calf uterine PgR with a KD of 2.35 +/- 1.1 nM. This value is slightly higher than that of (3H)R5020 (KD = 1.16 +/- 0.4 nM) and (3H)ORG2058 (KD = 1.04 +/- 0.65 nM). Analysis of dissociation kinetics showed that (3H)DMNT dissociates much more rapidly from the receptor than the other two ligands. Competition experiments showed that ORG2058 has a lower inhibition constant (Ki) than DMNT. Sucrose density gradient (SDG) analysis of PgR showed that (3H)ORG2058-PgR complexes sediment as 8S, (3H)R5020-PgR complexes sediment as 8S and 4S, and (3H)DMNT-PgR complexes sediment as 8S entities along with dissociated (3H)steroid. These data suggest that (3H)DMNT binds to PgR with lower affinity than (3H)ORG2058 and (3H)R5020. The number of binding sites detected with (3H)DMNT are significantly lower than those measured with (3H)ORG2058.

Animals↗
PubMedDate not supplied

Binding of 5 alpha-dihydroprogesterone and other progestins to female rat anterior pituitary nuclear extracts.

The specific binding of 5 alpha-dihydroprogesterone (5 alpha-DHP), progesterone and R5020 to anterior pituitary nuclear extracts was studied using ovariectomized rats treated with estradiol benzoate and progesterone. The binding equilibrium association constant for 5 alpha-dihydroprogesterone with different preparations of nuclear extract ranged from 4.0 +/- 0.54 microM-1 to 59 +/- 10 microM-1. The association constants for progesterone and R5020 were 0.39 +/- 0.81 nM-1 and 1.5 +/- 0.15 nM-1, respectively. The binding of 5 alpha-DHP was specific in that it could be competed only by R5020, progesterone and 5 alpha-DHP and not by other progesterone metabolites and other hormonal steroids tested. With [3H]-progesterone and [3H]R5020 as ligands the most efficient competitors also were R5020, progesterone and 5 alpha-DHP. Estrogen priming of ovariectomized rats consistently and significantly increased the number of binding sites for all three progestins and subsequent progesterone treatment enabled their detection at higher levels in the nuclei.

5-alpha-Dihydroprogesterone↗
PubMed1993

Nuclear receptors for progesterone and estradiol in the guinea pig uterine compartment during gestation.

Because progesterone suppresses myometrial contractility, the assumption is often made that the withdrawal of this steroid is a prerequisite for parturition. However, steroid patterns in maternal blood of the guinea pig do not consistently change with impending parturition and it has been claimed that progesterone does not suppress guinea pig myometrial contraction. The present study investigated progesterone and estrogen nuclear receptor binding in myometrium, endometrium, and chorion between 32 days of gestation and delivery at 67-71 days. Binding characteristics and behavior during sedimentation in sucrose density gradients were typical of the steroid hormone receptor family. Decreased progestin binding occurred in the myometrium, from a high of 1600 fmol/mg DNA at 49-51 days to a low of 450 fmol/mg DNA (P < 0.01) on the day of detectable pubic relaxation. This decrease commenced at 60-63 days just before the onset of relaxation. A similar, though less well defined change occurred in endometrium. Estradiol nuclear receptor binding in myometrium remained at about 350 fmol/mg DNA from 32 days until 1-2 days pre-partum when it increased to about 650 fmol/mg DNA (P < 0.05). Estradiol binding in endometrium showed an inconsistent pattern and chorion binding for both progestin and estradiol was low and unremarkable. We conclude that there is a potential for decreased progesterone effect in myometrium at about one week before delivery and increased estrogen action in that tissue immediately before delivery.

Animals↗
PubMed1995

In vitro labeling of gonadal steroid hormone receptors in brain tissue sections.

Autoradiographic methods have been developed for measurement of gonadal steroid receptors in situ in brain tissue sections. Based on principles established previously for estrogen receptors in the rat brain using a 125I-labeled ligand, procedures have been developed for in vitro labeling of estrogen, androgen, and progestin receptors with commercially available tritiated ligands. Addition of protamine sulfate to the incubation buffer precipitates the receptors in situ in the tissue sections, allowing them to be detected autoradiographically after incubation with labeled steroid and subsequent washing to remove unbound and nonspecifically bound ligand. Occupied and unoccupied estrogen receptors can be measured selectively using appropriately modified incubation conditions. In the case of androgen and progestin receptors, unoccupied receptors are readily detected by in vitro labeling of tissue sections, but occupied receptors do not appear to label efficiently. Preliminary data suggest that these methods should be equally applicable to a variety of laboratory animals, including the rat, mouse, guinea pig, and monkey.

Animals↗
PubMed1986

Steroid-receptor complexes and their interaction with the rat liver nuclei during ontogenesis.

Steroid-receptor complexes (SRCs) (glucocorticoids, estrogens and progestins) are isolated from rat liver and purified 1500-2000-fold. Both the initial cytosol complexes and those purified 2000-fold were characterized by gel filtration on Sephadex G-100 and DEAE-cellulose chromatography. The purified rat liver SRCs were used for binding to the isolated liver nuclei from rats of different ages (1.5, 6, 12, 24 months). Binding of progestin and estrogen-receptor complexes from rat liver to homological nuclei of 1.5-month-old rats is maximum, no distinct differences being found in the case of glucocorticoid-receptor complexes. SRC binding to the nuclei progressively declines with age, reaching its minimum by 24 months. The revealed differences in SRC binding by the nuclei of animals of different ages seem to be the basis of the hormone-induced changes in the organism functioning at various stages of ontogenesis.

Aging↗
PubMed1987

Androgen receptor binding activity in meningiomas.

Analyses of androgen receptor binding activity in 54 intracranial, intraspinal, and metastatic meningiomas were performed with a specific radioligand binding technique using [3H]R 1881 as radioligand. [3H]R 5020 was used for the concurrent determination of progesterone receptor binding activity. Moderate concentrations of androgen receptors (33.4 +/- 5.4 fmol/mg protein) were detected in 35 (65%), whereas high levels of progesterone binding components (236 +/- 35 fmol/mg protein) were demonstrated in 48 (89%) tumors. The androgen receptor binding activity was positively correlated with the progesterone receptor binding activity (rs = 0.38, p less than 0.05). This relationship is suggestive of an androgen regulation of the progesterone receptor via the androgen receptor system. The presence of androgen and progesterone receptors in a large proportion of meningiomas, and the tendency for a dependence of androgen receptor and progesterone receptor binding activity on the histological subtype could have implications for tumor therapy.

Estrenes↗
PubMed1992

Effect of the progesterone antagonist RU486 on human myometrial spontaneous contractility and PGI2 release.

We studied the effect of antiprogesterone RU 486 on spontaneous uterine contractility and PGI2 release with human myometrial strips superfused "in vitro". A decrease of PGI2 release into the superfusion medium was observed after 20 min superfusion. The inhibition was dose-dependent and reversible. After 20 min washing with tyrode medium without RU 486, the uterine strips recovered their initial rate of release. R5020, a progesterone agonist, did not affect PGI2 release nor dexamethasone and testosterone. Parallel to the decrease of PGI2 observed during RU 486 superfusion, the uterine spontaneous contraction frequency decreased, while the amplitude and duration of contractions increased. The alteration of uterine contractility was also rapid, dose-dependent and reversible. Modification of uterine strip spontaneous contractility, similar to those induced by RU 486, were also observed with superfusions of R5020 at concentrations as low as 10(-9)M, dexamethasone (10(-8)M), but not with superfusions of testosterone. These observations are not in favour of a progesterone-receptor mediated effect of RU 486 in our model. The mechanism of action may be related to the antiprogesterone specific structure i.e. the bulky substituent at the C-11 position. The RU 486 effect on uterine strip contractility, mimicked by other steroids, could point to a non-specific lipid/membrane interaction. However, the fact that testosterone did not affect motility, may indicate a possible specificity of steroids having a 3 oxo pregnene structure.

Adult↗
PubMed1982

Variant T47D human breast cancer cells with high progesterone-receptor levels despite estrogen and antiestrogen resistance.

In target tissues for estrogen, including breast cancer cells, the synthesis of progesterone receptors (PRs) is controlled by estradiol acting through estrogen receptors (ERs). We describe studies with T47D human breast cancer cells, whose PRs are not regulated by estradiol, though present in extraordinary amounts (300,000 sites per cell). These cells have no ERs sedimenting at 8S on sucrose density gradients, and no unfilled cytoplasmic or nuclear ERs; some apparently hormone-filled nuclear sites, with KD congruent to 0.7 nM, can be demonstrated by exchange. The nuclear ER sites are not processed after estradiol treatment. Nafoxidine, however, doubles nuclear estrogen binding in 6 hr, in a cycloheximide-insensitive step that may represent a reversal of processing. T47D cells are profoundly resistant to estrogens and antiestrogens; estradiol does not stimulate PRs, and nafoxidine concentrations that are cytotoxic to ER-positive cells have no effect on cell growth or on PR levels. Yet the PRs are normal by several criteria, and they can be stoichiometrically translocated to, and extracted from, nuclei in the first 3 min after progesterone addition. If progesterone treatment exceeds 10 min, rapid nuclear turnover prevents quantitative PR recovery. Cytoplasmic PRs are replenished in 10 to 24 hr, and this cycloheximide-sensitive step is also estrogen- and nafoxidine-resistant. However, despite their insensitivity to estradiol or antiestrogen, PRs are not constitutively synthesized; 5-bromodeoxyuridine and sodium butyrate can selectively inhibit PR production. Thus, since PRs retain some characteristics of inducible proteins, the persistent nuclear estrogen-binding sites may be stimulating PRs continuously, even in the absence of exogenous estradiol.

Breast Neoplasms↗
PubMed1994

The establishment of the long terminal repeat of the mouse mammary tumor virus into CV-1 cells allows a functional analysis of steroid receptors.

To analyze in situ the effects of mineralocorticoid receptor (MR) on the nucleo-protein organization of the target MMTV promoter, we have established a new cell line by integrating in CV-1 cells a construct containing the long terminal repeat of the mouse mammary tumor virus (MMTV-LTR). The MMTV-LTR contains glucocorticoid response elements (GREs), known to interact with MR. CV-1 cells were selected because they lack glucocorticoid receptor (GR). The absence of GR in the host cell line allows the selective analysis of transcription activation by aldosterone in cells expressing MR transiently. The CV-1 cells were transfected with the construct pMAMneoCAT, a plasmid containing the MMTV promoter driving the chloramphenicol acetyl transferase (CAT) gene and a gene for neomycin selection. A neomycin-resistant clone (M8), which contains two copies of the unrearranged construct was characterized. The integrated MMTV promoter is functional, as demonstrated by the induction of the CAT activity upon addition of aldosterone, dexamethasone, and R5020 to M8 cells transiently transfected with MR, GR, and progesterone receptor (PR) expression vectors, respectively. Induction of the CAT activity by dexamethasone or progesterone was 2 to 3-fold higher than by aldosterone. These differences in CAT activities were not related to differences in the levels of receptor expression. In the transiently transfected M8 cells, MR and PR contents were similar (50-70 fmol/mg protein) while GR content was higher (250 fmol/mg protein). Thus, this new cell line M8, provides a useful tool for selectively studying the effect of MR on a target promoter organized into chromatin.

Aldosterone↗