scholarly journals The unoccupied nuclear oestradiol receptor in the rat uterus and hypothalamus during the oestrous cycle

1981 ◽  
Vol 194 (3) ◽  
pp. 667-671 ◽  
Author(s):  
S Thrower ◽  
C Neethling ◽  
J O White ◽  
L Lim
Keyword(s):  
Nuclear Receptor ◽  
Oestrogen Receptor ◽  
Oestrous Cycle ◽  
Oestrogen Receptors ◽  
Rat Uterus ◽  
Immature Rat ◽  
High Affinity ◽  
Receptor Component ◽  
Cyclic Changes

The nuclear oestrogen receptor population in the rat uterus contained an unoccupied receptor component that bound oestradiol with the high affinity (Kd congruent to 0.5 nM) characteristic of oestrogen receptors. This unoccupied receptor was present at all phases of the oestrous cycle. Its content changed in parallel with that of the total nuclear receptor during the cycle. Oestradiol administration to the immature rat resulted in increases in the uterine content of long-term nuclear receptors (i.e., those still present 8 h after administration); these increases were due to occupied oestrogen receptors, since the content of unoccupied receptor was unchanged. Our previous experiments [White & Lim (1980) Biochem. J. 190, 833-837] have shown in contrast, that oestradiol administration results in an increase in the content of unoccupied nuclear receptor in the hypothalamus. However, as in the uterus, similar cyclic changes in the content of unoccupied nuclear receptor occurred in parallel with those of the total nuclear receptor population in the hypothalamus. Differences and similarities between the unoccupied nuclear receptor of the uterus and hypothalamus are briefly discussed.

scholarly journals Nucleo-cytoplasmic relationships of oestrogen receptors in rat liver during the oestrous cycle and in response to administered natural and synthetic oestrogen

1980 ◽  
Vol 190 (1) ◽  
pp. 17-25 ◽  
Author(s):  
W Marr ◽  
J O White ◽  
M G Elder ◽  
L Lim
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Rat Liver ◽  
Fold Increase ◽  
Oestrous Cycle ◽  
Physiological Changes ◽  
Oestrogen Receptors ◽  
High Affinity ◽  
Cyclic Changes ◽  
Similar Affinity

Oestrogen receptors were measured in the cytosolic and purified nuclear fractions of rat liver. Both cytosolic and nuclear receptors bind oestrogen with high affinity (Kd = 1.47 and 2.28 nM respectively) and specificity similar to that of receptors in order oestrogen-target tissues such as the uterus. During the 4-day oestrous cycle the receptor content and distribution between cytosol and nucleus did not vary; in particular, the content of nuclear receptor did not appear to fluctuate in concert with known cyclic changes in the concentration of plasma oestrogen. Injection of 50 micrograms of oestradiol-17 beta or 10 micrograms of ethynyloestradiol resulted in a 4–6-fold increase in the nuclear receptor content, with a concomitant decrease in the unoccupied-receptor content of cytosol 1 h after injection. The nuclear receptors present after injection bind oestrogens with similar affinity (Kd = 2.78 nM) and specificity to receptors present in uninjected animals. The administration of lower doses of either oestrogen was less effective in producing increases in nuclear receptor content. Hence there is apparently substantial translocation of receptor to the nucleus in response to hyperphysiological doses of oestrogen, but not to the physiological changes in plasma oestrogen concentrations during the oestrous cycle. The response to exogenous oestrogens is discussed in relation to the clinical use of synthetic oestrogens and progestogens.

EFFECT OF AN INTRA-UTERINE DEVICE ON INTRACELLULAR RELATIONSHIPS OF THE UTERINE OESTROGEN RECEPTOR, PARTICULARLY DURING PREGNANCY

1980 ◽  
Vol 87 (3) ◽  
pp. 357-364 ◽  
Author(s):  
LESLIE MYATT ◽  
GAUTAM CHAUDHURI ◽  
M. G. ELDER ◽  
LOUIS LIM
Keyword(s):  
Protein Synthesis ◽  
Nuclear Receptor ◽  
Oestrogen Receptor ◽  
Oestrous Cycle ◽  
Blastocyst Implantation ◽  
High Concentrations ◽  
Cyclic Changes ◽  
And Control ◽  
Nuclear Content

The presence of an intra-uterine device in the rat results in a lower nuclear concentration of the oestrogen receptor in the treated horn at pro-oestrus when it is compared with the contralateral control horn. This effect was also seen after the administration of hyperphysiological doses of oestradiol and when the horn was exposed in vitro to high concentrations of oestradiol. The cyclic changes during the oestrous cycle in the activity of the oestrogen-induced enzyme peroxidase were similar in the treated and control horns. These observations have discounted the possibility that the relatively lower nuclear receptor content in the treated horn at pro-oestrus was due to a decreased exposure to oestrogen. A significantly lower nuclear content was also observed in the treated horn on days 4 and 5 of pregnancy. This was not associated with a deficiency in cytosol receptor content which increased concurrently with that of the control horn in the 6 days of pregnancy that were studied. The proportional content of the putative cytosol factor implicated in receptor translocation was similar in both horns, increasing on days 4 and 6 in concert with reported changes in 'induced protein' synthesis. There appeared to be reduced levels of nuclear receptor at a time when blastocyst implantation normally occurs.

scholarly journals A comparison of the relationships between progestin receptors and oestrogen receptors in neural and non-neural target tissues of the rat during the oestrous cycle

1980 ◽  
Vol 190 (3) ◽  
pp. 691-695 ◽  
Author(s):  
S Thrower ◽  
L Lim
Keyword(s):  
Cerebral Cortex ◽  
Oestrogen Receptor ◽  
Oestrous Cycle ◽  
Oestrogen Receptors ◽  
Progestin Receptors ◽  
Progestin Receptor ◽  
Cyclic Changes ◽  
Relationship Of ◽  
The Relationship

Similar cyclic changes in the content of nuclear oestrogen receptor occurred in the hypothalamus, cerebral cortex, uterus and pituitary during the oestrous cycle. The relationship of the unoccupied to the total nuclear oestrogen receptor at each phase was similar in all these tissues. However, cyclic changes in the content of the cytosol progestin receptor occurred only in the uterus and pituitary (where they paralleled changes in the nuclear oestrogen receptor), but not in the hypothalamus or cerebral cortex.

scholarly journals The oestrogen receptor in the rat uterus in relation to intra-uterine devices and the oestrous cycle

1978 ◽  
Vol 176 (2) ◽  
pp. 523-529 ◽  
Author(s):  
L Myatt ◽  
G Chaudhuri ◽  
M G Elder ◽  
L Lim
Keyword(s):  
Nuclear Receptor ◽  
Oestrogen Receptor ◽  
Dissociation Constants ◽  
Intrauterine Device ◽  
Oestrous Cycle ◽  
Rat Uterus ◽  
Receptor Complexes ◽  
Wet Weight ◽  
Cytosolic Receptor

We investigated the binding characteristics, content and intracellular distribution of nuclear and cytosolic oestrogen receptors in the uteri of rats bearing a unilateral intrauterine device, fitted 14–18 days earlier, at four phases of a 5-day oestrous cycle. The patterns of changes in wet weight and content of cytosolic and nuclear receptor that normally occur during the oestrous cycle were not altered by the presence of the device. At all stages of the cycle the intra-uterine-device-containing horn had a greater wet weight and a correspondingly higher content of cytosolic receptor than its contralateral control horn, the cellular concentration of cytosolic receptor being apparently maintained. However, the intra-uterine-device-containing horn had significantly lower cellular concentrations (i.e. per mg of DNA) of nuclear receptor, particularly at late dioestrus and pro-oestrus. Thus the treated horn showed a decreased translocation of receptor in response to increases in circulating oestrogens. Both horns contained equivalent amounts of an activating factor implicated in translocation and measured in vitro by binding of cytosol receptor to oligo(dT)-cellulose. The presence of an intra-uterine device neither altered the dissociation constants (Kd) of the nuclear and cytosolic oestrogen-receptor complexes nor the stability of the nuclear receptor complex in vitro. The decreased translocation cannot thus be directly attributed to changes in the physical properties of the receptor. This decrease may be responsible for the anti-fertility effect of the intra-uterine device (which affects only the treated horn of the bicornuate rat uterus), since implantation of the blastocyst requires correct concentrations of nuclear oestrogen receptor.

scholarly journals The nuclear oestrogen receptor in the female rat. Effects of oestradiol administration during the oestrous cycle on the uterus and contrasting effects of progesterone on the uterus and hypothalamus

1981 ◽  
Vol 198 (2) ◽  
pp. 385-389 ◽  
Author(s):  
S Thrower ◽  
L Lim
Keyword(s):  
Adult Female ◽  
Oestrogen Receptor ◽  
Oestrous Cycle ◽  
Ovariectomized Rats ◽  
Female Rat ◽  
Oestrogen Receptors ◽  
Adult Rat ◽  
Receptor Interactions ◽  
Neural Tissues

Oestradiol administration to immature or ovariectomized rats has been reported to increase the uterine content of long-term nuclear oestrogen receptors. However, in the intact adult female rat, oestradiol administration did not increase the concentration of long-term nuclear oestrogen receptors at all phases of the oestrous cycle. Progesterone administration to rats in late dioestrus did not affect the concentration of uterine nuclear oestrogen receptors 24 h later, although it did prevent the normal cyclic increase at pro-oestrus in the concentration of hypothalamic nuclear oestrogen receptors. Our results therefore show that in the intact adult rat, factors other than the concentration of progesterone or oestradiol determine the nuclear concentration of oestrogen receptors in the uterus. They also demonstrate differences between neural and non-neural tissues in the regulation of oestrogen-receptor interactions.

scholarly journals Unoccupied nuclear oestrogen receptors in the female rat hypothalamus. Increases on oestrogen administration

1980 ◽  
Vol 190 (3) ◽  
pp. 833-837 ◽  
Author(s):  
J O White ◽  
L Lim
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Female Rat ◽  
Oestrogen Receptors ◽  
Rat Hypothalamus ◽  
Active Elements

A major proportion of the hypothalamic nuclear oestrogen receptors were available for complexing with radioactive oestradiol in vitro at 4 degrees C and were apparently unoccupied . At 6 h after oestradiol administration the content of unoccupied nuclear receptors had increased 2.5-fold and represented 71% of the total nuclear receptor content. These results suggest that unoccupied receptors may be active elements in the ‘long-term’ receptor population of the hypothalamus. Androgenized females had lower contents of these receptors.

A HIGH-AFFINITY BINDING SITE FOR THE ANTIOESTROGENS, TAMOXIFEN AND CI 628, IN IMMATURE RAT UTERINE CYTOSOL WHICH IS DISTINCT FROM THE OESTROGEN RECEPTOR

1981 ◽  
Vol 91 (1) ◽  
pp. 155-161 ◽  
Author(s):  
L. C. MURPHY ◽  
R. L. SUTHERLAND
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Oestrogen Receptor ◽  
Dissociation Constants ◽  
Significant Proportion ◽  
Immature Rat ◽  
High Affinity ◽  
Saturable Binding ◽  
Receptor Sites

A high-affinity, saturable antioestrogen binding site, which does not bind oestradiol, has been reported to exist in a number of oestrogen target tissues but not in the immature rat uterus. This study reports the results of a more thorough search for this site in immature rat uterine cytosol. When concentrations of uterine cytoplasmic oestrogen receptor were selectively depleted by translocation of 90–95% of the cytoplasmic oestrogen receptor to the nucleus, saturation analysis studies revealed that the antioestrogens, tamoxifen and CI 628, were bound to high-affinity, saturable binding sites which were present at about 2·5 times the concentration of the residual oestrogen receptor sites. Oestradiol could only partially inhibit the binding of tritiated antioestrogens to their saturable binding sites in this material indicating that a significant proportion of these sites were distinct from the oestrogen receptor sites. This was confirmed in experiments where oestrogen receptor sites were saturated in vitro with oestradiol and high-affinity, saturable sites for CI 628 and tamoxifen were still present. The CI 628 and tamoxifen had high affinity for these sites with dissociation constants of 1·0–1·6 nmol/l. These specific antioestrogen binding sites were present at about 5% of the concentration of oestrogen receptors in normal immature rat uterine cytosol which probably explains their previous lack of detection in this material.

Two high affinity estrogen binding proteins of different specificity in the immature rat uterus cytosol

Steroids ◽  
1974 ◽  
Vol 24 (4) ◽  
pp. 437-449 ◽  
Author(s):  
Georges Michel ◽  
Ingrid Jung ◽  
Etienne-Emile Baulieu ◽  
Claude Aussel ◽  
José Uriel
Keyword(s):  
Binding Proteins ◽  
Rat Uterus ◽  
Immature Rat ◽  
High Affinity ◽  
Estrogen Binding

A possible role of clomiphene citrate in the control of pre-ovulatory LH surge during induction of ovulation

1985 ◽  
Vol 109 (1) ◽  
pp. 58-63 ◽  
Author(s):  
Naoki Terakawa ◽  
Ikuya Shimizu ◽  
Hirohisa Tsutsumi ◽  
Toshihiro Aono ◽  
Keishi Matsumoto
Keyword(s):  
Nuclear Receptor ◽  
Clomiphene Citrate ◽  
Ovariectomized Rats ◽  
Receptor Complex ◽  
Oestrogen Receptors ◽  
Lh Surge ◽  
Serum Lh ◽  
Lh Release

Abstract. A possible role of clomiphene citrate (clomiphene) in the control of ovulation in anovulatory women was investigated. Since a single ip administration of 5 μg oestradiol-17β (E2) to long-term ovariectomized rats did not induce LH surge, the following studies were designed to determine whether pretreatment with clomiphene followed by administration of E2 could induce LH surge in the ovariectomized rats. Changes in cytoplasmic and nuclear oestrogen receptors (ER) were also examined in the pituitaries of these animals. An ip injection of 200 μg clomiphene suppressed serum LH levels significantly for 72 h. The clomiphene injection rapidly caused an elevation of nuclear ER with a concomitant depletion of cytoplasmic ER level in the pituitary and the ER levels remained almost unchaged for 72 h. An administration of E2 12 or 24 h after the clomiphene injection had no significant effects on either the serum LH levels or the cytoplasmic and nuclear ER levels, compared with those induced by clomiphene alone. However, LH surge and the depletion of nuclear ER in the pituitary occurred 24 h later when E2 was injected 48 h after the clomiphene administration. The E2-induced LH release seems to be induced by a replacement of clomiphene by E2 on the nuclear receptor complex. These results suggest that clomiphene may exert actions directly on the pituitary gland to augment oestrogeninduced LH release.

scholarly journals High affinity binding of anti-oestrogen to the chick liver nuclear oestrogen receptor

1982 ◽  
Vol 206 (2) ◽  
pp. 387-394 ◽  
Author(s):  
Catherine B. Lazier ◽  
V. Craig Jordan
Keyword(s):  
Nuclear Receptor ◽  
Oestrogen Receptor ◽  
Potent Inhibitor ◽  
Inhibitory Effect ◽  
Affinity Binding ◽  
Soluble Receptor ◽  
High Affinity ◽  
Receptor Concentration ◽  
Liver Nuclei

Tamoxifen is a potent inhibitor of specific oestrogen-induced yolk protein synthesis by chicken liver. The oestradiol receptor in salt extracts of liver nuclei from oestrogen-treated chicks has a Kd for oestradiol of 0.7±0.2nm. Tamoxifen and its metabolite, monohydroxytamoxifen, compete for binding to the salt-soluble nuclear receptor with Ki values of 2.6 and 0.1nm respectively. The anti-oestrogens show much less inhibition of [3H]oestradiol binding when assays are carried out using intact nuclei. The competition by unlabelled oestradiol for [3H]oestradiol binding to receptor is identical in both salt extracts and intact nuclei. This suggests that intact nuclei contain components which bind anti-oestrogens, but not oestradiol. While tamoxifen and desmethyltamoxifen will readily dissociate from the salt-soluble nuclear oestrogen receptor, monohydroxytamoxifen does not dissociate under the conditions generally used for exchange assays. A modified assay was developed in which 60–70% of monohydroxytamoxifen-bound sites were shown to be exchangeable for [3H]oestradiol. Soluble receptor preparations were first incubated in a 1.7% charcoal suspension at 37°C for 15min before assay of specific oestradiol binding. This technique was used in examining the effects of tamoxifen and monohydroxytamoxifen given in vivo on the nuclear oestrogen receptor concentration. Despite their 30-fold difference in binding affinity for the receptor, both anti-oestrogens increase nuclear receptor levels to about the same degree. When given with oestradiol, both compounds have the same apparent partial inhibitory effect on the oestrogen-induced increase in nuclear receptor. These data are consistent with the metabolic hydroxylation of tamoxifen before binding to the hepatic oestrogen receptor.

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