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.

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 Developmental changes in the content of oestrogen receptors in the hypothalamus of the female rat

1979 ◽  
Vol 184 (2) ◽  
pp. 465-468 ◽  
Author(s):  
J O White ◽  
C Hall ◽  
L Lim
Keyword(s):  
Nuclear Receptors ◽  
Early Development ◽  
Nuclear Receptor ◽  
Sexual Differentiation ◽  
Fold Increase ◽  
Developmental Changes ◽  
Female Rat ◽  
Oestrogen Receptors

Hypothalamic cytosol and nuclear oestrogen receptors are present at birth. A 2-fold increase in cytoplasmic receptor content occurs by the second week, whereas the first significant and equivalent increase in nuclear receptor occurs in the fourth week. The latter reflects reported increases in oestradiol availability thought to lead to complete feminine sexual differentiation. The presence of nuclear receptors in the newborn suggests a requirement for oestrogenic stimulation in early development.

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.

scholarly journals Sequential changes in rat liver nuclear tri-iodothyronine receptors and mitochondrial α-glycerophosphate dehydrogenase activity after administeration of tri-iodothyronine

1979 ◽  
Vol 182 (2) ◽  
pp. 377-382 ◽  
Author(s):  
Hirotoshi Nakamura ◽  
Satoshi Hamada ◽  
Hiroo Imura
Keyword(s):  
Dehydrogenase Activity ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Rat Liver ◽  
Time Course ◽  
Delayed Response ◽  
Histone Proteins ◽  
Glycerophosphate Dehydrogenase ◽  
Receptor Concentration ◽  
Hormonal Modulation

The dynamics of the induction of nuclear tri-iodothyronine receptors and mitochondrial α-glycerophosphate dehydrogenase were studied in rat liver after a single injection of tri-iodothyronine. The maximal binding capacity (Cmax.) and association constant (Ka) of the nuclear receptors were determined by Scatchard analyses with and without correction for the endogenous tri-iodothyronine measured by radioimmunoassay. The administration of tri-iodothyronine induced sequential increases in the concentration of nuclear receptors and α-glycerophosphate dehydrogenase activity in the liver. The nuclear-receptor concentration was increased to 2.5 times that in the hypothyroid rat 1 day after the administration of hormone, and then decreased, with a half-life of about 2 days. α-Glycerophosphate dehydrogenase activity changed in parallel with the nuclear-receptor concentration, showing a delayed response. The total amount of non-histone protein in the liver was significantly increased 3 days after the administration. It seems likely therefore that the tri-iodothyronine-induced increase in nuclear-receptor concentration is responsible, at least in part, for the induction of this enzyme. The possibility is also suggested that nuclear receptors may be one of the non-histone proteins selectively synthesized at an early stage of the hormonal stimulation. Throughout the time course, the Ka values of the nuclear receptors for tri-iodothyronine remained unchanged, when corrected for endogenous tri-iodothyronine bound to the non-histone proteins, although they were apparently changed when the correction was not made. The results obtained provide further evidence for hormonal modulation of the nuclear receptors which is closely linked with the hormonal effect.

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 Unoccupied binding sites for oestrogen in nuclei of a breast tumour cell line (MCF-7)

1981 ◽  
Vol 200 (3) ◽  
pp. 515-520 ◽  
Author(s):  
A Geier ◽  
M Haimsohn ◽  
Z Malik ◽  
B Lunenfeld
Keyword(s):  
Nuclear Receptor ◽  
Fold Increase ◽  
Breast Tumour ◽  
Considerable Change ◽  
Tumour Cell Line ◽  
Nuclear Fraction ◽  
Oestrogen Receptors ◽  
Triton X ◽  
Mcf 7 ◽  
In Cells

1. A method to measure both occupied and unoccupied oestrogen receptors directly in the crude nuclear fraction of the MCF-7 cells was developed. The receptors had high affinity for oestradiol (Kd approx. 0.7 nM) and binding specificity characteristics of oestrogen receptors. 2. A substantial amount of the unoccupied receptors were found in the crude nuclear fraction. 3. Several experiments excluded the possibility that the unoccupied nuclear receptor might be a cytoplasmic contaminant. (a) Multiple extractions with Tris buffer released about 75% of the total receptor content, leaving the rest unextractable in the crude nuclear fraction. (b) Nuclei purified by centrifugation through 1.8M-sucrose and treatment with 0.7% Triton X-100, or by centrifugation through 50% glycerol with 0.1% Triton X-100 contained similar amounts of unoccupied receptors to that found in the crude nuclear fraction. (c) In cells cultured during 5 days after preconfluency a 3-fold increase in the amount of unoccupied cytoplasmic receptors occurred, whereas the amount of unoccupied nuclear receptors did not change significantly and conversely in cells exposed to increasing concentrations of oestradiol the unoccupied cytoplasmic receptor was continuously depleted but no considerable change in the unoccupied nuclear receptor was found.

scholarly journals Cyclic changes in the responsiveness of regressing corpora lutea to the luteolytic effects of prolactin in rats

Reproduction ◽  
2001 ◽  
pp. 411-417 ◽  
Author(s):  
F Gaytan ◽  
C Bellido ◽  
C Morales ◽  
JE Sanchez-Criado
Keyword(s):  
Corpus Luteum ◽  
Fold Increase ◽  
Oestrous Cycle ◽  
Corpora Lutea ◽  
Apoptotic Cells ◽  
Experimental Conditions ◽  
Lytic Effect ◽  
Steroidogenic Cells ◽  
Cyclic Changes ◽  
Apoptotic Effects

In cyclic rats, apoptosis of luteal cells during structural luteolysis occurs cyclically at the transition from pro-oestrus to oestrus in response to the preovulatory prolactin surge. This finding indicates that cyclic changes in apoptosis during luteolysis are dependent on prolactin surge cyclicity. In this study, the effects of prolactin on structural luteolysis were studied under different experimental conditions in relation to the phase of the oestrous cycle. In rats treated with prolactin at metoestrus and dioestrus, apoptosis did not occur in regressing corpora lutea, whereas in rats treated with prolactin on the morning of pro-oestrus, a 12.3-fold and 3.4-fold increase were observed in the number of apoptotic cells in regressing corpora lutea of the current and previous oestrous cycles, respectively. However, when the preovulatory prolactin surge and hence the subsequent apoptotic burst were blocked, prolactin treatment at the dioestrus phase induced a 13-fold increase in the number of apoptotic cells and significant changes in the volume of the corpus luteum (38% decrease) and the number of steroidogenic cells per corpus luteum (70% decrease). The results of this study indicate that the responsiveness of the regressing corpus luteum to the pro-apoptotic effects of prolactin are dependent on the phase of the oestrous cycle and on the presence or absence of an apoptotic burst in response to the preovulatory prolactin surge on the evening of pro-oestrus. Steroidogenic cells surviving to the apoptotic burst during the transition from pro-oestrus to oestrus became refractory to the lytic effect of prolactin. Furthermore, these cells also responded to the luteotrophic effects of prolactin, reaching full morphological luteinization, as indicated by the rescue of regressing cyclic corpora lutea during pregnancy.

Study of the role of histidyl, tyrosyl, α- or ε-amino residues in the specific binding of 3,5,3'-triiodothyronine to rat liver nuclear receptors

1988 ◽  
Vol 117 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Julius Brtko ◽  
Ján Knopp
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Rat Liver ◽  
Binding Capacity ◽  
Specific Binding ◽  
Biologically Active ◽  
Amino Groups ◽  
Trinitrobenzenesulfonic Acid ◽  
Receptor Molecule

Abstract. The role of histidyl, tyrosyl, α-or ε-amino residues of rat liver nuclear receptors for the specific binding of T3 was studied by chemically modifying the receptor molecule. The kinetics of the formation of N-carbethoxyhistidyl derivative from histidyl groups of nuclear receptors by diethylpyrocarbonate was examined. The modified nuclear receptor fraction was separated from diethylpyrocarbonate by gel filtration and the T3 binding parameters (Ka and MBC) at pH 8.0 were tested by Scatchard plot analysis. At 0.1 mmol/l diethylpyrocarbonate, the value of Ka was significantly (P < 0.01) decreased without any change in maximal binding capacity (MBC). The modification of α- or ε-amino groups of nuclear receptors by excess of trinitrobenzenesulfonic acid, 6.3 mmol/l at pH 8.5, resulted in a 4-fold increase in MBC of T3 specific binding without any change in Ka. In addition, acetylation of tyrosyl residues of nuclear receptors at pH 7.5 with an excess of 24 mmol/l N-acetylimidazole was performed. No changes in nuclear receptor Ka or MBC were observed after N-acetylimidazole treatment. Histidine and/or amino groups of the receptor molecule seem to hold a key position in the generation of the biologically active T3-nuclear receptor complex in the rat liver.

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 Changes in the concentration of high-affinity oestradiol receptors in rat uterine supernatant preparations during the oestrous cycle, pseudopregnancy, pregnancy, maturation and after ovariectomy

1970 ◽  
Vol 120 (4) ◽  
pp. 837-844 ◽  
Author(s):  
Patricia Feherty ◽  
D. M. Robertson ◽  
H. B. Waynforth ◽  
A. E. Kellie
Keyword(s):  
Early Pregnancy ◽  
Similar Pattern ◽  
Quantitative Method ◽  
Oestrous Cycle ◽  
High Concentration ◽  
Physiological Conditions ◽  
High Affinity ◽  
Receptor Sites ◽  
Receptor Concentration ◽  
Cyclic Changes

A quantitative method was used to determine the concentration of high-affinity oestradiol-receptor sites in rat uterine supernatant preparations under various physiological conditions. Cyclic changes in concentration were observed during the oestrous cycle, with a maximum occurring in late dioestrus. The changes followed a similar pattern in endometrium and myometrium, although concentrations were higher in the former. In pseudopregnancy the concentration was initially low, rising to a maximum on the tenth day. In early pregnancy a high concentration of receptor was found to be associated with the developing placenta, but this declined in later stages of pregnancy. After ovariectomy or combined ovariectomy and adrenalectomy the receptor concentration remained at a constant low value that could be increased by treatment with oestradiol. The receptor concentration was considerably higher in immature than in adult uteri.

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