scholarly journals Intracellular relationships of the oestrogen receptor in the rat uterus and hypothalamus during the oestrous cycle

1978 ◽  
Vol 172 (1) ◽  
pp. 37-47 ◽  
Author(s):  
J O White ◽  
S Thrower ◽  
L Lim
Keyword(s):  
Oestrogen Receptor ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Nuclear Binding ◽  
Age Related ◽  
Wet Weight ◽  
Cyclic Changes ◽  
Nuclear Content

Simultaneous measurements were made of the specific oestrogen receptor in the nuclear and cytosol fractions prepared from the uterus and hypothalamus of 50–81-day-old female rats undergoing a 4-day oestrous cycle. In the uterus, the content of nuclear receptor fluctuated in concert with known cyclic changes in the secretion of oestrogen, being maximal at pro-oestrus. Over the period of 50–81 days, the nuclear content at all phases increased with age, again corresponding to known age-related increases in ovarian secretion of oestrogen. This age-related increase in nuclear content, averaged from the values of the different phases in each age group, was related to equivalent increases in uterine wet weight, an increase of 1 pmol of receptor being accompanied by an increase of 80–90 mg. The concentration of cytosol receptor was maintained constant, with respect to wet weight, throughout the cycle and with age, irrespective of changes in nuclear content. In the uterus of normal mature females, translocation of receptor into the nucleus did not lead to depletion of cytosol receptor, suggesting a process of continuous replenishment/synthesis. In the hypothalamus, the nuclear content of oestrogen receptor was also maximal at pro-oestrus. In contrast with the uterus, the content of hypothalamic cytosol receptor was minimal at this phase and reflects depletion of the cytosol receptor, possibly as a result of translocation. The extent of translocation was low compared with that in the uterus and did not alter with age during the age-period studied. This low nuclear binding of the receptor in vivo is discussed in relation to the presence of a cytosol factor, present in limiting amounts, which in vitro mediates the binding of cytosol receptor to oligo(dT)-cellulose. The difference in the physiological response of the uterus and of the hypothalamus to oestrogens may be related to the extent of nuclear binding of receptor.

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.

Effect of theophylline on nuclear retention of oestrogen-receptor complexes: correlation with oestrogen responses

1985 ◽  
Vol 105 (3) ◽  
pp. 397-403
Author(s):  
J. Steinsapir ◽  
A. M. Rojas ◽  
M. E. Bruzzone ◽  
A. White ◽  
O. Alarcón ◽  
...  
Keyword(s):  
Body Weight ◽  
Oestrogen Receptor ◽  
Nuclear Retention ◽  
Adult Rat ◽  
Receptor Complexes ◽  
Wet Weight

ABSTRACT In the ovariectomized adult rat uterine oedema induced by 0·01 and 0·1 μg oestradiol-17β/100 g body weight increased further in the presence of theophylline. Nuclear retention of oestrogen-receptor complexes also increased in response to theophylline both in vivo and in vitro. Theophylline decreased the number of eosinophils in the blood and concurrently decreased oestrogen-induced uterine eosinophilia at doses of 0·001, 0·01, 0·1, 1, 10 or 30 μg oestradiol/100 g body weight, through a mechanism independent of glucocorticoids. There was, therefore, no correlation between changes in the number of uterine eosinophils and changes in uterine wet weight induced by theophylline and oestrogen. It is suggested that the presence of oestrogen-receptor complexes in the nucleus for at least 4 h is a prerequisite for the induction of uterine oedema and growth in the presence of theophylline and oestradiol-17β. J. Endocr. (1985) 105, 397–403

IN VITRO UPTAKE OF TRITIATED OESTRADIOL BY THE RAT ANTERIOR HYPOTHALAMUS DURING THE OESTROUS CYCLE

1970 ◽  
Vol 63 (4) ◽  
pp. 577-584 ◽  
Author(s):  
Junzo Kato
Keyword(s):  
Posterior Hypothalamus ◽  
Anterior Hypothalamus ◽  
Oestrous Cycle ◽  
Physiological Regulation ◽  
Cortex Cerebri ◽  
Anterior Hypophysis ◽  
Cyclic Changes ◽  
In Vitro Uptake

ABSTRACT The anterior, middle and posterior hypothalamus, the cortex cerebri, the anterior hypophysis, and the diaphragm of postpubertal rats at different phases of the oestrous cycle were incubated in vitro with tritiated 17β-oestradiol. Uptake of radioactivity by the anterior hypothalamus at prooestrus and oestrus was lower than that at dioestrus. In contrast no fluctuation in the concentration of the radioactivity in the other parts of brain, the hypophysis and muscle was observed during the oestrous cycle. These in vitro findings are consistent with the in vivo observations of cyclic changes in phase with the oestrous cycle of the amount of radioactive oestradiol taken up by the anterior hypothalamus following the injection of tritiated oestradiol (Kato et al. 1969b). Thus it is further suggested that the oestradiol receptor in the anterior hypothalamus of the rat is involved in the physiological regulation and maintenance of cyclic changes in the hypothalamo-pituitary system through the mechanism of action of feedback of oestrogen.

scholarly journals Dynamics of oestrogen-receptor distribution between the cytosol and nuclear fractions of immature rat uterus after oestradiol administration

1975 ◽  
Vol 146 (3) ◽  
pp. 617-623 ◽  
Author(s):  
J Mešter ◽  
E E Baulieu
Keyword(s):  
Oestrogen Receptor ◽  
Binding Capacity ◽  
Residual Fraction ◽  
Initial Value ◽  
Cytosol Fraction ◽  
Initial Concentration ◽  
Nuclear Binding ◽  
Receptor Concentration

1. The nuclear-myofibrilar (800g pellet) fraction of the uterus from immature (22-23 days old) rats not exposed to oestrogen exhibits saturable binding of oestradiol. The nuclear binding capacity represents approximately 10% of that of the cytosol fraction (approx. 3.5 fmol/mug of DNA). The predominant part (0.3.5 fmol/mug of DNA) of the nuclear binind sites are present in the residual pellet after extraction with 0.5 M-KC1. 2. By using an exchange technique in vitro, determinations of the nuclear binding sites have been carried out after administration of 1 mug of oestradiol in vivo. Within 0.5h after the hormone injection, the concentration of nuclear bindng sites increased to approx. 0.4 fmol/mug of DNA in the 0.5 M-KC1-extractable fraction, and to approx. 1.2 fmol/mug of DNA in the residual fraction. Meanwhile the cytosol oestrogen-receptor concentration decreased to approx. 10% of its initial value. In the following period from 0.5 h after the oestradiol injection onwards, the concentration of nuclear oestrogen receptors decreased with halflife values of approx. 140 and 200 min for the KC1(0.5 M)-extractable and residual form respectively. At the same time, the cytosol receptor concentration increased to reach approx. 50% of the initial value by the 6h. This increase could not be blocked by cycloheximide. The initial concentration of cytosol receptor was restored approx. 11h after the injection and the increase during the 6-11h period was sensitive to cycloheximide inhibition, suggesting protein-synthesis-dependence of the process. 3. With the (more) physiological dose of oestradiol (0.1 mug), the decrease the cytosol receptor was only 50% by 4h and this was followed by a period (up to 12h after injection) during which the initial concentration was restored. During this period the increase of the receptor can be blocked by cycloheximide.

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 Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 1985
Author(s):  
Xiaohe Li ◽  
Ling Ma ◽  
Kai Huang ◽  
Yuli Wei ◽  
Shida Long ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
In Vivo Experiments ◽  
Age Related ◽  
And Migration ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.

scholarly journals Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo
Keyword(s):  
Oxidative Stress ◽  
Food Sources ◽  
Preventive Action ◽  
Nutritional Interventions ◽  
Beneficial Effects ◽  
Age Related ◽  
Macromolecular Damage ◽  
And Oxidative Stress

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

scholarly journals Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donita L. Garland ◽  
Eric A. Pierce ◽  
Rosario Fernandez-Godino
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Deposit Formation ◽  
Genetic Ablation ◽  
Age Related ◽  
Complement Dysregulation

AbstractThe complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.

scholarly journals Phytochemical Study and In Vitro Screening Focusing on the Anti-Aging Features of Various Plants of the Greek Flora

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1206
Author(s):  
Aimilia D. Sklirou ◽  
Maria T. Angelopoulou ◽  
Aikaterini Argyropoulou ◽  
Eliza Chaita ◽  
Vasiliki Ioanna Boka ◽  
...  
Keyword(s):  
Plant Species ◽  
High Performance ◽  
High Resolution Mass Spectrometry ◽  
Ultra Performance Liquid Chromatography ◽  
Skin Aging ◽  
Rosa Damascena ◽  
Phytochemical Study ◽  
Age Related

Skin health is heavily affected by ultraviolet irradiation from the sun. In addition, senile skin is characterized by major changes in the collagen, elastin and in the hyaluronan content. Natural products (NPs) have been shown to delay cellular senescence or in vivo aging by regulating age-related signaling pathways. Moreover, NPs are a preferable source of photoprotective agents and have been proven to be useful against the undesirable skin hyperpigmentation. Greek flora harvests great plant diversity with approximately 6000 plant species, as it has a wealth of NPs. Here, we report an extensive screening among hundreds of plant species. More than 440 plant species and subspecies were selected and evaluated. The extracts were screened for their antioxidant and anti-melanogenic properties, while the most promising were further subjected to various in vitro and cell-based assays related to skin aging. In parallel, their chemical profile was analyzed with High-Performance Thin-Layer Chromatography (HPTLC) and/or Ultra-Performance Liquid Chromatography High-Resolution Mass Spectrometry (UPLC-HRMS). A variety of extracts were identified that can be of great value for the cosmetic industry, since they combine antioxidant, photoprotective, anti-melanogenic and anti-aging properties. In particular, the methanolic extracts of Sideritis scardica and Rosa damascena could be worthy of further attention, since they showed interesting chemical profiles and promising properties against specific targets involved in skin aging.

Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release

1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Gonadal Hormone ◽  
Base Line ◽  
Pituitary Cells ◽  
Intact Male ◽  
Castrate Male ◽  
Basal Release

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

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