PROGESTERONE-INDUCED OESTROGEN RECEPTORS IN THE RAT UTERUS

1978 ◽  
Vol 76 (1) ◽  
pp. 145-154 ◽  
Author(s):  
DOMINIQUE MARTEL ◽  
ALEXANDRE PSYCHOYOS

SUMMARY In ovariectomized rats progesterone acts like oestradiol at the endometrial, but not at the myometrial level, by increasing the number of oestrogen receptors in the cytoplasm. After 3 days of progesterone priming, the number of endometrial oestrogen receptors was found to be three times higher (P<0·05, Student's t-test) than control values. This progesterone-induced oestrogen receptor molecule appears identical in its physicochemical properties (sedimentation coefficient, kinetic constants, steroid specificity) to that induced in the endometrium and myometrium under the influence of oestradiol. However, in the myometrium progesterone acts antagonistically reducing significantly (P< 0·001, Student's t-test) the oestradiol-induced increase in the number of oestrogen receptors.

2006 ◽  
Vol 188 (2) ◽  
pp. 167-177 ◽  
Author(s):  
J E Sánchez-Criado ◽  
J Martín de las Mulas ◽  
C Bellido ◽  
V M Navarro ◽  
R Aguilar ◽  
...  

In the rat, oestrogen is a key regulator of gonadotrophin synthesis and release through activation of oestrogen receptors (ERs). Gonadotropes express α and β isoforms of ER and both can activate transcription in response to oestrogen. These experiments were aimed at evaluating the relative contribution of ERα and ERβ on gonadotrope morphology, progesterone receptor (PR) expression and LH secretion. Ovariectomized rats were daily injected over 3 days with 25 μg oestradiol benzoate, 0.3 or 1.5 mg of the selective ERα agonist propylpyrazole triol (PPT) with or without 1.5, 3.0 or 4.5 mg of the selective ERβ agonist diarylpropionitrile (DPN), DPN alone, and 0.3 or 3 mg of tamoxifen. Controls were given 0.2 ml oil. Serum concentration and pituitary content of LH, gonadotrope PR expression, pituitary PR content, and gonadotrope morphology were analyzed by RIA, immunohistochemistry, Western blotting and light and electron microscopy, respectively. Results showed that PPT reversed all consequences of ovariectomy, DPN mimicked the effects of PPT except for its LH-releasing action and tamoxifen had ERα-like responses. When combined with PPT, DPN attenuated ERα effects without interfering with its LH-releasing activity. Oestradiol benzoate had similar effects to those of combined PPT and DPN. It is suggested that (i) the structural reorganization of the cytoplasmic organelles provided by oestrogen, and the shrinkage of the ovariectomy-induced hypertrophy of gonadotropes, which precedes the expression of PR, are evoked by ERα and modulated, in a ying–yang fashion, by ERβ; and (ii) the oestrogen-dependent exocytosis of LH, the final step in the secretory process, is dependent on ERα exclusively.


1981 ◽  
Vol 194 (3) ◽  
pp. 667-671 ◽  
Author(s):  
S Thrower ◽  
C Neethling ◽  
J O White ◽  
L Lim

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.


1978 ◽  
Vol 78 (1) ◽  
pp. 71-81 ◽  
Author(s):  
V. C. JORDAN ◽  
LINDA ROWSBY ◽  
C. J. DIX ◽  
G. PRESTWICH

The dose-related effects of non-steroidal antioestrogens and oestrogens on the measurement of cytoplasmic oestrogen receptors in the rat uterus have been determined. The simultaneous administration of tamoxifen or monohydroxytamoxifen and oestradiol on three consecutive days resulted in dose-dependent decreases in both the wet weight of the uterus and the number of available cytoplasmic oestrogen receptors. The oestrogenic triphenylethylenes ICI 47 699 and ICI 3188 both produced dose-dependent decreases in the number of available cytoplasmic oestrogen receptors. Increasing doses of ICI 47 699 resulted in increasing concentrations of oestrogen receptors within the nucleus. The effects of tamoxifen and oestradiol-17β were compared in the ovariectomized mouse; replenishment of uterine oestrogen receptors was less evident in tamoxifen-treated animals than in animals receiving oestradiol, although increases in uterine weight were similar. A single large dose of tamoxifen (50 μg) produced a prolonged depletion of cytoplasmic oestrogen receptors whilst stimulating rises in uterine weight and DNA and protein content. The results demonstrate that the depletion of the uterine cytoplasmic oestrogen receptor pool is a function of the dose administered for any compound with the ability to translocate oestrogen receptors to the nucleus and as such is not an exclusive characteristic of non-steroidal antioestrogens.


1982 ◽  
Vol 208 (1) ◽  
pp. 199-204 ◽  
Author(s):  
J O White ◽  
P A Moore ◽  
W Marr ◽  
M G Elder ◽  
L Lim

Progesterone therapy results in partial reversibility of histological abnormalities of the rat uterus exposed to constant oestrogen stimulation and is associated with a decrease in nuclear oestrogen receptor content, which may underlie the tissue response to hormone treatment [White, Moore, Elder & Lim (1982) Biochem. J. 202, 535-41]. The synthetic progestins norgestrel and norethisterone used in this study were as effective as progesterone in decreasing the content of nuclear oestrogen receptor. However, only norgestrel had an ameliorative effect on epithelial hyperplasia and metaplasia. The non-steroidal anti-oestrogen tamoxifen caused a significant decrease in both nuclear and cytosol oestrogen receptor content without any change in luminal epithelial hyperplasia and metaplasia. Each progestin caused an increase, whereas tamoxifen caused a decrease, in the proportion of nuclear oestrogen receptors that were unoccupied. Each compound caused a decrease in the content of cytosol progesterone receptor. The effectiveness of compounds used as oestrogen antagonists is discussed with reference to their mode of action.


1981 ◽  
Vol 91 (2) ◽  
pp. 281-287 ◽  
Author(s):  
ANDREA MANNI ◽  
REBECCA BAKER ◽  
B. M. ARAFAH ◽  
O. H. PEARSON

The effect was studied of repeated injections of oestradiol-17β (5, 10, 25, 50 μg) given for various lengths of time (3, 5, 9 days) on total cell content of oestrogen receptors and cytosol progesterone receptors in the uteri of ovariectomized rats. An additional group of rats was injected daily with 50 μg oestradiol benzoate (OB) for 9 days in order to achieve a more sustained concentration of oestradiol in the blood. Injections were begun 24 h after ovariectomy and the rats were killed 24 h after the last injection. Daily administration of 5 μg oestradiol prevented the initial transient rise in oestrogen receptors which was observed in the uteri of untreated rats after ovariectomy. Repeated injections of 10 μg oestrogen produced an initial lowering in oestrogen receptors after 3 days of treatment which was followed by a prompt rise at 5 and 9 days when treatment was continued. A significant reduction in oestrogen receptors occurred at all times studied when rats were injected daily with 25 and 50 μg oestradiol. A more profound reduction in oestrogen receptors was observed in the group of rats treated for 9 days with 50 μg OB. Synthesis of progesterone receptors was stimulated by all doses of oestrogen studied. Concentrations of progesterone receptors were significantly higher after 3 and 5 days of treatment with 25 and 50 μg oestrogen. After 9 days of treatment, however, concentrations of progesterone receptors were virtually identical in all treated groups, including the group treated with OB. We have concluded that large doses of oestrogen significantly decrease oestrogen receptor content in the rat uterus, especially when OB is used. The degree of reduction, however, is only moderate under these experimental conditions and is insufficient to inhibit synthesis of progesterone receptors.


1981 ◽  
Vol 198 (2) ◽  
pp. 385-389 ◽  
Author(s):  
S Thrower ◽  
L Lim

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.


2018 ◽  
Vol 49 (2) ◽  
pp. 91
Author(s):  
N. G. KOSTOMITSOPOULOS (Ν.Γ. ΚΩΣΤΟΜΗΤΣΟΠΟΥΛΟΣ)

The oestrogen receptor is a ligand-activated transcription factor that modulates specific gene expression by binding to short DNA sequences. The study of the role of oestrogen receptor on the expression of the mitogenic actionof oestrogens and oncogenesis lead biomedical research in new approaches of the treatment of oestrogen-dependent tumors by using antioestrogens. Main mechanism of action of antioestrogens is the prevention of oestrogen action by blocking the binding of oestradiol to the oestrogen receptor. Tamoxifen, the most wellknown antioestrogen, is widely used as adjuvant therapy in all stages of human breast cancer. Recently interest is focused on the potential use of "pure" antioestrogens. The use of antioestrogens in veterinary oncology is also under discussion.


1978 ◽  
Vol 171 (1) ◽  
pp. 137-141 ◽  
Author(s):  
F Auricchio ◽  
A Rotondi ◽  
P Sampaolo ◽  
E Schiavone

1. An oestrogen receptor is present in low-salt cytosol of the mammary gland of lactating mice as a large aggregate; it is excluded from gel matrix when filtered on a Sephadex G-200 column and sediments at 7S in sucrose gradients. After incubation of cytosol with heparin, the receptor is dissociated. On a Sephadex G-200 column, it is included in the gel matrix and eluted as a protein with mol.wt. 260000 and a Stokes radius of 6.8nm; it sediments at 6S in sucrose gradients. 2. Dissociation of the mammary-gland cytosol oestrogen receptor seems to be the result of interaction of the oestrogen-receptor complex with heparin. This receptor interacts with heparin covalently bound to Sepharose, thereafter sedimenting at 6S. By using this interaction, the cytosol receptor was purified 200-fold compared with the homogenate, with a yield of 70%. 3. The cytosol receptor that was not incubated or was incubated with heparin was much smaller during sucrose-gradient centrifugation than during gel filtration. This discrepancy can be explained by pressure-induced dissociation during high-speed centrifugation. This possibility is supported by the decrease in the sedimentation coefficient of the receptor with increased duration of centrifugation.


1990 ◽  
Vol 20 (4) ◽  
pp. 779-783 ◽  
Author(s):  
J. A. Bearn ◽  
K. M. Fairhall ◽  
I. C. A. F. Robinson ◽  
S. L. Lightman ◽  
S. A. Checkley

SynopsisWe describe a novel neuroendocrine test which reflects a central response to activation of oestrogen receptors. This is achieved by measurement of plasma levels of oestrogen-stimulated neurophysin (ESN) following an oestrogen challenge. In normal women the ESN response to ethinyl oestradiol is dose-dependent. This response is attenuated in normal women during the first postpartum month, although it is unchanged in patients with anorexia nervosa, in spite of their similar concurrent hypo-estrogenic state. The altered puerperal response may result from the acute oestrogen withdrawal which occurs at delivery. The time course of the altered ESN response coincides with the period of maximum risk for puerperal psychosis. The ESN response to oestrogen provides a novel neuroendocrine measure to test the relevance of changes in central oestrogen receptor responsiveness in the pathogenesis of puerperal psychosis.


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