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Biomedical subjects

B L Nguyen

Publications and source records attributed to B L Nguyen.

At least 37 records · Page 2Linked to original sources
PubMed1991

Interaction of nitric oxide and cGMP with signal transduction in activated platelets.

Although nitric oxide (NO), one of the endothelium-derived relaxing factors, prevents formation of platelet aggregates, the mechanism by which this occurs is not fully understood. Accordingly, the effect of NO on signal transduction of gel-filtered human platelets was measured and compared with that of a cell-permeant guanosine 3',5'-cyclic monophosphate (cGMP) analogue, 8-bromo-cGMP (8-BrcGMP). NO inhibited the rise in intracellular Ca2+ concentration ([Ca2+]i), phosphorylation of the 47-kDa substrate (p47) of protein kinase C (PKC), serotonin secretion, and phosphatidic acid production induced by thrombin or the endoperoxide analogue U-46619. Similar effects were seen with 8-BrcGMP, and NO induced a concentration-related rise in cGMP. Neither NO nor 8-BrcGMP inhibited platelet aggregation, [Ca2+]i mobilization, or serotonin secretion induced by the Ca2+ ionophores A23187 or ionomycin or directly activated PKC purified from platelets. However, both NO and 8-BrcGMP enhanced p47 phosphorylation induced by the Ca2+ ionophores without augmenting phosphatidic acid production. Thus, if [Ca2+]i is elevated, a rise in cGMP enhances PKC activation. Both NO and 8-BrcGMP, however, prevent Ca2+ mobilization and platelet aggregation induced by receptor-mediated agonists by interfering with signal transduction at a point proximal to phospholipase C activation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1990

Autoradiographic localization of [3H]oestradiol in epididymis, seminal vesicles and prostate of the fetal guinea-pig.

The selective uptake and localization of radioactivity in the fetal male reproductive organs (epididymis, seminal vesicles and prostate) of the guinea-pig (50-60 days of gestation) after in-vivo and in-situ subcutaneous injection of [3H]oestradiol was investigated by autoradiography. In 50-day-old fetuses, the different areas of the epididymis showed selective retention of radioactivity in the nuclei of peritubular and stromal cells surrounding the epididymal duct; no retention was observed in the epididymal epithelium. A similar distribution of silver grains was observed in the 60-day-old fetus. Seminal vesicles and prostate sections from both 50- and 60-day-old fetuses showed concentration and retention of radioactivity only in stromal cells, whereas the epithelium did not exhibit silver grains. In all the tissues studied, the nuclear labelling was abolished after injection of [3H]oestradiol plus a 100-fold excess of non-labelled oestradiol. As the mesenchyme surrounding the epithelia of the epididymis, seminal vesicles and prostate were labelled selectively with [3H]oestradiol, it is suggested that during fetal life of the guinea-pig the mesenchymal stroma of these fetal male reproductive organs may be considered as a target tissue for oestrogen.

Animals↗
PubMed1990

Metabolism and biologic response of estrogen sulfates in hormone-dependent and hormone-independent mammary cancer cell lines. Effect of antiestrogens.

Different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, and estriol-3-sulfate) can provoke important biologic responses in different mammary cancer cell lines; there is a significant increase in progesterone receptor. However, no significant effect was observed with estrogen-17-sulfates. The reason for the biologic response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines. [3H]-Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, and T47D), but very little or no conversion was found in hormone-independent mammary cancer cell lines (MDA-MB-231 and MDA-MB-436). Different antiestrogens (tamoxifen and its derivatives) and another potent antiestrogen, ICI 164,384, significantly decrease the concentration of estradiol after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect in the uptake and conversion of estrone sulfate was observed in hormone-independent mammary cancer cell lines. The data indicate that sulfatase activity for estrone sulfate is very low in the hormone-independent cell lines; however, comparative kinetic studies carried out after homogenization of MCF-7 and MDA-MB-436 cells show that sulfatase activity is similar, suggesting different mechanisms in the hydrolysis of estrone sulfate in hormone-dependent and hormone-independent cell lines. Progesterone also provokes a significant decrease in uptake and in estradiol levels after incubation of [3H]-estrone sulfate with the MCF-7 cell line. It is concluded that estrogen sulfates can play an important role in the biologic response of estrogens in breast cancer and that control of sulfatase and 17-hydroxysteroid dehydrogenase activities are key steps in the concentration and ability of estradiol in the mammary cancer cell line.

Breast Neoplasms↗
PubMed1989

Importance of estrogen sulfates in breast cancer.

Estrogen sulfates are quantitatively the most important form of circulating estrogens during the menstrual cycle and in the post-menopausal period. Huge quantities of estrone sulfate and estradiol sulfate are found in the breast tissues of patients with mammary carcinoma. It has been demonstrated that different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, estriol-3-sulfate) can provoke important biological responses in different mammary cancer cell lines: there is a significant increase in progesterone receptor. On the other hand, no significant effect was observed with estrogen-17-sulfates. The reason for the biological response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines. [3H]Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, T-47D), but very little or no conversion was found in the hormone-independent mammary cancer cell lines (MDA-MB-231, MDA-MB-436). Different anti-estrogens (tamoxifen and derivatives) and another potent anti-estrogen: ICI 164,384, decrease the concentration of estradiol very significantly after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect was observed for the uptake and conversion of estrone sulfate in the hormone-independent mammary cancer cell lines. Progesterone provokes an important decrease in the uptake and in estradiol levels after incubation of [3H]estrone sulfate with the MCF-7 cells. It is concluded that in breast cancer: (1) Estrogen sulfates can play an important role in the biological response of estrogens; (2) Anti-estrogens and progesterone significantly decrease the uptake and estradiol levels in hormone-dependent mammary cancer cell lines; (3) The control of the sulfatase and 17 beta-hydroxysteroid dehydrogenase activities, which are key steps in the formation of estradiol in the breast, can open new possibilities in the treatment of hormone-dependent mammary cancer.

Breast Neoplasms↗
PubMed1988

Effect of estradiol on the progesterone receptor and on morphological ultrastructures in the fetal and newborn uterus and ovary of the rat.

The effect provoked by estradiol after administration to pregnant rats (1 mg per day) was studied in fetal and newborn uteri and ovary. Estrogen receptors are found in the fetuses of non-treated animals. Their number (in fmol/mg DNA, +/- SD) in the fetal uterus (total sites, cytosol + nuclei) was at the age of 18 days: 63 +/- 15; at 20 days 101 +/- 13; and in the 24-h-old newborn; 415 +/- 120. The respective values in the ovary were: 105 +/- 25; 520 +/- 60 and 410 +/- 190. Estradiol stimulated significantly the progesterone receptor in the fetal uterus at 20 days old. The progesterone receptor (in fmol/mg DNA, +/- SD) which was 97 +/- 17 in the non-treated animals, increased to 790 +/- 90 in the E2-primed animals. Newborns, 24-h-old, had no detectable progesterone receptor, but in the E2-treated animals the value increased to 1210 +/- 120. In the fetal ovary of non-treated animals, progesterone receptor at the age of 18 days is: 90 +/- 19; at 20 days 132 +/- 47, and in the newborns 260 +/- 67; in the E2-treated animals, the values are respectively 330 +/- 49; 865 +/- 78 and 1280 +/- 307. In the fetal uteri of E2-treated animals, histological and ultrastructural studies showed an increase in the size of the uterine horn, the height of the epithelial cells, and stromal cell differentiation. It is suggested that, as was extensively demonstrated in the fetal compartment of the guinea-pig, the machinery for estrogen responses operates also during fetal development of the rat.

Animals↗
PubMed1988

Biological effects and ultrastructural alterations of cis-tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen in the uterus and vagina of newborn guinea pigs.

The biological and morphological effects of cis-tamoxifen, N-desmethyltamoxifen and 4-hydroxy-tamoxifen, administered sc alone (100 micrograms/animal) or combined with estradiol (20 micrograms/animal) were studied in the uterus and vagina of the guinea pig. After 2 days treatment the values of the uterine wet weights (mg +/- SD of 6-10 animals in each study) were as follows: non-treated animals (control): 142 +/- 15; animals treated with cis-tamoxifen: 119 +/- 4; N-desmethyltamoxifen: 280 +/- 20; 4-hydroxytamoxifen: 268 +/- 25. The values after long treatment were: 177 +/- 30; 490 +/- 65; 394 +/- 36 and 581 +/- 60, respectively. After short treatment the weights of the vaginas were: control: 99 +/- 20; cis-Tamoxifen: 67 +/- 2; N-desmethyltamoxifen: 153 +/- 25; 4-hydroxytamoxifen: 166 +/- 7; and after the long treatment: 155 +/- 40; 660 +/- 41; 467 +/- 38 and 502 +/- 61, respectively. N-desmethyltamoxifen and 4-hydroxytamoxifen increased the progesterone receptors in the uterus after short treatment (P less than 0.01) but not after 12 days treatment. On the other hand, there was no effect on progesterone receptor in the vagina after the short treatment but a very stimulatory effect after the long treatment. The morphological alterations after 12-days treatment indicate that the three tamoxifen derivatives in the two tissues studied provoke intense alterations in different organelles. In conclusion, it is suggested that the tamoxifen derivatives can act as real agonists in the uterus and vagina of the newborn guinea pig, and they do not block the effect provoked by estradiol.

Animals↗
PubMed1987

The complexity of anti-estrogen responses.

The actions and biological responses of anti-estrogens are a function of: the experimental conditions, the parameters, the organ and the animal species considered. Target tissues for estrogens in the guinea-pig during the perinatal period are interesting models to explore the action of anti-estrogens. The summary of the data indicates: (1) In the fetal uterus of guinea-pig in in vivo experiments (after injection to the maternal compartment) tamoxifen acts as a real agonist concerning growth, as a partial agonist concerning the stimulation of the progesterone receptor. (2) In in vitro experiments (in organ culture of fetal uterus or in isolated cells) anti-estrogens (tamoxifen or 4-hydroxy-tamoxifen) act as antagonists and also inhibit the effects provoked by estrogens. (3) In the uterus and vagina of newborn guinea-pigs, tamoxifen and its derivatives: 4-hydroxytamoxifen and N-desmethyltamoxifen act as real agonists concerning the uterotrophic and vaginotrophic effects, and also stimulate the amount of DNA per organ, but concerning the progesterone receptor in the uterus, in the short treatment anti-estrogens act as partial agonists but they have no effect in the long treatment. In the vagina in the short treatment anti-estrogens provoke no significant effects, but in the long treatment they are full agonists. In neither of the two biological responses studied (growth and progesterone receptor) does tamoxifen and its derivatives block the action of estradiol. (4) The use of a monoclonal antibody to the estrogen receptor revealed quantitative differences in the activation of the estrogen receptor when bound to estradiol or tamoxifen. This observation was in agreement with the lesser extent of binding to DNA-cellulose of the tamoxifen-estrogen receptor complex as compared with the estradiol-estrogen receptor complex. This fact suggests an impaired activation of the estrogen receptor induced by tamoxifen which might be related to the different biological responses provoked by estrogens and anti-estrogens.

Animals↗
PubMed1986

Biological responses of tamoxifen in the fetal and newborn vagina and uterus of the guinea-pig and in the R-27 mammary cancer cell line.

The biological and morphological responses of tamoxifen were studied in two models: the uterus and vagina of fetal and newborn guinea-pigs: R-27 cells--a mammary cancer cell line (tamoxifen resistant) derived from the MCF-7 cancer cell line. Tamoxifen (TAM) alone or in combination with estradiol (E2) was administered to pregnant (50-52 days of gestation) or to newborn (2-day-old) guinea-pigs for a long period (12 days). TAM alone produced a great trophic effect on the uterus and vagina which was markedly enhanced when TAM was administered together with E2. Histological studies showed that TAM provokes morphological changes in both the endometria and the myometria and this effect was also greater when TAM was administered together with E2. In the fetal uterus and vagina, the ultrastructural studies showed that TAM induces morphological alterations in different cytoplasmic organelles. This effect was much more intense in newborns where TAM provoked a significant vacuolization of the epithelial cells. Concerning progesterone receptor (PR) in the fetal or newborn tissues (uterus or vagina) TAM provoked a less intense effect than those provoked by E2, but TAM did not block the effect provoked by E2. It was observed that [3H]TAM binds specifically to the estrogen receptor (ER) of fetal guinea pig uterus and this complex is partially recognized by a monoclonal antibody which recognizes the activated form of this receptor, supporting the suggestion that the biological action of TAM is mediated by the ER. The biological and ultrastructural effects provoked by TAM (1 X 10(-6) M), estriol (E3)(5 X 10(-8) M) and the combination of TAM + E3 were studied in the R-27 mammary cancer cell line in culture. E3 stimulated the PR content by 7-10 times. However, TAM did not provoke a significant decrease in the concentration of PR, and in the mixture of TAM + E3 the concentration of PR was of the same order as that in E3 treatment. Ultrastructural observations indicate an intense concentration of ribosomes in the pericytoplasmic area after exposure to E3 and with exposure to TAM an increase in vacuoles and a significant enlargement of the size of the mitochondria were observed. It is concluded that TAM in the target tissues of fetal and newborn guinea pigs acts as a real estrogen and in the R-27 mammary cancer cell line TAM does not block the effect provoked by E3, however it does provoke intense ultrastructural modifications.

Animals↗
PubMed1986

Tamoxifen and progesterone effects in target tissues during the perinatal period.

The biological effects of tamoxifen (TAM), progesterone (P), or a combination of TAM + P were investigated in the uterus and vagina of newborn guinea pigs after short (2 days) and long (12 days) treatments. In both tissues, tamoxifen provoked a significant trophic effect which is indicated by the increase in weight, protein and DNA content. In the uterus, progesterone also provoked an increase in weight, protein and DNA content, but much less than that provoked by tamoxifen. In contrast, in the vagina progesterone had no effect on the weight, protein and DNA content, but progesterone did not block the agonistic effect provoked by tamoxifen. The situation was different when progesterone receptor was concerned. Tamoxifen in both tissues (particularly in the vagina) stimulated the progesterone receptor very significantly. Progesterone blocked the number of specific binding sites of progesterone and the stimulatory effect provoked by tamoxifen.

Animals↗
PubMed1986

Estrogen and progesterone receptors in the fetal and newborn vagina of guinea pig: biological, morphological, and ultrastructural responses to tamoxifen and estradiol.

Estrogen and progesterone receptors were characterized in the fetal and newborn vagina of guinea pig. The concentrations of estrogen receptor (total sites, cytosol plus nuclei) which were very high [7090 +/- 1700 (+/- SD) fmol/mg DNA] in the fetal vagina (62-64 days gestation) decreased significantly after birth and increased slightly at 2 weeks of age. Tamoxifen (TAM) and estradiol (E2) or the combined treatment (TAM + E2) induced a great increase in weight and DNA content in both the fetal and newborn vagina. After a 12-day treatment to pregnant or newborn guinea pigs, the fetal vagina wet weights (milligrams +/- SD) were as follows: control animals, 87 +/- 14; +TAM, 254 +/- 38; +E2, 177 +/- 19; +(TAM+E2), 218 +/- 41. The values in newborn vaginas were: 155 +/- 40, 434 +/- 75, 477 +/- 49, and 512 +/- 76, respectively. The DNA contents per vagina (in micrograms per +/- SD) in the fetal tissues were as follows: control, 187 +/- 64; +TAM, 563 +/- 74; +E2, 650 +/- 100; and +(TAM+E2), 776 +/- 113; in the newborn vagina these values were: 592 +/- 75, 880 +/- 113; 781 +/- 75, and 901 +/- 15, respectively. Histological studies showed drastic morphological alterations after each of the treatments, particularly in the epithelial cells. Similarly, the ultrastructural examination with transmission electron microscopy showed the alteration of mitochondria, the development of the rough endoplasmic reticulum, and the formation of numerous vacuoles and secretory granules. TAM stimulated the number of specific sites for progesterone, but less intensely than did E2. However, in the combined experiment (TAM+E2), TAM did not block the action of E2. It is concluded that TAM acts in the fetal and newborn vagina of guinea pigs as a real estrogen agonist.

Animals↗
PubMed1986

Oestrogen agonistic effects of tamoxifen in the uterus of newborn guinea pigs after short and long treatment. Biological and histological studies.

Tamoxifen (TAM) alone or combined with oestradiol (E2) or progesterone (P) was administered to newborn guinea pigs (2 days old) for short (2 days) or a long (12 days) treatment period. TAM alone provoked a great stimulatory effect on uterine growth and DNA content and the effect was particularly intense after the long treatment. These actions were markedly enhanced when TAM was administered together with E2. Following short treatment, the values of the uterine wet weights (mg +/- SD) were as follows: control animals, 142 +/- 15; animals treated with TAM, 298 +/- 53; E2, 335 +/- 15; (TAM + E2), 362 +/- 16. The values after the long treatment were 177 +/- 30, 555 +/- 93, 709 +/- 117 and 1263 +/- 222, respectively. Histological studies showed that TAM provoked morphological changes in both the endometrium and the myometrium. The effects were particularly great on the height of the luminal epithelial cells and on the uterine glands. After 2 days of treatment with E2, TAM and P, the thickness of the luminal epithelium, which was 13.5 micron +/- 1.5 in the control animals, increased as follows: TAM, 19 microns +/- 1.7; E2, 20.3 microns +/- 3.3; (TAM + E2), 30.5 microns +/- 5; P, 12 microns +/- 0.9 and (P + TAM), 19.7 microns +/- 1.2. The values after the 12 day treatment were: controls, 20.8 microns +/- 1.8; TAM, 27.4 microns +/- 2.1; E2, 32 +/- 3; (TAM + E2), 43 microns +/- 5; P, 17.8 microns +/- 1.2 and (P + TAM), 23.6 microns +/- 1.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

[Effect of tamoxifen and estrogens on breast cancer cell lines: MCF-7 and R-27, and on the uterus and vagina of fetal and newborn guinea-pigs].

The action of tamoxifen was studied in two models: in breast cancer cell lines MCF-7 and R-27. The latter is resistant to tamoxifen; 2) in the uterus and vagina of guinea pig during the perinatal period. In the breast cancer cell line MCF-7 tamoxifen blocks the proliferation of the cells and in the R-27 it does not antagonize the effects provoked by estrogens. However, in this cell line tamoxifen provokes a significant alteration of the ultrastructures. In the uterus and vagina of guinea pig (fetal and newborn) tamoxifen acts as a real estrogen and it does not block the effects provoked by estrogens.

Animals↗
PubMed1984

Biological responses and histological studies of estriol and estriol sulfate in fetal and newborn uteri of guinea pig.

The biological responses of estriol (E3) and of estriol-3-sulfate (E3-S) in the fetal and newborn uteri of guinea pig were studied. After a treatment of E3 (1 mg/kg/day) or E3-S (1.4 mg/kg/day) to pregnant guinea pigs (49-60 days of gestation) for 6 days, both estrogens provoke a significant uterotrophic effect in the fetal uterus which increases in weight 1.8-2.5 times in relation to the non-treated animals. The stimulation of progesterone receptor (PR) is also very intense, 7-12 times in relation to the control animals. In another series of experiments newborn guinea pigs (2-day old) were treated with 100 micrograms/animal of E3 or 140 micrograms/animal of E3-S for a short (2 days) or a long (12 days) period. Concerning the uterotrophic effect, the weight of the uterus increases 1.8-2.5 times (in relation to the non-treated animals) after a 2-day treatment and the effect continues to increase up to 4-5 times in the 12-day treated animals. In opposition to the fetal uterus, the effect on PR provoked by E3 or E3-S is very limited (only an increase of 1 time in relation to the non-treated animals); the effect is even less intense after the 12-day treatment. Histological studies show an intense hypertrophic effect particularly in the epithelium of the endometrium in the fetal and newborn uteri for both E3 and E3-S. In the newborns the effect is also intense on the epithelium of the uterine gland. It is concluded that: (1) Estriol and estriol sulfate are very active and with similar intensity on the uterine weight before and after birth; (2) The stimulatory effect on PR decreases very significantly after birth and after a long treatment; (3) E3-S can act as a potent hormonal precursor.

Animals↗
PubMed1983

Uptake, receptor and biological response of estrone in the fetal uterus of guinea pig.

In vivo and in situ subcutaneous injection of 30 muCi of 3H-estrone (3H-E1) to guinea pig fetuses was carried out to study the dynamics of the selective uptake and retention of this estrogen in the uterus and other fetal organs. In the fetal uterus an increase in the uptake of radioactivity with time was found which was maximal 1 h after injection of 3H-E1. The analysis of radioactive material showed that in the fetal uterus unmetabolized 3H-E1 accounts for 65-75% of the total radioactivity between 10 and 60 min after the injection and its maximal concentration is 2.5-15 times and 10 times higher than the maximal concentrations found in other fetal organs and fetal plasma, respectively. Significant amounts of 3H-E1 were also present in lung (33-60% of the total radioactivity in this tissue), brain (37-52%) and ovary (18-47%), while an important conversion of 3H-E1 into 3H-estradiol was observed in the kidney (20-26%). Estrogen sulfates, essentially estrone sulfate, represented the greater part of the fetal plasma radioactivity (30-49%). 3H-E1-specific binding sites in the cytosol of the fetal uterus were found with physicochemical characteristics (specifically limited to natural and synthetic estrogens, Kd = 8.1 +/- 1.2 x 10(-10) M (SD), sedimentation coefficient 8S) similar to those of the typical estrogen receptor. The cytosol receptor-3H-E1 complex has a dissociation rate constant (K-1) of 16 +/- 0.7 x 10(-4) s-1 at 25 degrees C. The responsiveness of the fetal uterus to estrone treatment was studied after subcutaneous administration of estrone to pregnant guinea pigs (1 mg/kg/day for 3 consecutive days). Two biological responses were observed: an increase in fetal uterine weight (50-100% in relation to the nontreated animals) and a significant stimulation of progesterone receptor protein (10-16 times higher than in control animals). At the same time, there was a 50-70% decrease in the total estrogen receptor concentration. It is concluded that estrone could be involved in the biological responses to estrogen in the fetal uterus of guinea pig.

Animals↗
PubMed1982

Effects of seven different oestrogen sulphates on uterine growth and on progesterone receptor in the foetal uterus of guinea pig after administration to the mother.

The biological effect of seven different oestrogen sulphates: oestrone-3-sulphate (E1-3-S), oestradiol-3-sulphate (E2-3-S), oestradiol-17-S), oestradiol-3,17-disulphate (E2 3,17-DS), oestriol-3-sulphate E3-3-S), oestriol-17-sulphate (E3-17-S), oestriol-3,16,17-trisulphate (E3-3,16,17-TS), was studied in the foetal uterus of guinea pig (55--65 days of gestation) after sc administration for 3 consecutive days of each sulphate to the mother. On day 4, two response parameters were investigated, the uterotrophic effect and the action on the progesterone receptor. The monosulphates at the C3 position of the oestrogens (E1-3-S, E2-3-S and E3-3-S) provoked an increase in uterine weight of 1.9--2.4 times in relation to the non-treated animals. These oestrogen sulphates also very significantly stimulated the number of progesterone specific binding sites, 7--10 times in relation to the non-treated animals. On the other hand, when the sulphate was at C17 of the oestrogens (E2-17-S, E3-17-S, E2-3-17-DS, E3-3,16,17-TS), very little or no effect on the foetal uterus was observed on the two parameters studied. It is concluded that oestrogen (oestrone, oestradiol, oestriol) sulphates in position C3 can be involved in the biological response to the hormone and it is suggested that the effect is carried out after the hydrolysis of the sulphate. On the other hand, sulphates in C17 are not hydrolysed and no significant biological effects were observed in the uterine growth or in the progesterone receptor.

Animals↗
PubMed1980

Receptor and biological response to estriol in the fetal uterus of guinea pig.

The binding of 3H-estriol was examined in the fetal uterus of guinea pig. The physico-chemical characteristics of the binding of 3H-estriol to macromolecules are similar to the typical receptor protein for estrogens. Different estrogens (estriol, estradiol, estrone and diethylstilbestrol) compete with this binding but progesterone and testosterone have no effect. The binding affinity has a Kd of 5.5 +/- 1.6 +/- 10(-10) M. By ultracentrifugation in sucrose gradient, two specific components with sedimentation coefficients of 8 and 4S are found. Competition studies suggest that the same specific binding sites may be present for estriol (E3) and for estradiol. The s.c. administration of E3 to the pregnant guinea pig (1 mg/day per kg body weight for 3 days) provokes two biological responses in the fetal uterus: a uterothopic effect and a significant increase in the progesterone receptor. The increase in the fetal uterine weight is 50-70% in relation to the non-treated animals and the progesterone receptor concentration is 10-14 times higher than in the control animals. These effects are similar (or slightly higher) than in animals primed with equimolecular quantities of estradiol. In contrast, single daily injections of E3 to newborn guinea pig, results only in weak uterotrophic activity. It is concluded that estriol is capable of causing a biological response in the uterus during intra-uterine life.

Animals↗