Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ESTRADIOL”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,441 records · Page 80Linked to original sources
PubMed2005

Differential effects of estradiol, progesterone, and testosterone on vaginal structural integrity.

Ovarian steroids are known to be important in maintaining vaginal tissue, and evidence is mounting that imbalances in the hormonal milieu contribute to vaginal pathophysiology. To date, limited data are available on the effects of hormone deprivation and replacement on vaginal tissue morphology and vaginal innervation. The goal of this study was to assess the dynamic changes in vaginal tissue structure in response to sex steroid hormone deprivation and administration. Female Sprague-Dawley rats were either kept intact (controls) or ovariectomized. Ovariectomized animals were treated with vehicle, estradiol, testosterone, progesterone, or a combination of estradiol plus testosterone or progesterone. Histological techniques, including stereological analysis and immunohistochemistry for localization of neuronal markers, were used. Ovariectomy produced a significant decrease in epithelial height that was restored with estradiol replacement. Interestingly, a subphysiological dose of estradiol resulted in hyperplasia of the vaginal epithelium and nonvascular smooth muscle. Neither testosterone nor progesterone had a significant effect on epithelial height or muscularis thickness. However, testosterone treatment resulted in a significant increase in small adrenergic nerve fibers. Addition of either testosterone or progesterone to estradiol mitigated but did not abolish the effects of estradiol alone. This study demonstrates that estradiol and testosterone have differential effects on vaginal tissue parameters and that ovarian hormones are critical for the maintenance of genital tissue structure. Present observations also suggest that combined replacement regimens may be required for an optimal physiological response.

Animals↗
PubMed1978

Estradiol inhibition of luteinizing hormone-stimulated progesterone synthesis in isolated bovine luteal cells.

The effects of several steroid hormones on progesterone synthesis and cAMP accumulation in isolated bovine corpora luteal cells were investigated in an attempt to determine if any of the steroids would affect the basal level of these processes or their response to gonadotropin. Isolated bovine corpora luteal cells responded to LH with a significant (P less than 0.05) increase in progesterone synthesis and cAMP accumulation when incubated at 37 C for up to 1 h. Exogenous cAMP and analogs of cAMP also significantly stimulated steroidogenesis in these incubated cells. Stimulation of progesterone synthesis by 1 microgram/ml LH was significantly suppressed (P less than 0.05) in the presence of 5--10 microgram/ml estradiol. This inhibition appeared to be largely specific for 17beta-estradiol, in that other steroids such as estrone, estriol, 17alpha-estradiol, cortisol, and dihydrotestosterone were not inhibitory. Testosterone was found to be inhibitory, but it is uncertain if this effect was due to the androgen itself or to its conversion to estradiol. Estradiol did not affect the increase in endogenous cAMP caused by LH in these cells, but did inhibit the effect of exogenous dibutyryl cAMP on progesterone synthesis. The magnitude of this inhibition of the effect of dibutyryl cAMP was not, however, equal to the estradiol inhibition of the stimulation of progesterone synthesis by LH. These data indicate that estradiol, a possible physiological luteolytic agent, has a direct inhibitory action on the corpus luteum and produces its suppression by blocking the stimulatory effect of LH at a step after cAMP.

Animals↗
PubMed1980

The effect of 17 beta-estradiol on collagen and noncollagenous protein synthesis in the uterus and some periodontal tissues.

The effect of a single dose of 17 beta-estradiol on collagen metabolism in the uterus and various oral tissues was determined in ovariectomized nulliparous rats. Eight days after ovariectomy, 200-g rats were given 100 micrograms estradiol ip. Forty hours later, 2 mCi [3H]proline were administered by ip injection, and the animals were killed 2 h later. The specific radioactivities of hydroxyproline and proline in both salt-soluble and salt-insoluble proteins were used as a measure of collagen and noncollagenous protein metabolism. Estradiol was found to induce a 2-fold increase in the specific radioactivity of newly synthesized collagen and an 8-fold increase in the specific radioactivity of the insoluble collagen in the uterus. The discrepancy between these results could be largely accounted for by a 2- to 3-fold increase in the size of the newly synthesized collagen pool. Stimulation of noncollagenous protein synthesis was also observed. The total collagen content of the uterus was not significantly altered in estradiol-treated animals, suggesting that estradiol stimulates both the synthesis and degradation of collagen. Using [14C]glycine as a precursor, the nature of the collagens synthesized in the uterus was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Estradiol was found to stimulate the synthesis of both type I and type III collagens, but no change in the pattern of procollagen conversion could be discerned. In contrast to the uterine tissues, the only significant effect of estradiol on protein metabolism in the oral tissues was a decrease in the newly synthesized collagen specific radioactivity in the molar periodontal ligament.

Animals↗
PubMed1981

Mechanism by which 17 beta-estradiol inhibits ovarian androgen production in the rat.

The mechanism by which 17 beta-estradiol inhibits ovarian androgen biosynthesis was investigated. Immature 25-day-old rats were treated for 2 days with estradiol, after which whole ovaries were dispersed, and gonadotropin binding and cAMP and steroid hormone production were examined. When dispersed cells from untreated control ovaries were incubated with hCG (100 ng/ml), there were marked increases (10-fold) in steroid production, with the major steroids being progesterone and androstenedione. The stimulation of steroidogenesis by hCG was dose-related (ED50 = 100 pg/ml hCG). After 2 days of estradiol treatment, the maximum hCG stimulation of androstenedione, testosterone, 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone production by ovarian cells was inhibited by 90%; pregnenolone production was unchanged, while progesterone production was increased by 30%. Time course studies showed that the stimulatory effect of hCG on androgen production was maximally inhibited (90%) after 12 h of estradiol treatment. Implanting miniestradiol capsules unilaterally under the ovarian bursa caused a 77% decrease in the hCG stimulation of androgen production by the estradiol-treated cells, while progesterone production was unchanged. hCG-stimulated steroidogenesis in the contralateral ovary was not altered. Estradiol treatment did not affect the binding capacity, the hCG stimulation of cAMP production, or the number of steroid-producing cells in the ovaries. It is concluded from these experiments that exogenous estradiol acts directly on the rat ovary to abolish the hCG stimulation of androgen production by rapidly inhibiting 17 alpha-hydroxylation.

3-Hydroxysteroid Dehydrogenases↗
PubMed1982

Estradiol inhibits prolactin induced alpha-lactalbumin production in normal primate mammary tissue in vitro.

The effect of estradiol on prolactin induced alpha-lactalbumin production in normal primate mammary tissue was studied by maintaining tissues in organ culture with or without various combinations of oPRL and 17 beta-estradiol. As expected alpha-lactalbumin was increased byoPRL. 17 Beta-estradiol was found to have a significant inhibitory effect on oPRL-induced alpha-lactalbumin production. By 9 days in culture estradiol (10(-11) M) caused a mean 31% inhibition of prolactin-induced alpha-lactalbumin; with estradiol (10(-8) M) the inhibition was 40%. In the absence of oPRL, estradiol did not inhibit alpha-lactalbumin production. Thus it appears that estradiol directly antagonizes the lactogenic effect of prolactin on the normal primate mammary gland.

Animals↗
PubMed1983

Response to estradiol inhibition of tonic luteinizing hormone secretion decreases during the final stage of puberty in the rhesus monkey.

This investigation was conducted to determine if a decrease in responsiveness to estradiol inhibition of tonic LH secretion occurs in the female rhesus monkey during the late stages of sexual maturation. The study was conducted during the several month period between menarche and first ovulation. Serum LH was measured in postmenarchial females (n = 8) before and after ovariectomy and insertion of estradiol implants that achieved subadult concentrations (10-30 pg/ml) of the steroid. Removal of the ovaries 1-4 months after menarche (31 +/- 1 months) produced a prompt 3- to 5-fold rise in circulating LH. This was prevented by estradiol replacement therapy beginning at ovariectomy. Similarly, insertion of estradiol implants after the castration response was established decreased the high concentrations of circulating LH to preoperative levels where they remained for several months. At 42 +/- 1 months of age, and in the face of unchanging peripheral estradiol, circulating LH rose severalfold in the ovariectomized females (n = 7). At a similar age (44 +/- 2 months, n = 4), ovulations began in untreated females. The results indicate that subadult concentrations of peripheral estradiol which are capable of suppressing LH secretion before the age of first ovulation are ineffective in this regard afterward. This provides compelling evidence for a decrease in estradiol inhibition of tonic LH secretion during puberty in the primate female.

Age Factors↗
PubMed1983

Acute effects of estradiol on circulating luteinizing hormone and prolactin concentrations and on serotonin turnover in individual brain nuclei.

Two experiments tested whether serotonergic neurons participate in the acute feedback effects of estradiol on LH and PRL secretion. In the first study, ovariectomized female rats received oil vehicle or estradiol benzoate and were killed 3 h later. The turnover of serotonin [5-hydroxytryptamine (5-HT)] in microdissected brain nuclei was assessed from its accumulation after monoamine oxidase inhibition. Estradiol treatment produced a gradual rise in PRL and a decline in LH, and potentiated the accumulation of 5-HT in the medial preoptic, ventromedial, and cortical amygdaloid nuclei, suggesting increased turnover. Concentrations of the metabolite, 5-hydroxyindole acetic acid, were also elevated in these areas. 5-HT turnover was unaffected by estradiol in the interstitial nucleus of the stria terminalis, periventricular, dorsomedial, or lateral amygdaloid nuclei. The second experiment tested whether localized 5-HT depletions in these estradiol-activated nuclei blocked the acute effects of the steroid on LH or PRL. Stereotaxic microinjections of the 5-HT neurotoxin, 5,7, dihydroxytryptamine were made into the preoptic area, cortical amygdala, or medial basal hypothalamus in ovariectomized rats, pretreated with desmethylimipramine. Such treatment reduced 5-HT, without affecting catecholamines, in the targeted structures. Localized 5-HT depletion in the preoptic area and amygdala blunted the elevation of PRL, but not the decline of LH, after estradiol. 5-HT depletion in the medial basal hypothalamus elevated, whereas 5-HT depletion in the medial preoptic area lowered, resting levels of LH. These results suggest that: 1) estradiol may acutely increase PRL secretion by activating serotonergic projections to the medial preoptic and cortical amygdaloid nuclei, and 2) serotonergic neurons innervating the preoptic area stimulate LH release, whereas serotonergic systems in the medial basal hypothalamus inhibit LH release.

5,7-Dihydroxytryptamine↗
PubMed1985

Effects of estradiol on insulin receptor distribution in primary cultures of R3230AC mammary adenocarcinoma of the rat.

The influence of 17 beta-estradiol on insulin receptor distribution was studied in primary cultures of R3230AC mammary tumors prepared from intact or ovariectomized Fischer rats. [125I] Insulin binding to plasma membrane (IRS) and to solubilized cells (IRt) was measured, and intracellular insulin binding (IRi) was calculated by the difference between the two; calculated IRi agreed well with measured IRi of solubilized cells that were pretreated with trypsin to remove IRs. Scatchard analysis of saturation studies on IRs and IRt displayed typical curvilinearity and were roughly parallel with comparable Ke and Kd values for high affinity sites, but tumors from ovariectomized rats displayed more sites per cell. Insulin receptors relative to time in culture showed an early decline in IRt and IRs for both types of cells, followed by a gradual return to similar IRt values; in both types of cells, however, the proportion of IRs was increased compared to their initial distribution. Cells from both types of host animals displayed an insulin dose-related down-regulation with both IRt and IRs decreased. Short exposure (24 h) to 17 beta-estradiol in vitro also reduced IRs and IRt, but to a lesser extent than insulin, whereas longer exposure to estradiol (48 h) caused a continued reduction in IRs but not IRt. Compared to cells exposed to estradiol for 24 h in vitro, cultured cells treated with progesterone demonstrated an increased IRs, a marginal effect upon exposure to higher doses of testosterone, and reduced IRt, IRs, and IRi in response to dexamethasone. Monohydroxytamoxifen, an antiestrogen, displayed an unusual pattern, inducing a reduction in IRt and IRs at the lower doses but not at the higher doses studied. Degradation of [125I]insulin was examined in cells that were insulin down-regulated in the absence or presence of various levels of estradiol; the steroid hormone appeared to reduce degradation of [125I]insulin when lower levels of insulin were employed. The presence of estradiol in the medium enhanced the reappearance of IRt during the first 10 h after removal of the insulin that caused down-regulation. In conjunction with our previous observations in vivo, we conclude that 1) estradiol in vitro can decrease (down-regulate) insulin receptors on the plasma membrane of R3230AC mammary tumors; 2) the steroid may reduce degradation of internalized [125I]insulin; and 3) the steroid may enhance insulin receptor reappearance after insulin down-regulation. These estrogen-insulin interactions could play a role in the regulation of growth and metabolism of this hormone-responsive experimental mammary carcinoma.

Adenocarcinoma↗
PubMed1986

Estradiol suppression of luteinizing hormone (LH)/human chorionic gonadotropin receptors and LH-sensitive adenylyl cyclase without decreased adenosine 3',5'-monophosphate content in rabbit corpora lutea.

It has been observed that elevated concentrations of estradiol, the principle luteotropin in the rabbit, reduce LH-stimulated adenylyl cyclase activity in corpora lutea during midpseudopregnancy without suppressing serum and tissue progesterone concentrations. If LH modulates intraluteal cAMP levels in this species, this suggests that in the presence of exogenous estradiol, progesterone synthesis may be independent of cAMP. To test this possibility and to investigate the physiological significance of LH in regulating the rabbit corpus luteum, the concentrations of cAMP and progesterone and the activity of adenylyl cyclase were measured in luteal homogenates, the numbers of LH/hCG receptors were estimated in crude membrane preparations, and the concentrations of progesterone and estradiol were measured in serum on days 2-12 of pseudopregnancy in rabbits treated with or without estradiol. Throughout days 2-12 of pseudopregnancy, estradiol treatment increased LH-stimulated adenylyl cyclase activity on day 2, but reduced its activity after day 4 by up to 50%, reduced the number of LH/hCG receptors after day 2 by up to 50%, and had no effect on the activities of basal, epinephrine-stimulated, or NaF-stimulated adenylyl cyclase. Tissue cAMP levels were not altered by estradiol treatment, nor were serum progesterone concentrations (except for an increase on day 2). Since LH receptors and LH-stimulated adenylyl cyclase were both reduced by day 5 of pseudopregnancy without a concomitant decrease in luteal cAMP or serum progesterone concentrations, our data suggest that LH is not a physiological regulator of luteal cAMP or serum progesterone during days 4-12 of pseudopregnancy. We propose that basal adenylyl cyclase activity, which is not reduced by estradiol treatment, may play a more significant role than LH-stimulated adenylyl cyclase activity in regulating tissue cAMP levels and the progesterone synthetic capacity of the rabbit corpus luteum.

Adenylyl Cyclases↗
PubMed1987

Estradiol stimulation of glucose transport in rat uterus.

Glucose transport in rat uterus was investigated in order to determine whether the stimulation of transport by estradiol was the result of an increase in the amount of glucose transport protein in plasma membranes. In cycling rats, transport was highest during proestrus, the day on which serum estradiol concentrations are highest. In ovariectomized rats, the stimulation of transport was estrogen specific and was nearly complete within 2-3 h after injection of 0.1 microgram estradiol per animal. Estradiol stimulation resulted in a 2- to 3-fold increase in Vmax of 2-deoxy-D-glucose transport with no significant change in Michaelis-Menten constant (Km). Inhibition of the stimulation by cycloheximide or actinomycin D could not be demonstrated, although cycloheximide treatment did cause an increase in the basal rate of transport up to that observed with estradiol treatment. Upon polyacrylamide gel electrophoresis followed by Western blotting, a single protein in uterine plasma membranes reacted with a rabbit antiserum made against purified human erythrocyte glucose transport protein. This protein, believed to be the glucose transport protein, had a mol wt of 49,000 and appeared as a broad band as expected for a glycoprotein. It was found by a protein A-linked immunoassay that the amount of transport protein in uterine plasma membranes was 3.2 +/- 0.4% of the amount in human erythrocyte ghosts. Estradiol treatment had no effect on this value. These data suggest that the stimulation of glucose transport by estradiol occurred by an increase in the intrinsic activity of the transport protein rather than by an increase in the amount of transport protein in plasma membranes.

Animals↗
PubMed1988

Augmentation of the response of mouse uterine epithelial cells to estradiol by uterine stroma.

The effect of estrogen on the in vitro growth of mouse uterine epithelial cells was assessed. Epithelial cells from the immature mouse uterus were successfully cultivated in a 1:1 mixture of Dulbecco's Modified Eagle's Medium and Ham's F-12 supplemented with insulin (5 micrograms/ml), transferrin (10 micrograms/ml), hydrocortisone (10(-7) M), BSA (2 mg/ml), and fetuin (1 mg/ml). Addition of 17 beta-estradiol in the range of 1-100 nM did not significantly change the total DNA content of the epithelial cells. A binding component of [3H]estradiol by cultured uterine cells was shown to be specific, saturable, and of high affinity. Kd values for specific binding by epithelial and stromal cells were 1.0-1.7 x 10(-10) M. Maximal specific binding was 0.74 and 2.3 fmol/micrograms DNA for epithelial and stromal cells, respectively. Treatment of epithelial and stromal cells for 4 days with 10 nM estradiol led to a 2- to 6-fold increase in progesterone receptor concentration. Treatment of epithelial and stromal cells in mixed culture for 4 days with 10 nM estradiol resulted in a significant increase in total DNA. That epithelial-stromal contact was critical for estradiol stimulation was shown by the fact that if the cell types were separated into two compartments which still allowed free media mixing, total DNA was not enhanced by estradiol. These observations are organized into a model for mitogenic action of estradiol that seems to reconcile observed disparities in the action of the hormone in vivo and in vitro.

Animals↗
PubMed1989

Regulation of prolactin synthesis in vitro by estrogenic and antiestrogenic derivatives of estradiol and estrone.

The estrogenic and antiestrogenic activities of derivatives of estradiol and estrone were determined in vitro using the ability of primary cultures of immature rat pituitary cells to synthesize PRL. Estradiol derivatives were the most potent estrogens in the assay. Large ethinyl substitutions in the 17 alpha position generally caused a decrease in estrogenic potency (up to 1000-fold). The 3 phenolic hydroxyl was important, but not essential, for the estrogenic activity of the estradiol molecule. Estratriene was approximately 1000 times less potent than estradiol. However, significant estrogenic activity was observed with the compound anordin (EC50, 8 x 10(-9) M), which could potentially be converted to a dihydroxylated derivative but without an aromatic A ring. Similarly, the steroid androst-5-ene-3,17-diol was weakly estrogenic (EC50, 3 x 10(-8) M). Steriods with a ketone in the A and D rings were generally inactive as estrogens and antiestrogens. Estradiol derivatives with 17 beta amines were only weak estrogens. Estrone derivatives were less active than the corresponding estradiol derivatives. 4-Nitromethoxyestrone exhibited weak antiestrogenic properties; however, 4-nitroestrone and methoxyestrone were both estrogens. The reason for the antiestrogenic properties of 4-nitromethoxyestrone is obscure, as the compound does not have structural features similar to those of known nonsteroidal antiestrogens. Minor alterations to the estradiol molecule at the 11 beta (OH) or 6 (ketone) position had little effect on estrogenic potency; however, large substitutions at the 11 beta (RU 39,411) or 7 alpha (ICI 164384) position produced antiestrogenic compounds. RU 39,411 was approximately 10 times more active as an antiestrogen than 4-hydroxytamoxifen, whereas ICI 164,384 was approximately 10 times less active than 4-hydroxytamoxifen. A series of hypothetical models is proposed that could explain the antiestrogenic properties of RU 39,411 and ICI 164,384 by an interaction with the estrogen receptor steroid-binding site.

Animals↗
PubMed1989

Estradiol-stimulated increases in uterine eosinophils and nuclear type II estrogen-binding sites are prevented by pertussis toxin.

Previous studies from several laboratories have demonstrated that estradiol treatment resulted in an increase in nuclear type II binding sites. Our previous data suggest that this increase was due to the estradiol-stimulated influx of circulating eosinophils. Therefore, we suggested that the uterine nuclear type II estrogen-binding sites were not of uterine origin. In this report we present further evidence to support this hypothesis. Treatment of immature rats with estradiol resulted in the stimulation of several uterine parameters, namely wet weight, protein synthesis, eosinophil number, peroxidase activity, nuclear type II binding sites, and the synthesis and secretion of a 180-kDa protein. The coadministration of pertussigen had no effect on the estradiol-stimulated increase in wet weight, protein synthesis, or the synthesis and secretion of the 180-kDa protein. However, pertussigen did prevent the estradiol-stimulated increase in eosinophils, peroxidase activity, and nuclear type II binding sites, demonstrating a coordinated response. Since peroxidase activity is known to be contained int he eosinophil, these data are consistent with our earlier demonstration that the type II sites are of eosinophil origin. These data also support and extend our previous findings in neonatal animals that estradiol can stimulate a growth response without a corresponding increase in the nuclear type II binding sites. These results further indicate that the estradiol-stimulated increase in eosinophils does not appear to play a key role in the control of uterine growth.

Animals↗
PubMed1990

The effects of estradiol on the growth patterns of estrogen receptor-positive hypothalamic cell lines.

Although it appears that the perinatal development of sexual phenotype in the rodent brain is determined by exposure to estradiol, generated locally via aromatization of androgen, the mechanisms underlying this process are not fully understood. We have, therefore, developed an in vitro model of hormone action based upon examining the effects of sex steroids on SV-40-transformed fetal rat hypothalamic cell lines. Using serum-free growth factor-deficient conditions the effects of 17 alpha- and 17 beta-estradiol, testosterone, dihydrotestosterone (DHT), and tamoxifen on survival of two estrogen-binding rat hypothalamic cell lines were examined. In one cell line, RCF-8, both 17 beta-estradiol and testosterone increased survival at picomolar concentrations. This effect was blocked by tamoxifen, but could not be reproduced by the nonaromatizable androgen DHT or the inactive isomer 17 alpha-estradiol. In the other cell line, RCA-6, addition of 17 beta-estradiol led to inhibition of cellular proliferation, which was reversed by the addition of tamoxifen. In an estrogen receptor-negative hypothalamic cell line, RCF-12, estradiol had no net effect on the growth pattern. In summary, the estrogen-binding capacity and the responsiveness to physiological concentrations of estradiol and testosterone, but not DHT, make the RCF-8 cell line a potential in vitro model of hypothalamic sexual differentiation. The use of estrogen-sensitive hypothalamic cell lines provides a unique opportunity for studying the cellular mechanisms underlying this process.

Animals↗
PubMed1990

17 beta-estradiol stimulates the calbindin-D9k (CaBP9k) gene expression at the transcriptional and posttranscriptional levels in the rat uterus.

The 9 kilodalton vitamin D-dependent calcium-binding protein (CaBP9k), calbindin-D9k, is expressed in the intestine and uterus of mammals. Rat intestinal CaBP9k is a well documented expression of the steroid hormone like action of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). In contrast exogenous 1,25-(OH)2D3 does not affect the concentration of uterine CaBP9k which is dependent on estrogen. We have analyzed the effect of 17 beta-estradiol on the regulation of CaBP9k gene expression in the uterus of mature ovariectomized rats. CaBP9k mRNA is undetectable in the uterus of mature ovariectomized rats. A single dose of 17 beta-estradiol results in a detectable level of CaBP9k mRNA at 1 h and a significant increase 3 h after injection. The maximal CaBP9k mRNA level is reached 6 to 12 h post injection. These results show that 17 beta-estradiol increases CaBP9k production by increasing CaBP9k gene transcription. Chronic 17 beta-estradiol administration results in a plateau of CaBP9k mRNA but in a large increase in CaBP9k concentration. The kinetic response to a single estradiol injection was similar in immature rats. This result shows that no cellular differentiation is required for the control of CaBP9k gene expression by 17 beta-estradiol. The uterine cells of immature rats are already competent to respond optimally to estradiol. There is a single 0.5 kilobase CaBP9k gene transcript in the rat duodenum. In contrast there are two estrogen-inducible CaBP9k mRNA species in the uterus of both the mature ovariectomized and the immature rats. The smallest species corresponds to the duodenal CaBP9k mRNA species, while the larger species is at least 50 nucleotides larger. However, a unique CaBP9k identical to that in the duodenum is expressed in the uterus.

Animals↗
PubMed1991

Estradiol-17 beta stimulates DNA synthesis in rat granulosa cells: action mediated by transforming growth factor-beta.

Estradiol-17 beta is a mitogen in vivo for the proliferation of granulosa cells in the rat ovary. In this study we have shown that estradiol-17 beta acts on cultures of immature rat granulosa cells to stimulate DNA synthesis. DNA synthesis stimulated by estradiol-17 beta was enhanced by FSH. We have shown previously that transforming growth factor-beta (TGF-beta) stimulates DNA synthesis in rat granulosa cells in vitro and that this effect is augmented by FSH. The mitogenic action of estradiol-17 beta was mediated, at least in part, by a TGF-beta-like factor since in the presence of a neutralizing antibody to TGF-beta, DNA synthesis was attenuated. This conclusion was further supported by the novel finding that estradiol-17 beta stimulated the secretion of a TGF-beta-like factor by rat granulosa cells in culture. In summary, the evidence suggests that the actions of estradiol-17 beta and TGF-beta on DNA synthesis are interrelated, and that a TGF-beta-like factor mediates the mitogenic effects of estradiol-17 beta on rat granulosa cells.

Animals↗
PubMed1975

Induction of human endometrial estradiol dehydrogenase by progestins.

Estradiol-17beta dehydrogenase activity in proliferative human endometrium (average of 1.5 nmole of estrone formed from estradiol/mg protein/h) was stimulated as much as as 6-fold during incubations of tissue slices in culture medium containing progesterone. Stimulation was already detectable at 7 h and the highest activity values were reached at 48-72 h of incubation in the presence of excess progesterone. Maximal stimulation was achieved with concentrations of the hormone of 0.25 mug/ml or higher. At concentrations approximately equal to midluteal plasma levels (20 ng/ml) more than 50% of the maximal response was observed. Norgestrel (17alpha-ethynyl-18-methyl-19-nortestosterone) was also effective in inducing enzymatic activity. The similarity of the effects obtained with progesterone (a possible substrate for estradiol dehydrogenase) and the synthetic progestin indicates that the stimulation of enzymatic activity was not due to substrate induction. Addition of estradiol to the culture medium had no influence on the activity of the enzyme. The induction of estradiol dehydrogenase by progesterone was inhibited by puromycin or actinomycin D. These observations indicate that progestational agents increase the rate of de novo synthesis of the enzyme. Stimulation of endometrial estradiol dehydrogenase was also observed after 2-3 day oral administration of medroxyprogesterone acetate to women in the follicular phase. In contrast, the enzymatic activity in endometrium obtained from women taking estrogens was found to be as low as in normal proliferative tissue. These in vitro and in vivo results point to progesterone as the agent responsible for the 10-fold increase in endometrial estradiol dehydrogenase activity observed during the luteal phase in menstruating women. Data obtained from superfusion studies of estrogen dynamics in endometrium indicate that changes in enzyme concentrations may play a physiologic role in the regulation of tissue levels of estradiol.

Adenocarcinoma↗
PubMed1994

Dopaminergic structures in the ovine hypothalamus mediating estradiol negative feedback in anestrous ewes.

This study examined the role of two dopaminergic (DA) cell groups, the A-14 and A-15 DA groups, in the seasonal shift in the response of LH to estradiol negative feedback in ewes. Radiofrequency lesions were placed bilaterally, in the area of the A-15 or the ventromedial A-14 cell groups of ovariectomized ewes, while control animals underwent sham neurosurgery. The effect of estrogen was tested in anestrus by analyzing LH pulse patterns before and 3 and 10 days after the insertion of estradiol implants. To evaluate the effects of these lesions on DA inhibition of LH secretion, LH pulse patterns were compared before and after an iv injection of the DA antagonist pimozide on day 3 of estradiol treatment. LH pulses were also examined in these ewes during the breeding season before and 3 days after the insertion of estradiol implants. Also, the effect of the DA receptor agonist apomorphine was tested to determine any effect of lesions on DA receptors inhibitory to LH. Lesions in either the A-14 or A-15 area decreased, but did not completely abolish, estradiol inhibition of LH pulse frequency in anestrus. Both types of lesions also blocked the stimulatory effects of pimozide on LH pulse frequency in estradiol-treated ovariectomized anestrous ewes. During the breeding season, estrogen decreased LH pulse amplitude, but not frequency, in all groups. The DA receptor agonist apomorphine decreased LH pulse frequency in all groups. Furthermore, immunohistochemistry for tyrosine hydroxylase revealed catecholaminergic fibers apparently connecting the caudal A-14 and the rostral A-15 areas. These results suggest that both the A-14 and A-15 DA cell groups are involved in the inhibition of LH by estradiol in anestrous, but not breeding season, ewes. Seasonal shifts in the activity of these DA neurons may, thus, play a role in the annual reproductive cycle of the ewe.

Anestrus↗