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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this work was to determine whether dexamethasone (Dex), a synthetic glucocorticoid, counteracts the stimulatory effects of estradiol (E2) on MCF-7 cells. We have shown that Dex inhibits in a dose-dependent fashion the estradiol-stimulated cell proliferation. This inhibition (ID50 congruent to 5-10 nM), which is complete at 100 nM Dex, is prevented by the antiglucocorticoid RU 486 and is clearly different from that found with trans-4-OH-tamoxifen because the inhibition due to a fixed concentration of Dex is not abolished by a high concentration of estradiol. This inhibitory effect displays some degree of specificity. Progesterone and the progestins R 5020 and ORG 2058 are without effect and Dex does not alter the triiodo-L-thyronine-stimulated cell growth. To characterize further the antiestrogenic action of Dex, the effects of this drug on specific responses to estradiol were studied. (1) Among the positive responses to estradiol two are prevented by Dex (the increase of concentration of progestin receptors and that of immunoreactive insulin-like growth factor I, IR-IGF-I, in conditioned medium) and two are insensitive to Dex (the enhancement of the secretion of 52,000 and 160,000 Mr proteins). (2) A negative response to estradiol (the down-regulation of estrogen receptor) is not prevented but rather accentuated by Dex. Thus, Dex counteracts the stimulatory effects of estradiol on the proliferation of MCF-7 cell variants characterized by progestin insensitivity. This non-classical antiestrogenic effect could be due in part to the attenuation of the E2-induced IR-IGF-I secretion and, less probably, to the accentuation of the down-regulation of E2 receptors. It could account for certain therapeutic and/or side effects of glucocorticoids on estrogen target cells.
Mol Cell Endocrinol 1989 Oct
PMID:Non-classical antiestrogenic actions of dexamethasone in variant MCF-7 human breast cancer cells in culture. 261 31

We describe two apical surface integral membrane glycoproteins which appear to be differentiation markers of the human pulmonary alveolar type 2 cell which has as a major function the production of pulmonary surfactant. These membrane glycoproteins bind the lectin, Maclura pomifera agglutinin and can be found in detergent extract of whole lungs, lung membranes and isolated type 2 cells. One of the MPA binding glycoproteins (MPA-gp330) has an apparent molecular weight of 330 kD and is analogous to a similar membrane glycoprotein found in rat and rabbit type 2 cells. The other glycoprotein (MPA-gp350/390) is an antigen found on the surface of many human cancer cells. In studies of human fetal lung tissue we found that MPA-gp350/390 is expressed before known surfactant functions of the type 2 cell while MPA-gp330 appears later. Neither glycoprotein is influenced by glucocorticoids yet surfactant synthesis is hormone-dependent. These studies demonstrate that pulmonary type 2 cell differentiation is a more complex process than previously appreciated and that differentiation markers are expressed in a discoordinate fashion and regulated by different factors.
J Mol Cell Cardiol 1989 Feb
PMID:Alveolar cell differentiation markers in human lungs. 273 26

Granulosa cells from immature female rats, pretreated with pregnant mare's serum gonadotropin, were cultured with microcarrier beads for 24 h, and superfused with culture medium. Progesterone was transiently released following a 10-min pulse of FSH (100 ng/ml), and there was a self-priming effect of FSH. 10-min pulses of 8-bromo-adenosine 3',5'-cyclic monophosphate (8Br-cAMP) (1 mg/ml) mimicked the effects of follicle-stimulating hormone (FSH). Continuous superfusion with FSH induced biphasic secretion of progesterone, which was composed of a parabolic (the first) and a plateau (the second) phase. By contrast, the pattern of secretion induced by continuous superfusion with 8Br-cAMP was monophasic. FSH-stimulated secretion of progesterone was rapidly inhibited by the addition of 10 microM cycloheximide (CX), but secretion recovered upon removal of this inhibitor. In the second phase, the recovery of secretion was accompanied by an overshoot of the plateau value. The present results suggest that: (1) the generation of the time-related biphasic pattern of secretion cannot be interpreted by cAMP alone; (2) FSH stimulates the secretion of progesterone by a mechanism that involves newly synthesized protein.
Mol Cell Endocrinol 1988 Oct
PMID:Dynamic response to follicle-stimulating hormone of secretion of progesterone by superfused rat ovarian granulosa cells. 284 83

We describe the isolation of a cloned cDNA from a cDNA library of oviduct of estrogen-treated adult Xenopus. Although the protein encoded by this cDNA is not known, it is designated as FOSP-1 (frog oviduct-specific protein-1). A partial restriction map of FOSP-1 cDNA, which is 1.5 kb in size, is presented. Northern hybridization analysis showed that FOSP-1 cDNA codes for a single species of mRNA of 2.6 kb which is exclusively expressed in Xenopus oviduct. Southern blot analysis showed that the gene was present in only one or two copies. Sequencing of partial FOSP-1 cDNA did not reveal homology with any protein in the sequence data bank. Measurement of steady-state levels of FOSP-1 mRNA in primary cultures of Xenopus oviduct cells by a technique of quantitative slot-blot analysis showed that both 17 beta and 17 alpha stereoisomers of estradiol caused a rapid 5-fold enhancement of accumulation of the mRNA with maximum values obtained at 5 X 10(-8) M estrogen. Progesterone caused only a small increase in FOSP-1 mRNA concentration. This hormone-specific induction of mRNA makes FOSP-1 a valuable candidate for exploring tissue specificity of regulation by estrogen of gene expression.
Mol Cell Endocrinol 1988 Oct
PMID:FOSP-1 (frog oviduct-specific protein-1) gene: cloning of cDNA and induction by estrogen in primary cultures of Xenopus oviduct cells. 284 84

Cultured human endometrial stromal cells were found to release placental protein 5 (PP5), a glycoprotein with properties of a serine protease inhibitor. Progesterone had no effect on PP5 release, but cholera toxin and 12-O-tetradecanoylphorbol 13-acetate stimulated PP5 release in a time- and concentration-dependent fashion. Prostaglandin E2 (PGE2) caused a parallel increase in cAMP and PP5 release in a time- and concentration-dependent fashion. The lowest PGE2 concentration which increased cAMP and PP5 release was 1 X 10(-9) M. Maximal increase in cAMP (42-fold) and PP5 (25-fold) release was obtained by 10(-5) M PGE2. Stimulation of cAMP by PGE2 was detectable at 15 min and was followed by an increased PP5 release at 24 h. The concentrations of prostaglandin F2 alpha (PGF2 alpha) which stimulated cAMP and PP5 release were pharmacological suggesting that this effect is nonspecific. The results indicate that the activation of cAMP- and protein kinase C-dependent pathways in endometrial stromal cells increases the production of PP5. PGE2 could be one of the physiological ligands employing the cAMP-dependent pathway in endometrial stromal cells.
Mol Cell Endocrinol 1988 Dec
PMID:Regulation of the production of placental protein 5 by human endometrial stromal cells; the role of prostaglandins E2 and F2 alpha. 285 Sep 54

Estrogen has been shown to increase proenkephalin (PE) mRNA levels in neurons of the ventrolateral aspect of the ventromedial hypothalamic nucleus (VL-VM). In this series of experiments, we examined the temporal qualities of this induction by determining both the latency of the estrogen-induced elevation in PE mRNA levels and the rate at which the message levels decline following removal of estrogen. In addition we have examined the effects of progesterone on PE gene expression in the VL-VM of estrogen-primed rats. The latency of the estrogen-induced elevation in PE mRNA levels was found to be relatively short: PE mRNA levels were increased 2-fold within 1 h of estrogen replacement. Following estrogen removal the levels of PE mRNA declined rapidly. Progesterone treatment attenuated this decline, prolonging the estrogen-induced elevation of PE mRNA levels. These results suggest that estrogen rapidly increases PE mRNA levels through a mechanism that probably involves alterations in both the rate of appearance and the rate of degradation of the message. Together, the short latency of the estrogen-induced elevation and the rapid rate of decay following estrogen removal indicate that PE gene expression is highly sensitive to fluctuating estrogen levels. The effect of progesterone suggests that this enkephalinergic system may be regulated by both estrogen and progesterone during the estrous cycle.
Brain Res Mol Brain Res 1989 Jan
PMID:Estrogen regulation of proenkephalin gene expression in the ventromedial hypothalamus of the rat: temporal qualities and synergism with progesterone. 292 83

Treatment of 3T3-L1 preadipocytes (fibroblasts) with 250 nM dexamethasone for 48 hr caused a doubling of total beta-adrenergic receptors and an increase in beta 2-adrenergic receptor subtype proportion from approximately 50% in controls to 85% in treated cells. The responses to epinephrine and norepinephrine in a whole cell cAMP accumulation assay reflected these changes. The effects of dexamethasone on beta-adrenergic receptors were mediated through the glucocorticoid receptor and were time and dose dependent with an EC50 of 2.77 +/- 0.73 nM for an increase in the proportion of beta 2-adrenergic receptors. The rank order of potency of steroids to effect these changes (betamethasone = dexamethasone greater than fludrocortisone greater than hydrocortisone = triamcinolone greater than aldosterone) correlated with their glucocorticoid potency. [3H]Dexamethasone binding to intact cells yielded a KD value of 3.47 +/- 0.38 nM for binding to the glucocorticoid receptor which correlated well with the EC50 for dexamethasone to alter beta-adrenergic receptors. Inhibition of [3H]dexamethasone binding by other steroids confirmed that the ability of steroids to regulate beta-adrenergic receptors correlated with the affinity of each compound for the 3T3-L1 glucocorticoid receptor. Progesterone, which can bind to the glucocorticoid receptor but has only weak agonist activity, competitively inhibited the ability of dexamethasone to alter beta-adrenergic receptors. Protein synthesis, RNA synthesis, and N-linked glycosylation appeared to be necessary for the change in receptor subtype expression and the increase in beta-adrenergic receptor number induced by dexamethasone. The present study suggests that regulation of beta-adrenergic receptor expression in 3T3-L1 preadipocytes by dexamethasone is a glucocorticoid-specific effect which may require gene activation.
Mol Pharmacol 1987 Apr
PMID:Glucocorticoid regulation of beta-adrenergic receptors in 3T3-L1 preadipocytes. 303 66

To investigate the interaction of PRL and progesterone in regulating uterine gene expression, we have quantitated the concentration of PRL receptor and of uteroglobin (UG) mRNA in the endometrium of rabbits of different ages and after treatment with different hormones. During uterine differentiation in 2- to 4-week old rabbits, a marked increase in unoccupied uterine PRL receptor number was observed, presumably increasing uterine sensitivity to PRL. Receptor values for 4-week old rabbits were comparable to values for sexually mature, estrous females, but were lower than in 5-day pseudopregnant (PSP) animals. When total PRL receptor was determined by Scatchard analysis after in vitro desaturation with MgCl2, PSP animals again expressed the highest receptor concentration with no changes in the dissociation constant (Kd) values. To determine whether progesterone regulates uterine PRL receptor, long term ovariectomized rabbits (greater than 12 weeks) were treated with various combinations of hormones, and unoccupied and total uterine PRL receptors were determined. Progesterone treatment resulted in the highest concentration of both unoccupied and total PRL receptor after desaturation and removal of anti-ovine PRL antibodies with MgCl2. The value for total uterine PRL receptor was equivalent to the value for mammary gland, and the Kd values (2-4 x 10(-10) M) were similar. Treatment of long term ovariectomized rabbits with progesterone, with or without estradiol, produced an increase (P less than 0.05) in the UG mRNA content, which also occurred in PSP animals. PRL alone had no effect on UG mRNA but PRL plus progesterone increased (P less than 0.05) UG mRNA in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1988 Dec
PMID:Servomechanism of prolactin and progesterone in regulating uterine gene expression. 321 59

The objective of the present study was to investigate the effect of cell density on hormonal responsiveness and lipoprotein utilization by cultured bovine luteal cells. Luteal cells obtained from regularly cycling dairy cows were plated at three culture densities: 0.5 X 10(6), 1 X 10(6) and 2 X 10(6) cells/flask in serum-free Ham's F-12 culture medium, and maintained for 9 days. Basal steroidogenesis was unaffected by cell density, while LH responsiveness was greatest in low density cultures. Progesterone produced in response to LH (10 ng/ml) was greater than control levels throughout the culture period in low density cultures. Luteal cells cultured at medium and high densities became responsive to LH only later in the culture period (days 5 and 9, respectively). In contrast, prostaglandin F2 alpha (PGF2 alpha, 100 ng/ml) was more effective in high density cultures, causing a complete inhibition of LH stimulation and returning progesterone levels to basal values. In low density cultures, treatment with PGF2 alpha + LH resulted in progesterone levels that were not significantly different from LH-treated cultures. There was no effect of cell density on utilization of either low density lipoprotein (LDL) or high density lipoprotein (HDL) for steroidogenesis. However, a synergistic effect of LH with either lipoprotein was observed in low and medium density, but not high density cultures. From these results, it is concluded that culture density can influence the responsiveness of bovine luteal cells to either LH or PGF2 alpha, but has no effect on lipoprotein utilization by these cells.
Mol Cell Endocrinol 1987 Oct
PMID:Cell density influences hormonal responsiveness but not lipoprotein utilization in cultured bovine luteal cells. 347 77

The kinetics of estrogen (E) modulation of retinol-binding protein (RBP) production in the liver of immature chicks were compared with those governing de novo induction of riboflavin carrier protein (RCP) in the same tissue. A single dose of E markedly enhanced the plasma levels of RBP without any detectable lag period to reach peak value by 24 h and this was followed by a decline to attain the baseline by 4 days. There was no amplification of the response during secondary stimulation unlike the case with RCP induction. With multiple E administration, the 4-fold increased plasma RBP concentrations were sustained at a steady state during both primary and secondary stimulations, whereas concomitant RCP concentration progressively increased with each hormone administration and this response was further amplified during secondary stimulation. Unlike RCP induction, enhanced RBP accumulation was not strictly E dose dependent although a minimal threshold level of the steroid was required to elicit measurable response. Progesterone (P) could neither modulate nor substitute for E in enhancing plasma levels of either of the 2 proteins while the anti-estrogens, en- and zuclomifene citrate severely suppressed the production of both the proteins. RCP induction was completely inhibited by both alpha-amanitin and cycloheximide for prolonged periods while E-stimulated RBP production was affected only partially by alpha-amanitin. Likewise, cycloheximide inhibition of RBP accumulation followed a pattern similar to that of hepatic general protein synthesis.
Mol Cell Endocrinol 1986 Jul
PMID:Estrogen modulation of retinol-binding protein in immature chicks: comparison with riboflavin carrier protein. 372 Oct 58


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