Biomedical subjects

A Weisz

Publications and source records attributed to A Weisz.

At least 55 records · Page 3Linked to original sources

PubMed1993

Estrogen regulation of proto-oncogenes coding for nuclear proteins.

Estrogen hormones are known to exert a complex influence on development and function of the female reproductive organs of vertebrates by regulating cell growth and differentiation, as well as to be implicated in oncogenesis and maintenance of tumor growth. Estrogen acts on cells via interaction with an intracellular receptor, which, like all receptors for steroid hormones, is a trans-acting transcription enhancer factor activated by the cognate ligand and capable of binding to specific, cis-acting enhancer elements usually located within the 5'-flanking regions of target genes. Additionally, estrogen regulates gene expression by influencing mRNA stability or via interaction of the estrogen receptor with transcription regulatory factors. This article reviews data indicating that estrogen directly activates (primary activation) expression of proto-oncogenes codifying for nuclear proteins that, in turn, are responsible for indirect (secondary) activation of other genes. This cascade mechanism of gene activation is likely to progress for several more steps and allows us to envisage how estrogen can direct a complex task such as cell reproduction. Among proto-oncogenes codifying for nuclear proteins, we focus on fos, jun, myc, and related genes. The mechanisms of regulation of these genes by estrogen, including regulation of transcription, messenger RNA stabilization, and protein-protein interaction, are reviewed.

Animals↗

PubMed1992

Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes.

The promoter regions of many interferon-inducible genes share a short DNA sequence motif, termed the interferon consensus sequence (ICS) to which several regulatory proteins bind. A murine cDNA which encodes an ICS binding protein has been reported (M-ICSBP). The cloning of the human homologue of ICSBP (H-ICSBP) is described. H-ICSBP shares high sequence homology with its murine cognate. The derived sequence of H-ICSBP reveals restricted homology within the first 120 amino acids to three other interferon regulatory factors, IRF-1, IRF-2, and ISGF3 gamma. Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS, indicating that at least part of the DNA binding domain is located within the well conserved amino terminus. H-ICSBP is expressed exclusively in cell lines of hematopoietic origin. The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. Furthermore, either interferon-gamma (IFN-gamma) or IFN-beta can alleviate the repression mediated by ICSBP. Therefore, ICSBP may be involved in maintaining submaximal transcriptional activity of IFN-inducible genes in hematopoietic cells. IFN treatment would then alleviate repression allowing maximal transcriptional activity of these genes.

Amino Acid Sequence↗

PubMed1992

Complementary use of counter-current chromatography and preparative reversed-phase high-performance liquid chromatography in the separation of a synthetic mixture of brominated tetrachlorofluoresceins.

A synthetically prepared mixture of brominated 4,5,6,7-tetrachlorofloresceins was separated by a combination of preparative reversed-phase high-performance liquid chromatography and high-speed counter-current chromatography. Two new lower-brominated subsidiary colors of D&C Red Nos. 27 and 28 (phloxine B), 4',5'-dibromo-4, 5,6,7-tetrachlorofluorescein and 2',4',5'-tribromo-4,5,6, 7-tetrachlorofluorescein, were isolated and characterized by 1H NMR and chemical ionization mass spectrometry.

Chromatography, High Pressure Liquid↗

PubMed1992

Pulmonary deposition of inhaled terbutaline: comparison of scanning gamma camera and urinary excretion methods.

Deposition from a multidose powder inhaler (Turbuhaler, Astra) delivering 500 micrograms of terbutaline sulfate per metered dose was compared by two techniques in a group of six healthy volunteers. The deposition of the radionuclide 99mTc, which was used to label terbutaline sulfate powder, was quantified by gamma camera (G-method). Simultaneously, the gastrointestinal absorption of swallowed drug was blocked with activated charcoal, and the amount of terbutaline in a urine sample, collected over a period of 48 h and corrected by a pharmacokinetic internal standard of intravenous deuterated terbutaline, was used as a measure of lung deposition (U-method). The mean (standard deviation) depositions in lung were 26.9 (3.8%) of the dose for the G-method and 21.1 (3.2)% of the dose for the U-method. Possible reasons for the differences between the two means are discussed. Both methods are suitable for assessing deposition from medical aerosol inhalers; the U-method requires access to gas chromatography-mass spectrometric equipment, and the G-method requires access to gamma camera facilities.

Administration, Inhalation↗

PubMed1992

Transcriptional activation of jun and actin genes by estrogen during mitogenic stimulation of rat uterine cells.

Estrogens induce transcriptional activation of c-fos and c-myc proto-oncogenes during mitogenic stimulation of human, chicken, mouse and rat cells in vivo and in vitro. In this paper we show that 17 beta-estradiol injected into adult ovariectomized rats increases c-jun, jun-B and jun-D gene transcription in the uterus. Kinetics and amplitude of response are different for each gene, since c-jun is activated first, within 30 min after injection, followed by jun-D and jun-B, 60 and 90 min after injection, respectively. Maximal activation of jun-B marks a drop in transcription of all the jun genes. Furthermore, transcriptional activation by 17 beta-estradiol of the growth-regulated beta- and gamma-cytoskeletal actin genes is prevented by an inhibitor of protein synthesis, indicating that it is a secondary response to the hormone. These data support the hypothesis that during growth stimulation of target cells the estrogen receptor induces transcription of regulatory genes, triggering in this way a cascade of gene regulation events that results in progression through the cell cycle.

Actins↗

PubMed1991

Estrogen induces c-fos expression specifically in the luminal and glandular epithelia of adult rat uterus.

It was previously shown that injection of 17 beta-estradiol into adult ovariectomized rats induces a rapid and transient increase of c-fos gene transcription in the uterus. Immunohistochemical analysis now shows that estrogen activates c-fos specifically in the luminal and glandular epithelial cells of the endometrium, which are the only uterine cells responding to the hormone with DNA synthesis and cell proliferation, and not in estrogen receptor positive stromal and myometrial cells. This finding suggests that c-fos is involved in the mechanism of estrogen regulation of uterine epithelial cell proliferation and, furthermore, that the c-fos activation by estrogen is cell type dependent.

Animals↗

PubMed1991

Preparative purification of tetrabromotetrachlorofluorescein and phloxine B by centrifugal counter-current chromatography.

A centrifugal counter-current chromatographic method for preparative purification of commercial tetrabromotetrachlorofluorescein and Phloxine B (D&C Red Nos. 27 and 28, respectively) was developed. Ethyl acetate-n-butanol-0.01 M ammonium acetate (1:1:2) was used as the two-phase solvent system. Each purification trial involved 50 mg of sample and yielded 22 mg (+/- 2 mg) of pure dye. The purity of the product was measured by high-performance liquid and thin-layer chromatography and was found to be 99.9%. The partition coefficients of these compounds were found to be highly concentration-dependent in the two-phase solvent system used. If this problem can be circumvented, then the counter-current chromatographic method can be extended for use with gram quantities of dye.

1-Butanol↗

PubMed1990

Inverse relationship between poly (ADP-ribose) polymerase activity and 2',5'-oligoadenylates core level in estrogen-treated immature rat.

The activity of poly (ADP-ribose) polymerase (ADPRP) and the content of 2',5'-oligodenylates core (2',5'An; n = 2,3 and 4) were measured in homogenates of the uterus and of the liver of immature rats immediately before (time 0) or at different times after injection of estradiol-valerate. ADPRP activity increased gradually, starting 6 hours after estrogen injection, for about 4 days. Instead, the content of 2',5'An decreased by about 50% within 6 hours, and thereafter more slowly for 4 days to about 20% of starting values. Estrogen increased ADPRP activity and decreased 2',5'An concentration also in the kidney and in the cardiac muscle of the same animals, but not in the skeletal muscle, where neither of the two parameters was affected. Injection of vehicle only (sesame oil) had no effect on ADPRP activity nor on 2',5'An content of immature rat tissues.

Adenine Nucleotides↗

PubMed1990

Identification of an estrogen response element upstream of the human c-fos gene that binds the estrogen receptor and the AP-1 transcription factor.

Transcription of the proto-oncogene c-fos is stimulated by 17 beta-estradiol in estrogen responsive human and rat cells. To understand the molecular mechanisms of estrogen regulation of c-fos gene transcription, the human c-fos gene promoter, with 2.25 Kb of 5'-flanking DNA, was cloned upstream of the bacterial CAT gene and tested for estrogen regulation by transient transfection in HeLa cells. When an expression vector coding for the human estrogen receptor was co-transfected with the fos -CAT reporter, the promoter was found to respond to 17 beta-estradiol. An element responsible for estrogen induction was mapped in a 240 bp region localized 1060 to 1300 bases upstream of the startsite of transcription of the gene. Sequence analysis revealed, clustered in a 19 bp sub-region, a sequence corresponding to an imperfectly palindromic ERE: CGGCAGCGTGACC and two sequences: CTGAG and GTGAC, homologous to the core sequence of AP-1 transcription factor binding sites. A synthetic oligonucleotide reproducing this sub-region binds 'in vitro' both the estrogen receptor and AP-1 factor(s) and confers estrogen-responsivity to the HSV-tk gene promoter. Transcriptional activation by the estrogen receptor is prevented by mutations in the fos ERE that hamper binding of the receptor in vitro. Activation of the c-fos gene promoter in HeLa cells requires the DNA binding domain of the estrogen receptor, and can be achieved independently by the TAF-1 and the TAF-2 transcriptional activation functions of this molecule. A receptor mutant lacking the hormone binding domain can activate the c-fos gene promoter in the absence of estrogen.

Base Sequence↗

PubMed1990

Activation of 'immediate-early' genes by estrogen is not sufficient to achieve stimulation of DNA synthesis in rat uterus.

17 beta-estradiol, a long acting estrogen that is mitogenic for rat uterus in vivo, or the short acting estrogens estriol and 16 alpha-estradiol, not mitogenic on their own, were injected into adult, castrated rats and their effect on uterine gene expression and rate of DNA synthesis were compared. All three compounds increased steady-state mRNA concentration of c-fos, c-jun and c-myc proto-oncogenes to comparable levels (2 hrs after treatment), whereas only 17 beta-estradiol was found to stimulate significantly DNA synthesis (20-22 hrs later). Based on the different retention time of the tested estrogens in rat tissues, it is concluded that a short exposure to the hormone is sufficient to render uterine cells competent to progress through the cell cycle, via activation of 'immediate-early' genes expression, but that stimulation of DNA synthesis requires further changes, achieved via a prolonged exposure of the cells to the estrogenic stimulus.

Animals↗

PubMed1990

Estrogen stimulates transcription of c-jun protooncogene.

Estrogen is a mitogen for the rat uterus, where it induces transient activation of c-fos and c-myc protooncogene expression, followed by increases in DNA synthesis and cell proliferation. JUN-C, the product of the c-jun protooncogene, is a nuclear protein that can interact with FOS to modulate the activity of AP-1-responsive promoters. To test whether c-jun is a target for estrogen regulation, we measured the effects of 17 beta-estradiol on the expression of this gene in rat uterus. A human c-jun cDNA probe detects in rat uterus two mRNA species of 2.5 and 3.2 kilobases. Treatment of the animals with estrogen results in a rapid transient increase in the concentrations of these mRNAs; a 4- to 5-fold increase over the prestimulation level was detected starting 30 min after estrogen injection and lasting for 2 h, with a return to the prestimulation level after 4 h. In accordance with the results obtained by analysis of the mRNA, we found that estrogen increases 3- to 4-fold c-jun gene transcription in the uterus, at the same time it induces its mRNA accumulation. The ability of estrogen to induce c-jun gene expression was not abolished by the protein synthesis inhibitor cycloheximide, suggesting that transcriptional activation of this protooncogene is a primary response to the hormone. Furthermore, we found that in the estrogen-responsive MCF-7 human mammary carcinoma cells, estrogen stimulates transcription of a reporter gene containing four copies of a jun/AP-1 response element. These data demonstrate that c-jun gene expression is regulated by estrogen and suggest that JUN-C could play a role in the activation of cell proliferation by estrogen.

Animals↗

PubMed1988

Estrogen induces expression of c-fos and c-myc protooncogenes in rat uterus.

Estrogen stimulates DNA synthesis and cell proliferation in the luminal and glandular epithelia of rodent uterus. We tested the hypothesis that the mitogenic effect of estrogen occurs via activation of the expression of cellular proto-oncogenes by measuring the rate of transcription of 20 proto-oncogenes (abl, bas, erb-A, erb-B, ets, fms, fos, fps/fes, mos, myb, myc, N-myc, raf, Ha-ras, Ki-ras, N-ras, rel, sis, src, and B-lym) in the uterus of ovariectomized rats before and after injection of estrogen. c-onc transcriptional activity was monitored both by an in vitro transcription assay on isolated nuclei (run-on) and by analysis of mature mRNA. c-fos and c-myc proto-oncogenes were found to respond to estrogen with increased expression: c-fos within 30 min, with a first, sharp peak at 2 h and c-myc within 1.5 h, with a first, broad peak at 4-6 h. DNA synthesis start to increase in the uterus 13 h after estrogen injection and show a first peak at 24 h. In the liver and muscle of the same animals there is neither elevation of c-fos and c-myc expression nor increase of DNA synthesis. The kinetics of the induction by estrogen of c-fos gene expression in the uterus parallels the rate of formation of active nuclear estrogen-receptor complex. Furthermore, the ability of estrogen to induce c-fos mRNA was not abolished by the protein synthesis inhibitor cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

The development of amine substituted analogues of MPTP as unique tools for the study of MPTP toxicity and Parkinson's disease.

We are currently developing amino-substituted MPTP analogues as useful probes for understanding the mechanism of MPTP toxicity and Parkinson's disease. One analogue, 4'-amino MPTP, induces a loss of striatal dopamine and is thus a suitable substitute for MPTP. This probe will be used as a histologically fixable MPTP which can be used to answer detailed anatomical questions concerning the sites of MPTP, MPP+ uptake and storage. In addition, antibodies have been raised against MPTP and MPP+ in rabbits using diazo-linked bovine serum albumin conjugates. The antibodies have been characterized with regard to their recognition of relevant structural analogues using an enzymelinked immunoassay (ELISA) procedure. Antibodies to MPTP detected MPTP in mouse brain extracts derived from as little as 5 micrograms of tissue. The antibodies will be used for immunohistochemical localization of 4'-NH2-MPTP and 4'-NH2-MPP+ in brain, as well as probes for the screening of parkinsonian brain tissue for any MPTP- or MPP+-like materials which might exist.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1986

Specific binding of estrogen receptor to sites upstream and within the transcribed region of the chicken ovalbumin gene.

By means of the DNA-cellulose competitive binding assay, the interaction of estrogen receptor complexed to 17 beta-estradiol with fragments of a cloned DNA region of the estrogen responsive chicken ovalbumin gene spanning from 1343 bps upstream to 373 bps within the transcribed region of the gene (p0V 1.7) was investigated. Only DNA fragments including either the 5'-flanking region from -21 to -140 bps or the region within the gene from +41 to +143 bps showed binding affinity for the estrogen receptor higher than calf thymus DNA. DNA fragments from human alpha 1-globin gene and glucocorticoid responsive murine mammary tumor provirus corresponding to the same DNA region investigated for ovalbumin showed affinity for the estrogen receptor no higher than that of calf thymus DNA. These results suggest that two specific binding sites for estrogen receptor are located upstream and within the ovalbumin gene, near the start-site of transcription. These receptor binding sites overlap with the 'estrogen response element' identified by Dean et al. (1) and the DNase I Hypersensitive region I found by Kaye et al. (2).

Animals↗

PubMed1986

Mineralcorticoid receptor from rat kidney. Interaction with heparin and purification to a CBG-free stage.

Purification of the mineralcorticoid receptor is a particularly challenging problem. This receptor is present in target tissues at concentrations lower and is less stable than any other steroid receptor. Addition of molybdate ions (20 mM) to rat kidney cytosol enhances stability of mineralcorticoid-specific binding sites: the inactivation rate at 0 degrees C decreases from 7.2 to 1.7% per hour in the absence of aldosterone, and from 1.8 to 0.3% per hour in the presence of hormone. Rates of inactivation in the presence of molybdate are thus compatible with purification procedures. Also, the corticosteroid-binding globulin (CBG) is an important contaminating component of kidney cytosol because it cannot be specifically blocked preliminarily to affinity chromatography. We show that when kidney cytosol is incubated with heparin covalently linked to Sepharose (Sepharose-heparin), after 30 min at 0 degrees C more than 80% of the mineralcorticoid-specific binding sites interact strongly with Sepharose-heparin while CBG is not bound at all. The mineralcorticoid-specific binding sites can be recovered from Sepharose-heparin by washing with heparin (2 mg/ml; recovery up to 90%), KCl (0.3 M; recovery up to 90%); and, less efficiently, with total liver RNA (2 mg/ml; recovery up to 55%) and dextran sulfate (2 mg/ml; recovery up to 40%); little or no recovery is achieved with chondroitin sulfate, sonicated DNA, pyridoxal-5-phosphate, dextran, d-glucosamine and d-glucuronic acid. With demonstration that also the mineral-corticoid receptor binds to heparin, this property has become a general hallmark of steroid receptors. If the "heparin" binding site of steroid receptors is of physiological significance it remains to be established. By application of the newly found property of the mineralcorticoid receptor, an overall 10-fold purified, CBG-free preparation of this receptor can be obtained from kidney cytosol with a single chromatography on Sepharose-heparin.

Aldosterone↗

PubMed1985

Role of parathyroid hormone in the glucose intolerance of chronic renal failure.

Evidence has accumulated suggesting that the state of secondary hyperparathyroidism and the elevated blood levels of parathyroid hormone (PTH) in uremia participate in the genesis of many uremic manifestations. The present study examined the role of PTH in glucose intolerance of chronic renal failure (CRF). Intravenous glucose tolerance tests (IVGTT) and euglycemic and hyperglycemic clamp studies were performed in dogs with CRF with (NPX) and without parathyroid glands (NPX-PTX). There were no significant differences among the plasma concentrations of electrolytes, degree of CRF, and its duration. The serum levels of PTH were elevated in NPX and undetectable in NPX-PTX. The NPX dogs displayed glucose intolerance after CRF and blood glucose concentrations during IVGTT were significantly (P less than 0.01) higher than corresponding values before CRF. In contrast, blood glucose levels after IVGTT in NPX-PTX before and after CRF were not different. K-g rate fell after CRF from 2.86 +/- 0.48 to 1.23 +/- 0.18%/min (P less than 0.01) in NPX but remained unchanged in NPX-PTX (from 2.41 +/- 0.43 to 2.86 +/- 0.86%/min) dogs. Blood insulin levels after IVGTT in NPX-PTX were more than twice higher than in NPX animals (P less than 0.01) and for any given level of blood glucose concentration, the insulin levels were higher in NPX-PTX than NPX dogs. Clamp studies showed that the total amount of glucose utilized was significantly lower (P less than 0.025) in NPX (6.64 +/- 1.13 mg/kg X min) than in NPX-PTX (10.74 +/- 1.1 mg/kg X min) dogs. The early, late, and total insulin responses were significantly (P less than 0.025) greater in the NPX-PTX than NPX animals. The values for the total response were 143 +/- 28 vs. 71 +/- 10 microU/ml, P less than 0.01. There was no significant difference in the ratio of glucose metabolized to the total insulin response, a measure of tissue sensitivity to insulin, between the two groups. The glucose metabolized to total insulin response ratio in NPX (5.12 +/- 0.76 mg/kg X min per microU/ml) and NPX-PTX (5.18 +/- 0.57 mg/kg X min per microU/ml) dogs was not different but significantly (P less than 0.01) lower than in normal animals (9.98 +/- 1.26 mg/kg X min per microU/ml). The metabolic clearance rate of insulin was significantly (P less than 0.02) reduced in both NPX (12.1 +/- 0.7 ml/kg X min) and NPX-PTX (12.1 +/- 0.9 ml/kg X min) dogs, as compared with normal animals (17.4 +/- 1.8 ml/kg X min). The basal hepatic glucose production was similar in both groups of animals and nor different from normal dogs; both the time course and the magnitude of suppression of hepatic glucose production by insulin were similar in both in groups. There were no differences in the binding affinity, binding sites concentration, and binding capacity of monocytes to insulin among NPX, NPX-PTX, and normal dogs. The data show that (a) glucose intolerance does not develop with CRF in the absence of PTH, (b) PTH does not affect metabolic clearance of insulin or tissue resistance to insulin in CRF, and (c) the normalization of metabolism in CRF in the absence of PTH is due to increased insulin secretion. The results indicate that excess PTH in CRF interferes with the ability of the beta-cells to augment insulin secretion appropriately in response to the insulin-resistant state.

Animals↗

PubMed1984

Interaction of rat liver glucocorticoid receptor with heparin.

When rat liver cytosol containing [3H]dexamethasone-glucocorticoid receptor complex is exposed to immobilized heparin (Sepharose-heparin; Seph-hep) the steroid receptor complex binds to the substituted Sepharose avidly [Kd = 3.5 (+/- 1.7) X 10(-10) M], and 80-90% of the receptor present is adsorbed to the solid phase after 40 min at 0 degree C. The binding is enhanced by Mn2+ (10 mM) and Mg2+, whereas Ca2+ and Sr2+ are ineffective. Sodium molybdate (10 mM) does not influence the reaction but enhances receptor stability. Moreover, binding of the receptor to Seph-hep is dependent on the ionic strength of the medium, because binding is totally reversed by 300 mM KCl. The bound [3H]dexamethasone-receptor complex can be recovered from Seph-hep with solutions (4 mg/mL) of heparin (95% release), dextran sulfate (88%), and chondroitin sulfate (63%); total calf liver RNA is less effective (9%), whereas dextran, D-glucosamine, N-acetyl-D-glucosamine, D-glucuronic acid, and sheared calf thymus DNA are totally ineffective (less than 3%). Both "native" and temperature "transformed" forms of the glucocorticoid receptor interact with immobilized heparin. These results strongly suggest that the receptor site that binds heparin is distinct from that binding DNA. An immediate application of this newly found ability of the glucocorticoid receptor to interact with heparin is the use of Seph-hep for affinity chromatography purification of the glucocorticoid receptor. A purification of 10-fold, with a recovery of 55-65%, can be achieved by using either 4 mg/mL heparin or 300 mM KCl to elute [3H]dexamethasone-receptor bound to the resin.

Animals↗

PubMed1984

Mechanisms of glucocorticoid hormone action.

This work summarizes some of our studies of the mechanisms of glucocorticoid action, including aspects of steroid binding to receptors, the activation of glucocorticoid-receptor complexes and the regulation of expression of endogenous and transferred glucocorticoid-responsive genes. Studies of the receptor-steroid interaction support the notion that steroid entry is passive. A comparative analysis of binding in isolated cytosol and intact cells suggests that the initial receptor-steroid binding reaction and not subsequent steps such as activation and nuclear binding, is predominantly responsible for the high-affinity state that is generated. The binding is driven by entropy and enthalpy changes at low temperature; at higher temperatures it is driven by entropy changes, with enthalpy working against it. Studies of the activation of the receptor-glucocorticoid complex with the use of highly purified receptors suggest that this step is associated with a change in charge of the receptor-glucocorticoid complex (such as would occur with a dephosphorylation reaction), whereas the data do not support the notion that dissociation of a bound RNA or of receptor oligomers is responsible for generating the nuclear- and DNA-binding activity of the complex. Studies of the regulation by glucocorticoids of expression of the endogenous rat growth hormone (rGH) gene in cultured rat pituitary tumor (GC, GH3D6) cells suggest that glucocorticoids increase the expression of this gene by multiple mechanisms. First, there is a modest direct stimulation of transcription by a mechanism(s) that does not depend on protein synthesis; however, if the cells have been exposed to thyroid hormone for several hours, the steroid exerts a much greater increase in rGH pre-mRNA levels. Secondly, the steroid appears to stimulate some relatively stable function or functions that increase the ability of thyroid hormone to increase rGH levels. Thirdly, the steroid probably increases rGH mRNA stability, since the fold-increases in rGH mRNA exceed those of transcription. Finally, the steroid may, by unknown mechanisms, affect rGH mRNA polyadenylation. The gene transfer experiments utilized the rat and human (h) GH genes and hybrid genes containing either rGH and Herpes Simplex virus thymidine kinase (TK) gene sequences or the human metallothionein-IIA (hMT-IIA) and TK gene sequences. The steroid was found to regulate hMT-IIA gene expression in all glucocorticoid-responsive cell types tested by actions on its 5'-flanking DNA. By contrast, the glucocorticoid regulated GH gene expression in some but not all glucocorticoid-responsive cell types.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗