Biomedical subjects

M Nagano

Publications and source records attributed to M Nagano.

At least 109 records · Page 6Linked to original sources

PubMed1996

Pulmonary toxicity of systemic terbium chloride in mice.

Terbium (Tb) is a rare earth metal that finds use in several emerging technologies. However, little is known about the biological effects of Tb. Thus, in this study the pulmonary toxicity of systemic Tb in mice was investigated. Mice were treated intravenously with a single dose of 20 or 200 mumol Tb/kg, as TbCly and killed at 3, 6, 12, 24, 48, or 72 h later. Administration of Tb at a dose of 200 mumol/kg increased pulmonary weight, lipid peroxidation, and protein content but decreased pulmonary glutathione content. Pulmonary gamma-glutamyl transpeptidase (gamma-GTP) activity was increased after Tb administration at a dose of 200 mumol/kg. Pulmonary alkaline phosphatase (ALP) activity was also increased after Tb administration at a dose of 200 mumol/kg. Investigation of the defense system against oxidative damage in the lung showed that superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were all decreased after Tb administration at the higher dose. The concentrations of Tb, Ca, and P in lung was increased by the dose of 200 mumol/kg. These results suggest that pulmonary lipid peroxidation may be an early and sensitive consequence of Tb exposure and that SOD, CAT, and GSH-Px might be considered as potential modulators of Tb-induced lipid peroxidation. The mechanisms involved in Tb-induced pulmonary lipid peroxidation deserve further study.

Alkaline Phosphatase↗

PubMed1996

Differential promoter usage in prolactin receptor gene expression: hepatocyte nuclear factor 4 binds to and activates the promoter preferentially active in the liver.

Characterization of the rat PRL receptor (PRLR) gene has revealed three separate untranslated exon 1 sequences, each associated with a different transcription start site and 5'-flanking sequence. We show by RT-PCR that exon 1A is expressed primarily in liver but is also detectable in ovary and mammary gland. Exon 1B expression is observed exclusively in the ovary, whereas exon 1C is expressed in all three tissues. Transient transfection of luciferase reporter constructs containing parts of the 5'-flanking regions (0.3-1.1 kb) of exon 1A, 1B, and 1C, respectively, showed activity of the 1A promoter in Chinese hamster ovary (CHO) cells, the human hepatoma cell line, HepG2, and the rat hepatoma cell line, H4II, which was 10- to 14-fold increased compared with the activity of the promoter-less luciferase vector. No activity of the 1A promoter was detected in the human mammary cell line, T-47D. Relative to a vector containing the Simian virus 40 (SV40) promoter, the 1A promoter had 20% activity in H4II cells and 1-3% activity in CHO and HepG2 cells. The 1B promoter produced a 6.1-fold increase of luciferase activity in CHO cells (approximately 2% of the SV40 promoter), whereas no significant activity was detected in HepG2, H4II, and T-47D cells. The 1C promoter was strongly active in T-47D cells (approximately 64-fold over control) and moderately active in the other cell lines tested (9- to 13-fold over control). 5'-Deletion analysis of the 1A promoter revealed that a fragment containing -83/ +81 bp, relative to the transcription start site, was sufficient to drive transcription in hepatoma cells, whereas this construct was inactive in CHO cells. Cotransfection of CHO cells with the -83/+81 construct and an expression vector encoding the liver-enriched transcription factor, hepatocyte nuclear factor 4 (HNF4), revealed a dose-dependent transactivation of the proximal 1A promoter with a maximal stimulation of approximately 10-fold. Electrophoretic mobility shift assays showed binding of HNF4 to the sequence -14/+24 of the 1A promoter, and mutational analysis revealed that the sequence GGGCAAAGTCA at position +11/+21 is required for this binding. We conclude that the 1A, 1B, and 1C promoters of the PRLR gene are used in a cell type- dependent way that may play a role in differential hormonal regulation of the gene. In particular, we have shown that HNF4 operates on the proximal 1A promoter and may be responsible, in combination with other factors, for the increased activity of this promoter in adult female liver.

Animals↗

PubMed1996

Effects of extracellular matrix macromolecules on the differentiation of plasma membrane structure in cultured astrocytes.

Orthogonal aggregates of small intramembrane particles, termed "assemblies," are concentrated especially in the cell membranes of astrocytic processes that form the glia limitans at the outer surface of the brain and the perivascular sheath surrounding the parenchymal blood vessels. As an initial step to clarifying the totally unknown biochemical nature of this intramembrane structure, we have devised a culture system which enhances the differentiation of assemblies in secondary cultures of astrocytes derived from neonatal mouse neopallium. Since assemblies are most concentrated in the plasma membranes attaching to the basement membrane, we expected that extracellular matrix molecules constituting the basement membrane would be suitable candidates for our aim. We report here that a mixture of type IV collagen, laminin, and fibronectin, major components of the extracellular matrix, has the potency to increase assembly density in cultured astrocytes. We also report that, in freeze-fracture electron microscopy of cultured cells, one can satisfactorily preserve membrane structure and reliably obtain large replicas by inoculating cells on aluminium foil and peeling it from the cells in a freeze-fracture apparatus.

Animals↗

PubMed1996

[Effect of human serum albumin on transport of drugs through human erythrocyte membranes].

The binding properties to human serum albumin (HSA) and the transport of drugs through human erythrocyte membranes were examined with benzoic acid or its twenty-five derivatives (o-, m-, or p-hydroxybenzoic acid, o-, m-, or p-aminobenzoic acid, o-, m-, or p-nitrobenzoic acid, o-, m-, or p-toluic acid, o-, m-, or p-fluorobenzoic acid, o-, m-, or p-chlorobenzoic acid, o-, m-, or p-bromobenzoic acid, aspirin, salicyluric acid, alpha-resorcylic acid and gamma-resorcylic acid) and with glycosides (arbutin, salicin, glycyrrhizin and four p-nitrophenylglycosides) or their aglycons (hydroquinone, saligenin, glycyrretinic acid and p-nitrophenol). The drugs having hydroxyl group and amino group to o-site and those having nitro group, methyl group and halogen group to m- or p-site showed higher affinity with HSA and the plasma hindered the permeability of these drugs. The glycosides bind to each site (1, 2, and 3) of HSA more weakly than do their aglycons and they were difficult for plasma to hinder membrane permeation. The binding constants of each drug to HSA (Kb-site 1, Kb-site 2, Kb-site 3 and Kb-total) and the inhibition ratio (IR) related to the partition coefficient (P): Kb-site 1 (M-1) = 2.1479 x 10(3).square root of P - 5.2824.P + 2.0985 x 10(3) (R = 0.9371), Kb-site 2 (M-1) = 4.3741 x 10(3).square root of P - 15.2068.P + 6.5660 x 10(3) (R = 0.6788), Kb-site 3 (M-1) = 2.2176 x 10(4).log P + 1.2022 x 10(4) (R = 0.5227), Kb-total (M-1) = 1.0214 x 10(4).square root of P - 33.3721.P + 1.6919 x 10(4) (R = 0.7413), IR (%) = 19.885.log P + 17.916 (R = 0.8605). IR obtained from predictive equations (IR = 17.837.log P - 13.286. log Kb-site 1 + 0.175.square root of Kb-site 2 + 0.074.square root of K b-site 3 + 37.355, R = 0.9642, F = 71.4937***, ***; p < 0.001) by multiple regression analysis was compatible with experimental IR.

Benzoates↗

PubMed1996

[Clinical efficacy of fluconazole against fungal infections in hematological diseases].

Clinical efficacy of fluconazole was evaluated against fungal infections complicated with hematological diseases. Fluconazole 200 approximately 400 mg was administered intravenously to 20 suspected fungal infections occurring in patients with hematological diseases (acute leukemia 6, malignant lymphoma 11, adult T cell leukemia 2, chronic myelogenous leukemia blastic crisis 1). These mycoses included 8 cases of suspected pulmonary fungal infection, 10 cases suspected fungemia, and two cases of suspected hepatic fungal abscess. The clinical response rate was 60.0%. Side effects were observed in two cases, one with transient liver function test abnormality and the other with nausea. Fluconazole is considered to be a potent, safe antifungal agent for the treatment of suspected fungal infections associated with hematological diseases.

Adult↗

PubMed1996

[A questionnaire study on health administration in small enterprises in a rural region].

A questionnaire study on the health administration of industrial workers was performed on 230 enterprises in city A in a rural region. Responding subjects numbered 140 and the response rate was 60.9%. Subjects by scale were: 16% with more than 50 workers, 48% with from 10 to 49 workers and 36% with less than 10 workers, and the proportions by industry were: 32% manufacturing, 22% wholesale-retail trade and 14% construction. The subject proportions classified according to the health insurance scheme were: 59% government-managed health insurance, 15% national health insurance and 11% society-managed health insurance. The rate of periodic health examination was 100% in enterprises with more than 50 workers, 67.2% in those with from 10 to 49 workers and 51.0% in those with less than 10 workers. The main reasons why then did not receive health examinations were: 40% had no time available to conduct examinations, 21% believed such examinations were not necessary, and 19% did not know of such an examination system. They encountered some difficulties in promoting health; for example, the advanced age of workers, and no time or money to spare for health administration. They desired provision of facilities close at hand for health examination, health consultation and health information. The results of this study show the difficulty of promoting health administration in small scale enterprises and also that it is difficult to obtain accurate information on actUal conditions including health administration in small enterprises.

Exercise↗

PubMed1995

Preparation and characterization of recombinant prolactin receptor extracellular domain from rat.

Complementary (c)DNA of the extracellular domain of rat prolactin receptor (rPRLR-ECD) was cloned in the prokaryotic expression vector pTrc99A, and expressed in Escherichia coli following induction with isopropyl-b-D-thiogalactopyranoside. The expressed rPRLR-ECD protein, contained within the refractile body pellet was solubilized in 4.5 M urea, refolded and purified on a Q-Sepharose column by stepwise elution with NaCl. Only approximately 10% of the expressed protein refolded as a monomeric fraction, yielding 5-6 mg/l of induced culture. The purified protein was over 98% homogeneous, as shown by SDS-PAGE in the presence or absence of reducing agent, and by chromatography on a Superdex column. Its molecular mass, determined by SDS-PAGE in the absence of reducing agent, was 28 kDa, and by gel filtration, 25.6 kDa. Binding experiments indicated high affinity for bovine placental lactogen (bPL) and human growth hormone (hGH) as compared to ovine (o) or rat PRLs. Gel filtration was used to determine the stoichiometry of rPRLR-ECD's interaction with these hormones. At a 5 microM initial concentration of the hormones, formation of 2:1 (ECD:ligand) complexes was detected with bPL, hGH and oPRL whereas only 1:1 complex was formed with rPRL. Dilution (25-fold) of these complexes did not affect the stoichiometry with bPL, whereas with hGH a clear tendency towards dissociation of the initial 2:1 complex to 1:1 complex was observed. This tendency was even stronger in the case of oPRL. Although all four hormones exhibited nearly identical activities in the Nb2-11C lymphoma cell bioassay, the ability of the purified rat or rabbit PRLR-ECD to inhibit hormonal mitogenic activity generally reflected their affinity for the respective hormones. In view of these and former results, we suggest that unlike in the GH:GHR-ECD interaction, the inability of lactogenic hormones to form a 1:2 complex with soluble recombinant PRLR-ECDs does not necessarily predicts lack of biological activity.

Animals↗

PubMed1995

Early administration of YT-146, an adenosine A2 receptor agonist, inhibits neointimal thickening after rat femoral artery endothelium injury.

Adenosine is known to inhibit vascular smooth muscle cell proliferation in vitro via adenosine A2 receptor activation. We tested the inhibitory effect of an adenosine A2 receptor agonist, 2-octynyladenosine (YT-146), on in vivo intimal thickening following a photochemically induced injury of the endothelium of rat femoral artery. YT-146 (1 mg/kg/day) was administered s.c. for the first 3, 7 or 28 days after the injury. YT-146 significantly decreased neointimal area and the ratio of intima to medial area measured 28 days after the injury, regardless of the duration of administration. These results suggest that YT-146 may inhibit the early events of neointimal formation. The effect is long lasting and is not reversed even if YT-146 is stopped after a short course of administration.

Adenosine↗

PubMed1995

Characterization of high-density apolipoprotein particles A-I and A-I:A-II isolated from humans with cholesteryl ester transfer protein deficiency.

The cholesteryl ester transfer protein (CETP) plays an important role in metabolism of high-density lipoprotein and reverse cholesterol transport in humans. The two major classes of high-density lipoprotein particles are those containing apolipoprotein A-I (LpA-I) and those containing both apoA-I and apoA-II (LpA-I:A-II). We isolated and characterized the apoA-I-containing lipoprotein particles from three subjects with homozygous CETP deficiency (CETP-D) and compared the results with those from normolipidemic control subjects. Plasma concentrations of apoA-I in both LpA-I and LpA-I:A-II were significantly elevated in CETP-D subjects. Both LpA-I and LpA-I:A-II from these subjects were larger and contained more cholesteryl ester per particle than control particles. In CETP-D, subpopulations of LpA-I and LpA-I:A-II with an unusually large size (Stokes diameters 13.8 nm and 12.6 nm, respectively) not detected in normal subjects were isolated. The molar ratio of apoA-I to apoA-II in LpA-I:A-II isolated from CETP-D subjects was higher (mean 2.4) than those of controls (mean 1.4). ApoE was primarily associated with LpA-I:A-II in CETP-D subjects. A subclass of LpA-I with pre-beta migration on agarose electrophoresis was increased in CETP-D subjects. Both LpA-I and LpA-I:A-II from CETP-D subjects bound with higher affinity but less capacity to HepG2 cells compared with control particles, and were internalized to a lesser extent than control particles. These data suggest that the absence of CETP in humans significantly affects the plasma concentration, size, composition, and cellular interaction of both major classes of apoA-I-containing lipoprotein particles.

Adult↗

PubMed1995

Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1 disrupted mice.

Ad4BP (or SF-1) has been identified as a transcription factor which regulates all the steroidogenic P450 genes in the peripheral organs, and is encoded by the mammalian homologue of Drosophila FTZ-F1 gene. mRNA coding for Ad4BP was detected in the hypothalamus and pituitary of rats by RT-PCR. Immunohistochemical analyses using an antiserum to Ad4BP in the brain and pituitary revealed that the transcription factor is expressed in nuclei of the dorsomedial part of the ventromedial hypothalamus (dmVMH) and in some subpopulation of the adenohypophysial cells. Double immunostaining of the pituitary for Ad4BP and trophic peptide hormones, FSH, TSH, and ACTH, indicated a restricted localization of Ad4BP to the gonadotroph. Disruption of the mouse Ftz-F1 gene was clarified to induce severe defects in the organization of the dmVMH and the function of the pituitary gonadotroph. However, some of the dm VMH neurons and pituitary gonadotrophs persisted, which provided a sharp contrast to complete agenesis of the peripheral steroidogenic tissues (adrenal and gonads) in the mutant mouse. Additional abnormalities were seen in the ventrolateral part of VMH and dorsomedial hypothalamic nucleus, both of which do not express Ad4BP but have strong reciprocal fiber-connections with the dmVMH. Aromatase P450-containing cells in the medial preoptico-amygdaloid region, which were devoid of Ad4BP, persisted even in the brain of the gene disrupted mice. The present results clearly showed that the hypothalamic and pituitary Ad4BPs are essential to normal development of the functional VMH and gonadotroph through some mechanism distinct from that in the peripheral steroidogenic tissues.

Animals↗

PubMed1995

Monocyte-related cytokines in acute myocardial infarction.

To elucidate the role of monocytes in the cytokine system in acute myocardial infarction (AMI), we examined the time courses of plasma concentrations and generation capacities of monocyte-related cytokines in 17 consecutive patients with uncomplicated AMI (from day 1 to 28) and in 10 control subjects. The concentrations of monocyte-related cytokines were measured by enzyme immunoassay with horseradish peroxidase. Cytokine generation capacity was evaluated by cytokine concentrations in the culture solution 24 hours after incubation of 0.5 ml whole blood with 5 micrograms lipopolysaccharide. Two distinct patterns of increases in the cytokine concentrations were noted: transient (plasma interleukin [IL]-6) and sustained (plasma macrophage colony-stimulating factor and generation capacities of IL-1 alpha, IL-6, granulocyte colony-stimulating factor, and tumor necrosis factor alpha). There was no significant increase in the concentrations of other cytokines. These results indicate that the concentrations of the monocyte-related cytokines dynamically change during the course of AMI, suggesting that they may contribute to the inflammatory and subsequent proliferative responses in AMI.

Adult↗

PubMed1995

The influence of decreased left-ventricular afterload on cardiac morphology in hypertrophied rat hearts.

The influence of afterload reduction on cardiac morphology was investigated in Goldblatt rats (hypertensive Wistar rats) with left-ventricular hypertrophy. The measurements were performed on a modified heart-lung preparation in which left-ventricular afterload was reduced either 0%, 15%-30% or 35%-50%. Goldblatt rats without heart-lung preparation served as control group. The aim of this study was to investigate the effects of decreased left-ventricular afterload on the myocardial morphology. The hearts were prepared for light and electron microscopy. For ultrastructural investigations, we developed a mitochondrial alteration score and graded the myocytes according to the degree of ischemic injury. The changes ranged from score 0 (normal) to score 4 (most severe). The mean score of the group with marked afterload reduction (35%-50%) was significantly increased compared to all other groups. Our data suggest that marked afterload reduction has a negative impact on the myocardial ultrastructure in hypertension-induced left-ventricular hypertrophy. Light microscopically, we found a correlation between myocardial cell diameter and blood pressure and a significant difference in arterial wall thickness between normotensive and hypertensive rats.

Animals↗

PubMed1995

Molecular biological and quantitative abnormalities of ADP/ATP carrier protein in cardiomyopathic hamsters.

The adenine nucleotide translocator or ADP/ATP carrier protein (AAC) is an integral protein present in the inner mitochondrial membrane, which performs the exchange of cytoplasmic and intramitochondrial ADP and ATP. The myocardial AAC content was studied in J-2-N cardiomyopathic hamsters. The AAC content was found to be significantly decreased in J-2-N hamsters. For molecular biological analysis, hamster AAC (T1 isoenzyme) cDNA was cloned by the plaque hybridization method. This AAC cDNA hybridized specifically with AAC mRNA, so RNA dot-blot hybridization was performed. The highest AAC mRNA level was observed in control hamsters followed by J-2-N hamsters with mild myocardial damage, J-2-N hamsters with severe myocardial damage and Bio 14-6 cardiomyopathic hamsters. These results suggest that a decreased AAC content may contribute to the pathogenesis of cardiomyopathy and that a decrease of AAC mRNA levels may explain the abnormalities of AAC in J-2-N cardiomyopathic hamsters.

Animals↗

PubMed1995

Persistent inhibition of the pressor and aldosterone responses to angiotensin-II by TCV-116 in normotensive subjects.

TCV-116 is an orally active, nonpeptide antagonist of angiotensin-II type-1 receptor. The angiotensin-II antagonistic potency of TCV-116 was evaluated in normal volunteers. TCV-116 was administered at single doses of 1, 2.5, and 5 mg orally on separated days. Before, and 4, 8, and 24 h after the drug administration, angiotensin-II was infused intravenously at the rate of 2.5 to 40 ng/kg/min for 5 min each. At 2.5 mg of TCV-116, the pressor response to angiotensin-II was significantly suppressed at 4 and 8 hours after drug administration. TCV-116 at 5 mg produced a reduction of basal blood pressure and a suppression of pressor response to angiotensin-II, which persisted for 24 h. Aldosterone response to exogenous angiotensin-II was suppressed to 10% at 8 h after 5 mg of TCV-116 administration and remained suppressed to 48% until 24 h. These results suggest that TCV-116 is a highly potent and long-lasting antagonist of angiotensin-II receptor in man. The renin-angiotensin system may play a role in the regulation of blood pressure even in normotensive subjects.

Administration, Oral↗

PubMed1995

Expression of prolactin and growth hormone receptor genes and their isoforms in the gastrointestinal tract.

Distribution of transcripts for prolactin and growth hormone receptors (PRLR and GHR) and their isoforms was characterized in the gastrointestinal (GI) tract from several species by reverse transcription-polymerase chain reaction combined with Southern analysis. Human, rabbit, and fetal and adult rat PRLR and GHR transcripts were detected in isolated gastric glands, gastric cell fractions, and intestinal mucosa lineages. Human PRLR and GHR transcripts were also observed throughout the cancerous progression of the colonic and gastric mucosa from adenomas to colonic liver metastasis and gastrointestinal cancer cell lines at various stages of growth and differentiation. Prolactin (PRL) produced no detectable effect on M1 gastric mucin secretion in HT-29 cells adapted to methotrexate (HT-29-MTX) or on acid secretion in isolated rabbit parietal cells. GHRd3, an isoform of human GHR transcript missing exon 3, was also broadly expressed and was the only form found in gastric and colorectal adenocarcinomas. Interestingly, several extra bands of polymerase chain reaction products of the human PRLR, which were smaller than the expected size, were observed not only in the GI tract but also in liver and T-47D breast cancer cells. These products from human intestinal and breast cancer cell lines were subsequently subcloned and sequenced, and we isolated six isoforms of the receptor transcripts. One of these clones encodes a putative human PRL binding protein. The expression of PRL and PRLR transcripts was also clearly observed in intraepithelial lymphocytes purified from the mouse intestine. The widespread expression of the PRL and GH receptor transcripts in gastric and intestinal mucosal lineages, particularly in epithelia, suggests regulatory roles of these hormones on digestive and immune functions, including metabolism, growth, or differentiation.

Amino Acid Sequence↗

PubMed1995

Increased catabolic rate of low density lipoproteins in humans with cholesteryl ester transfer protein deficiency.

The cholesteryl ester transfer protein (CETP) transfers lipids among lipoprotein particles and plays a central role in lipoprotein metabolism. Humans with genetic deficiency of CETP have both elevated HDL cholesterol and apolipoprotein A-I concentrations as well as decreased LDL cholesterol and apolipoprotein B levels. The present study was undertaken to elucidate the metabolic basis for the decreased LDL cholesterol and apo B levels in CETP deficiency. We conducted a series of in vivo apo B kinetic studies in tow unrelated homozygotes with CETP deficiency and in control subjects. A primed constant infusion of stable isotopically labeled phenylalanine was administered to the two CETP deficient subjects and control subjects and apo B kinetic parameters in VLDL, intermediate density lipoproteins, and LDL were obtained by using a multicompartmental model. The fractional catabolic rates (FCR) of LDL apo B were significantly increased in the CETP-deficient subjects (0.56 and 0.75/d) compared with the controls (mean FCR of 0.39/d). Furthermore, the production rates of apo B in VLDL and intermediate density lipoprotein were decreased by 55% and 81%, respectively, in CETP deficiency compared with the controls. In conclusion, CETP-deficient subjects were demonstrated to have substantially increased catabolic rates of LDL apo B as the primary metabolic basis for the low plasma levels of LDL apo B. This result indicates that the LDL receptor pathway may be up-regulated in CETP deficiency.

Adult↗

PubMed1995

Regulation of prolactin receptor mRNA expression in peripheral lymphocytes in rats in response to changes in serum concentrations of prolactin.

In the present study we have evaluated the absolute number of the two forms of prolactin (PRL) receptor mRNA in rat peripheral blood lymphocytes and the modulation of receptor mRNA induced by changes in serum levels of endogenous PRL or by administration of ovine PRL. Lymphocytes expressed low levels of both forms of PRL receptor transcripts. Repeated treatments with ovine PRL significantly reduced levels of mRNA encoding the long form PRL receptor, whereas expression was markedly increased by repeated doses of bromocriptine. In contrast, the mRNA level of short form PRL receptor was unchanged by both treatments. The expression of long form transcripts was also markedly decreased in lymphocytes from pituitary-grafted rats. Therefore it appears that in rat peripheral lymphocytes PRL has a negative effect on the expression of its own receptor.

Animals↗

PubMed1995

Quantitative analysis by polymerase chain reaction of growth hormone receptor gene expression in human liver and muscle.

A single form of GH receptor (GHR) messenger RNA (mRNA) of 4.5 kilobases, encoding the full-length GHR, has been found in man. To measure the absolute number of mRNA molecules encoding the GHR in human tissues, we developed a quantitative polymerase chain reaction assay. An internal control RNA was constructed by inserting a 50-basepair fragment of the rat PRL receptor complementary DNA into a portion of the human GHR complementary DNA. The internal control RNA and the target mRNA were amplified together with the same set of primers. Twenty-four cycles of amplification were used to satisfy an exponential phase of amplification. It was possible to detect as few as 500 molecules of target mRNA/micrograms total RNA. In 3 liver samples obtained from normal donors at the time of transplant, the amount of GHR mRNA ranged from 0.5 +/- 0.1 to 1.4 +/- 0.4 x 10(6) molecules/micrograms total RNA. These results were confirmed by slot blot analysis of the same samples. The number of receptor transcripts did not appear to be correlated with the receptor-binding capacity found in the 3 liver samples. In 7 muscle biopsies, GH receptor mRNA varied between 4.0 +/- 0.4 and 34.6 +/- 1.4 x 10(4) molecules/micrograms total RNA. This technique allows direct measurement of GHR gene expression in human tissues and represents a valuable tool, particularly for tissues such as muscle, in which the receptor protein cannot be measured using conventional binding assays.

Base Sequence↗