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PubMed1993

Modulation of systemic interleukin-6 induction by central interleukin-1.

Centrally administered interleukin (IL)-1 [both alpha and beta forms, 200 ng/rat intracerebroventricularly (icv)] results in a larger increase in serum IL-6 than after systemic injection, indicating the brain's role in the acute phase response. This action was prevented by the IL-1-receptor antagonist IL-1Ra (20 micrograms/rat icv). Neither antiserum against corticotropin-releasing factor (CRF) nor the alpha-helical-CRF antagonist (25 micrograms/rat icv) affected IL-6 induction by central IL-1 beta, which, however, was significantly prevented by the synthetic glucocorticoid dexamethasone [3 mg/kg intraperitoneally (ip)]. Naloxone, the opiate antagonist, but not naloxone methiodide, its quaternary salt that does not penetrate the blood-brain barrier (both administered at 10 mg/kg ip), antagonized this action of IL-1 beta. After intracerebroventricular IL-1 beta, IL-6 levels in brain areas (striatum, hippocampus, hypothalamus) were extremely low, suggesting that the brain does not significantly contribute to IL-6 synthesis in this condition. The results show that induction of high serum IL-6 levels by central IL-1 beta is mediated by brain IL-1 receptors and is sensitive to inhibition by corticosteroids. The inhibitory effect of naloxone suggests that central opiates are required for this action of IL-1 beta.

Animals↗

PubMed1993

Increased role of skeletal muscle in the calorigenic response to glucagon of cold-acclimated ducklings.

The site of the calorigenesis observed in birds after glucagon was sought in control and cold-acclimated (CA) ducklings. Twenty-four 6-wk-old muscovy ducklings were reared either at thermoneutrality (TN) (25 degrees C) or in the cold (4 degrees C) from the age of 1 wk. Glucagon-induced calorigenesis (GIC) was estimated at 25 degrees C after a peritoneal glucagon injection (103 nmol/kg). Glucagon induced a higher increase in animal heat production (indirect calorimetry) and body temperature in CA (+45% and +1.1 degrees C) than in control ducklings (+30% and +0.4 degree C). In CA ducklings, the perfusion rate (thermal clearance method) and temperature of gastrocnemius increased (+130% and +1.0 degree C) shortly after glucagon, whereas tissue oxygenation (polarography) decreased (-34%). There was no significant effect of glucagon in TN controls. These changes, which peaked 45-60 min after glucagon injection, indicated a prolonged increase of muscle O2 consumption in CA ducklings. Leg muscle blood flow (radioactive microspheres) measured 45 min after glucagon was slightly increased in controls (+20%; P < 0.05), while in CA ducklings, the increase was larger (+76%; P < 0.05). The arteriovenous difference in O2 content was not markedly affected by glucagon in both groups. These parameters indicated an increase in leg muscle O2 uptake in response to glucagon of +29% in controls and +76% in CA ducklings. In controls, 28% of the GIC measured in vivo could be attributed to whole body skeletal muscles, compared with 53% in CA ducklings. The remaining part might be accounted for mostly by the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

PubMed1995

Estimation of the pulmonary capillary transport function in isolated rabbit lungs.

Recently, we presented a method for estimating the pulmonary capillary volume and transport function based on the use of a reference indicator and two or more indicators that rapidly equilibrate (radially) with the tissue (i.e., the concentrations in the vascular and extravascular spaces at a given axial location are in equilibrium) during transit through the capillaries in a bolus-injection indicator dilution method (S. H. Audi, G. S. Krenz, J. H. Linehan, D. A. Rickaby, and C. A. Dawson. J. Appl. Physiol. 77:332-351, 1994). The objectives of the present study were 1) to determine whether [14C]diazepam and [3H]alfentanil equilibrate sufficiently rapidly between the vascular space and tissue and with sufficiently different pulmonary extra-vascular mean residence times to be used in a single bolus to estimate the pulmonary capillary volume and transport function using this method and 2) to estimate the pulmonary capillary volume and transit time distribution in isolated perfused rabbit lungs. Both [14C]diazepam and [3H]alfentanil were found to be rapidly equilibrating indicators by the criteria that, over a wide range of flow rates, their respective venous effluent concentration curves were nearly congruent on a time scale normalized to the lung mean transit time for the reference indicator (fluorescein isothiocyanate dextran). In addition, at a given plasma albumin concentration, [14C]diazepam had a significantly longer extravascular mean residence time than [3H]alfentanil, e.g., at 6% plasma albumin concentration, the extravascular mean residence time of [14C]diazepam was more than twice that of [3H]alfentanil. On average, the estimated pulmonary capillary volume for a 2.7-kg was approximately 4.2 ml or approximately 44% of the total pulmonary vascular volume (9.5 ml). The relative dispersion of the pulmonary capillary transport function of the rabbit was approximately 90%.

Alfentanil↗

PubMed1986

Transcapillary exchange in the hindlimb and intestine of dogs with right heart failure.

The effects of chronic right ventricular volume overload, congestive heart failure (HF) on transcapillary exchange of lipid-insoluble solutes in the hindlimb and small intestine were studied in anesthetized dogs. Using the single injection indicator diffusion method, extractions (E), capillary clearances (C), and capillary permeability surface area products (PS) of urea, sucrose, and inulin were measured in the hindlimb and small intestine of 16 control and 14 HF dogs. Right HF was caused by surgically produced tricuspid insufficiency. The HF dogs exhibited increased central venous pressures, right ventricular end diastolic pressure, and heart rates as well as gross ascites and pleural effusion. The small intestine of the HF dogs demonstrated increased E, C and PS values for all three solutes, while no changes were seen in the hindlimb. These changes in the capillary bed of the small intestine could be due to an increase in capillary permeability, and/or capillary surface area.

Animals↗

PubMed1981

Increased pulmonary vascular permeability after bone marrow injection in sheep.

We determined the effects of injection of bone marrow into the pulmonary circulation on pulmonary fluid and protein exchange in sheep. We also assessed the roles of free fatty acid toxicity and secondary thrombosis as mediators of the changes in pulmonary fluid balance. Injection of small amounts of bone marrow (range 0.07 to 0.41 ml/kg) resulted in pulmonary edema associated with increases in steady-state pulmonary lymph flow and protein clearance that the characteristic of increased endothelial permeability. There was no change in plasma concentrations of free fatty acids after injection. The small increases in lymph fatty acid clearance paralleled the increases in lymph protein clearance, reflecting the rapid binding of fatty acids to albumin. Decreased plasma fibrinogen with a concomitant increase in fibrin degradation products followed the bone marrow injection, indicating the activation of intravascular coagulation. In addition, the leukocyte count rapidly decreased just after the bone marrow injection. These findings suggest that the increased permeability was due to intravascular coagulation and resultant fibrin entrapment and leukostasis, and was not a result of increased circulating fatty acids.

Albumins↗

PubMed1987

Maintenance of the normal rat alveolar macrophage cell population. The roles of monocyte influx and alveolar macrophage proliferation in situ.

We investigated the relative importance of monocyte influx and alveolar macrophage proliferation in maintenance of the alveolar macrophage population in normal rats. Two experimental approaches were used. To detect possible monocyte influx, we radiolabeled blood monocytes by a continuous infusion of tritiated thymidine for 7 days and assayed lavaged alveolar macrophages for radiolabel by autoradiography. Although heavily labeled monocytes occurred in the blood, no heavily labeled cells were detectable among lavaged alveolar macrophages by cohort analysis. To evaluate macrophage proliferation in vivo, we injected normal unlabeled rats with colchicine and examined lavaged alveolar macrophages for arrested mitoses. Mitotic figures were observed among lavaged alveolar macrophages, and calculations at serial times after colchicine injection indicated that 1.83% of alveolar macrophages entered mitosis each day. On the basis of these 2 lines of evidence, we conclude that the alveolar macrophage cell population in normal rats is supported mainly by cellular proliferation in situ rather than direct monocyte influx from the blood compartment.

Animals↗

PubMed1970

Renal tubular protein absorption in the rat.

Radioiodinated protein solutions, 20 nl in volume, were injected into surface proximal and distal convoluted tubules of the rat kidney. The unabsorbed fraction was collected in ureteral urine, and the percentage recovered was expressed as a function of the injection site. Recovery increased progressively from more distal sites of injection indicating absorption along the proximal tubule of human serum albumin, insulin, and ribonuclease. Fractional absorption of albumin along the proximal tubule varied from 0 to 20% of the injected load, and was similar when the injectate concentration was 20, 40, or 100 mg/100 ml. Fractional absorption along the proximal tubule of insulin and ribonuclease, smaller proteins, was 30 to 50% of the injected load, and was similar with insulin concentrations of 0.09 mg/100 ml and 40 mg/100 ml and ribonuclease concentration of 40 mg/100 ml. In addition to this constant fractional absorption of each protein in the proximal tubule, smaller amounts were absorbed when injections were made in distal convoluted tubules.

Absorption↗

PubMed1970

Effect of colchicine on intestinal disaccharidases: correlation with biochemical aspects of cellular renewal.

There was a significant depression of the activities of intestinal lactase, invertase, and alkaline phosphatase in rats given drinking water containing 2.5 mg of colchicine per 100 ml. Activities of intestinal maltase, aspartate transcarbamylase, and dihydroorotase were not affected by the drug. Injection of colchicine (1 mg/kg) caused depression of intestinal invertase activity within 8 hr. Investigation of the effect of colchicine on the disaccharides in vitro demonstrated that invertase and maltase were not affected by concentrations up to 125 mg/100 ml. Intestinal lactase was inhibited by concentrations exceeding 5 mg/100 ml. Calculation of the concentration of colchicine present in the intestine, after a single injection, indicated that the in vivo effect of colchicine was not due to simple enzyme inhibition. Histological examination showed an increase in crypt cells but no decrease in the length of the villi. Cellular migration along the villi, as well as activity of uridine kinase in intestinal mucosa, was increased in colchicine-treated rats. It was concluded that colchicine did not depress intestinal invertase, lactase, and alkaline phosphatase by decreasing cellular renewal, but rather it exerted its effect directly on the differentiated cells of the villus.

Alkaline Phosphatase↗

PubMed1988

Role of the direct and indirect pathways for glycogen synthesis in rat liver in the postprandial state.

The pathway for hepatic glycogen synthesis in the postprandial state was studied in meal-fed rats chronically cannulated in the portal vein. Plasma glucose concentration in the portal vein was found to be 4.50 +/- 1.01 mM (mean +/- SE; n = 3) before a meal and 11.54 +/- 0.70 mM (mean +/- SE; n = 4) after a meal in rats meal-fed a diet consisting of 100% commercial rat chow for 7 d. The hepatic-portal difference of plasma glucose concentration showed that liver released glucose in the fasted state and either extracted or released glucose after feeding depending on plasma glucose concentration in the portal vein. The concentration of portal vein glucose at which liver changes from glucose releasing to glucose uptake was 8 mM, the Km of glucokinase [E.C. 2.7.1.12]. The rate of glycogen synthesis in liver during meal-feeding was found to be approximately 1 mumol glucosyl U/g wet wt/min in rats meal-fed a 50% glucose supplemented chow diet. The relative importance of the direct vs. indirect pathway for the replenishment of hepatic glycogen was determined by the incorporation of [3-3H,U-14C]glucose into liver glycogen. Labeled glucose was injected into the portal vein at the end of meal-feeding. The ratio of 3H/14C in the glucosyl units of glycogen was found to be 83-92% of the ratio in liver free glucose six minutes after the injection, indicating that the majority of exogenous glucose incorporated into glycogen did not go through glycolysis. The percent contribution of the direct versus indirect pathway was quantitated from the difference in the relative specific activity (RSA) of [3H] and [14C]-glycogen in rats infused with [3-3H,U-14C]glucose. No significant difference was found between the RSA of [3H]glycogen and [14C]glycogen, indicating further that the pathway for glycogen synthesis in liver from exogenous glucose is from the direct pathway. Our results do not support the thesis that the majority of liver glycogen is synthesized from glucose-6-phosphate derived from gluconeogenesis. Reasons for the discrepancy between current findings and other reports supporting the indirect pathway for glycogen synthesis in the liver are discussed.

Animals↗

PubMed1990

Administration of endotoxin, tumor necrosis factor, or interleukin 1 to rats activates skeletal muscle branched-chain alpha-keto acid dehydrogenase.

Protein catabolic states (i.e., sepsis and trauma) are thought to be associated with accelerated oxidation of branched-chain amino acids (BCAA). Branched-chain alpha-keto acid dehydrogenase (BCKAD), the rate-limiting enzyme for BCAA oxidation by muscle, is regulated by phosphorylation/dephosphorylation. Skeletal muscle BCKAD was only 2-4% active in control rats. Intravenous injection of Salmonella enteritidis endotoxin (0.25-10 mg/kg) did not change total BCKAD activity, but increased the percent active enzyme in muscle three- to four-fold in 4-6 h. Identical results were observed in adrenalectomized rats pretreated with one dose of alpha-methylprednisolone (2.5 mg/kg i.p.) 30-60 min before saline or endotoxin injection, indicating that endotoxin's effect was not mediated by hypersecretion of adrenal hormones. Cortisone pretreatment of normal rats (100 mg/kg per d) for 2 d prevented endotoxin-induced activation of muscle BCKAD, suggesting that endogenous secretion products mediated BCKAD activation by endotoxin. Human recombinant tumor necrosis factor-alpha and/or IL-1 beta or alpha (50 micrograms/kg) increased muscle BCKAD activation two- to fourfold in normal rats 4-6 h after intravenous injection. We conclude that cytokine-mediated activation of muscle BCKAD may contribute to accelerated BCAA oxidation in septicemia.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed1993

Development and transfer of immediate cutaneous hypersensitivity in mice exposed to aerosolized antigen.

We previously showed that BALB/c mice sensitized to ovalbumin (OVA) by brief daily inhalations of antigen over 10 consecutive days exhibit elevated antigen-specific serum IgE antibody levels and increased airways responsiveness. For the first time, we now show that animals sensitized in this fashion to either OVA or ragweed (RGW) develop immediate hypersensitivity skin test reactions when challenged 2 d after completion of the sensitization protocol. Skin testing, performed by direct assessment of wheal formation after intradermal injection of allergen, was sensitive and specific, since animals exposed to RGW by inhalation only responded to RGW, and OVA-sensitized animals responded only to OVA. Positive reactions were associated with mast cell degranulation, whereas control injections were not. Since only sensitized IgE high responder BALB/c mice but neither nonsensitized BALB/c mice nor OVA-sensitized IgE low responder SJL/J mice exhibited wheal responses, induction of OVA-specific IgE appeared to be essential for the mediation of OVA-specific immediate hypersensitivity reactions of the skin in this model. Passive cutaneous anaphylaxis (PCA) testing confirmed the presence of antigen-specific IgE in the serum. Mice that developed IgG (predominantly IgG2b) anti-OVA antibodies did not respond to OVA injection, indicating that OVA-specific IgG was not involved in this system. Further support for the role of IgE in the immediate hypersensitivity response included the wheal response to intradermal injection of anti-IgE antibody that occurred in OVA- and RGW-sensitized mice at 10-fold lower concentrations than in nonsensitized BALB/c mice and not in sensitized SJL/J mice. After transfer of mononuclear cells from peribronchial lymph nodes of OVA- or RGW-sensitized BALB/c mice, naive, syngeneic recipients developed antigen-specific IgE and specific immediate hypersensitivity responses, indicating that the local lymphoid tissue at the site of sensitization can transfer responsiveness to these allergens. These results demonstrate for the first time the ability to elicit and study IgE-mediated immediate skin hypersensitivity responses in the mouse and illustrate the association of increased antigen-specific and total serum IgE levels, airways hyperresponsiveness, and antigen-specific immediate cutaneous reactivity after sensitization to allergen via the airways.

Aerosols↗

PubMed1990

Development of newly formed nephrons in the goldfish kidney following hexachlorobutadiene-induced nephrotoxicity.

New nephrons developed in goldfish, Carassius auratus, several weeks following hexachlorobutadiene-induced (HCBD) nephrotoxicity. Basophilic clusters of presumptive nephrogenic cells incorporated 5-bromo, 2'deoxyuridine (BrdU) one week after HCBD injection, indicating initiation of DNA synthesis. These clusters, like renal vesicles in the developing kidney, elongated, fused with collecting ducts and developed into immature nephrons during the next 2 weeks. Stereologic quantification showed the volume percent of the kidney occupied by the developing nephrons was greater in HCBD-treated fish 2, 3, 4, and 10 weeks after injection than in the control fish. The presence of large numbers of developing nephrons may provide a marker for renal injury in fish from contaminated waterways.

Animals↗

PubMed1977

Effect of maternal malnutrition on matrix cell proliferation in the cerebrum of mouse embryo: an autoradiographic study.

Thirty pregnant mice were undernourished by providing low protein diets (PM) or providing approximately one-third their normal diets (PCM) for 9 days from the 8th to the 16th day of gestation. Another 15 pregnant mice, which were fed a normal diet, served as the control. On the 16th day of gestation, all animals were injected with a single does of [3H]thymidine and were killed one by one at 1- or 2-hr intervals. Mean litter size was statistically insignificant between the control group and two malnourished groups. There was, however, a significant difference in mean body weight between the control group and two malnourished groups (P less than 0.005). The cerebral cortex at this stage of development consisted of three different layers, i.e., the cortical plate, the migratory zone, and the matrix layer. The width of the cortical plate of the malnourished embryos was significantly smaller (P less than 0.001). There was, however, no significant difference in width of the migratory zone between the control and the malnourished groups. The width of the matrix layer in PM was significantly smaller (P less than 0.001), but that of PCM showed no significant difference from the control (P greater than 0.1). Coronal section of the brains of the embryos were processed for autoradiography. Labeled cells were found almost exclusively at the matrix layer surrounding the lateral ventricels. Labeling index counted in the matrix layer after 1 or 2 hr of [3H]thymidine injection indicated that more than 30% of the cells in this layer were always synthesizing DNA in each group of embryos. The generation times of the matrix cell, precursor of the neurons, in the matrix layer were approximately 18.5 hr in the control and 21.5 hr and 21.8 hr in the malnourished embryos, thus indicating about 3 hr of prolongation in the latter. DNA synthetic time was about 6.5 hr in the control and 7.0 hr and 7.0 hr in the two malnourished groups. The postduplication time was about 2.5 hr in the control and 3.0 hr and 3.5 hr in the malnourished. The preduplication time was about 8.8 hr in the control and 10.6 hr and 10.3 hr in the malnourished.

Animals↗

PubMed1983

Separate negative feedback effects of estrogen on the pituitary and the central nervous system in the ovariectomized rhesus monkey.

The site(s) of the negative feedback action of estrogen on gonadotropin secretion were studied in the ovariectomized rhesus monkey by observing the serum LH and FSH responses to intravenous GnRH injections at various times after implantation of Silastic capsules filled with estrogen. Circulating estrogen concentrations produced by the capsules were within the normal midcycle range for this species. Four h after estrogen implantation, no LH or FSH response was seen to the GnRH injection, indicating a suppressive effect of the steroid directly on the pituitary. Twelve and 22 h after estrogen implantation, however, the LH and FSH responses were equal to or larger than control responses. Since preinjection LH and FSH levels were below control values at these times and the pituitary responded to exogenous GnRH, it appears that endogenous GnRH secretion was affected, indicating an inhibitory action of estrogen on the central nervous system. Thus these experiments suggest 2 separate negative feedback actions of estrogen: a transient one directly on the pituitary and a longer lasting effect on the central nervous system.

Animals↗

PubMed1988

The effects of cortisol, vasopressin (AVP), and corticotropin-releasing factor administration on pulsatile adrenocorticotropin, alpha-melanocyte-stimulating hormone, and AVP secretion in the pituitary venous effluent of the horse.

Plasma ACTH, arginine vasopressin (AVP), and alpha MSH were measured in pituitary venous effluent at 5-min intervals from five unanesthetized horses during cortisol infusion and after an iv bolus of AVP or ovine (o) CRF. In control experiments (no hormone) there was a significant overall correlation between the timing of concentration changes in ACTH and alpha MSH. Cortisol infusion increased jugular cortisol levels by 70% and was associated with a reduction in mean ACTH, AVP, and alpha MSH secretion rates and ACTH peak secretion rate, but did not alter the observed pulse frequencies of these hormones. Administration of AVP raised plasma concentrations to a level comparable to the spontaneous peaks in pituitary venous blood and resulted in an increase in the secretion of ACTH and alpha MSH in all horses. Furthermore, spontaneous AVP peaks occurred in pituitary venous blood between 90 and 180 min after AVP injection, indicating that the exogenous hormone did not suppress AVP secretion. oCRF administration led to a prolonged elevation in plasma CRF and an increase in secretion of ACTH and alpha MSH, but not AVP, in all horses. The pulsatile secretion of ACTH and alpha MSH was maintained despite plasma CRF levels in excess of 400 pmol/liter, and the timing of concentration changes in AVP and ACTH continued to be highly correlated. It is concluded that pulsatile ACTH secretion continues during cortisol, oCRF, or AVP administration. Like that of ACTH, alpha MSH secretion is stimulated by oCRF and AVP administration and suppressed by cortisol. Although the timing of concentration changes in ACTH and alpha MSH is highly correlated, the correlation of the actual concentrations of these two hormones varies considerably in different animals.

Adrenocorticotropic Hormone↗

PubMed1978

Prolonged negative feedback suppression after estradiol administration: proposed mechanism of eugonadal secondary amenorrhea.

The finding of normal gonadotropin and estradiol levels in eugonadal women with secondary amenorrhea suggests a disordered feedback relationship of the hypothalamic-pituitary-ovarian axis. To identify possible defects in negative and positive feedback, we compared the effects of five daily injections of 17 beta-estradiol (E2) in 13 normal women and 11 eugonadal patients with absent cyclic menses. The suppression phase of negative feedback was normal, as LH and FSH were similarly lowered in both groups on day 3. Continued LH (P less than 0.01) and FSH (P less than 0.02) inhibition on day 10 of the protocol, 5 days after the last E2 injection, indicated a defect in the recovery phase of negative feedback in the 11 amenorrheic women. In the 4 patients studied gonadotropin suppression persisted for 3 weeks, E2 did not blunt pituitary responsiveness to GnRH in the amenorrheic women, suggesting a central nervous system site for prolonged gonadotropin inhibition. Nine normal but only 2 amenorrheic women X2 = 4.15; P less than 0.05) exhibited a positive feedback increase in LH on days 4-6. We propose that a defect in the recovery phase of negative feedback to E2 rather than absent positive feedback may be the dominant physiological abnormality which causes secondary amenorrhea by preventing early follicular phase gonadotropin increments and follicular maturation.

Adult↗

PubMed1982

A comparison of subcutaneous and intramuscular administration of human growth hormone in the therapy of growth hormone deficiency.

The sc and im administration of human GH (hGH) was compared in the therapy of GH deficiency. The peak and integrated concentrations of hGH in the plasma of the patients were similar after sc and im injection of an initial dose (0.1 U/kg) of hGH. The peak hGH concentration occurred at 2 h in both groups. The posttreatment height velocity and the change in height velocity at 3-month intervals were also similar in the im and sc groups. The somatomedin generation test resulted in a higher mean peak of somatomedin C after sc injection; however, if the individual peaks of somatomedin C were averaged, there was no difference between sc and im injection. A cross-over at 9 months of therapy to determine patient acceptance of im vs. sc injections indicated overwhelming acceptance of the sc route. The antibody responses to hGH were similar in both groups. We conclude that sc injection of hGH is an effective and safe mode of therapy for GH deficiency. The lipoatrophy that occurred infrequently at the injection site can be eliminated by rotation of sites. Subcutaneous administration of hGH will be more acceptable by the patients with less pain and less noncompliance.

Adolescent↗

PubMed1990

Specific induction of fibronectin gene in rat liver by thyroid hormone.

The regulation of fibronectin (FN) gene expression by thyroid hormone was studied. Rats were rendered hypothyroid by thyroidectomy, and the administration of T4 or T3 was used to produce rats in various thyroid states. RNA was extracted from fresh liver, kidney, and heart, and FN mRNA was determined by dot blot hybridization with a 32P-labeled rat FN cDNA probe. The specificity of the hybridization was assessed by Northern blot analysis. In liver, thyroidectomy decreased the abundance of FN mRNA by half, and daily administration of physiological doses of T4 or T3 for 5-6 days restored FN mRNA to the control level. The administration of pharmacological doses of thyroid hormones induced a further increase in the abundance of FN mRNA. A significant dose-dependent correlation between serum levels of T4 and the abundance of FN mRNA was observed in liver. A receptor-saturating dose of T3 (200 micrograms) given to thyroidectomized rats produced a significant increase in FN mRNA within 6 h after injection, indicating that expression of the FN gene was induced relatively rapidly. Moreover, a nuclear run-off assay revealed that thyroid hormone induces expression of the FN gene at least in part at a transcriptional level. The amount of FN mRNA was also determined in kidney and heart of the same rats. Although the abundance of FN mRNA changed by thyroidectomy or the administration of thyroid hormone in those organs, the magnitude of changes were slight compared with those observed in liver. These results suggested that a marked and dose-dependent induction of the FN gene by thyroid hormone occurs specifically in liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗