Acute renal failure in dense deposit disease: complete recovery after combination therapy with immunosuppressant and plasma exchange.

We describe the clinical course of a female adolescent who was followed because of isolated microhematuria and hypocomplementemia before admission to hospital with a sudden onset of acute renal failure. At presentation, she exhibited complement consumption through the complement alternative pathway (AP) while other serologic tests were negative. Renal biopsy revealed dense deposit disease (DDD) with a crescentic pattern. Intravenous methylprednisolone, followed by plasma exchange (PE), and intravenous cyclophosphamide pulses were started shortly after admission. C3NeF and anti-factor H antibody tests were negative. Serum factor H and I levels were normal as well as factor H activity. Screening for mutation in the factor H gene revealed the H402 allele variant. Clinical remission, defined as normalization in renal function and in the activity levels of the complement AP, was noted at one month post-presentation and throughout the follow-up. A repeat renal biopsy showed the disappearance of crescent formation, whereas electron microscopy revealed no regression in dense transformation of the lamina densa. In summary, our patient was successfully treated with immunosuppressant and PE. The absence of known factors associated with DDD suggests that, in this particular case, other regulatory mechanisms of complement AP might have been involved in the disease process.

IGFBP-1 levels in adult women born small for gestational age suggest insulin resistance in spite of normal BMI.

OBJECTIVE: Impaired fetal development may contribute to decreased insulin sensitivity. This study was designed to characterize serum markers of insulin resistance in adults born small for date or born prematurely. STUDY DESIGN: Fifty subjects, all women, were evaluated at a mean age +/- SD of 26 +/- 2 years (range: 23-30 years). They were allocated to three groups: (i) born fullterm with birth weight <2600 g (n = 18) (small for gestational age, SGA), (ii) born before gestational week 32 (n = 15) (ex-preterm), and (iii) controls, born fullterm with appropriate birth weight (n = 17). Anthropometric data as well as fasting serum samples of plasma B-glucose, serum lipids, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) levels were determined. RESULTS: In the SGA group final height was lower and they weighed less compared with the controls. Fasting insulin and glucose levels did not differ amongst the groups. Triglycerides were lower in the SGA group and in the ex-preterm group compared with the controls (P < 0.05). The SGA group showed lower IGFBP-1 levels compared with the controls median 17 (range 3-121) vs. 26 (7-67) microg L-1; P < 0.05]. The IGF-I levels in the SGA, ex-preterm and control groups were 212 +/- 58, 259 +/- 37 and 216 +/- 32 microg L-1, respectively, corresponding to a mean SD score of -0.8 +/- 1.0, 0.1 +/- 0.6 and -0.6 +/- 0.6. CONCLUSION: As IGFBP-1 is a marker of insulin sensitivity, the low levels observed in adult women with normal BMI, born small for date, suggest relative insulin resistance in spite of normal BMI.

Regulation of K+ transport in the rat distal colon via angiotensin II subtype receptors and K+ -pathways.

The role of angiotensin subtype-1 (AT1) and -2 (AT2) receptors in mediating the effects of angiotensin II (ANG II) on several K+ transporters was studied in rat distal colon using an Ussing chamber. Angiotensin II induced K+ secretion at two different doses. Secretion occurred at 10-(8) and 10-(4) M, as a result of an increase in serosal-to-mucosal flux (Js-m). The ANG II-induced stimulation of Js-m at a low dose (10-(8) M) was abolished by PD123319 while losartan did not alter the low-dose ANG II-dependent increase in Js-m. In contrast, the increase in Js-m induced by a high-dose of ANG II (10-(4) M) was blocked by losartan, whereas PD123319 partially reduced the stimulatory effect. In the presence of both blockers, high-dose ANG II induced an inhibition of basal Js-m. Low-dose ANG II activated the barium-sensitive K+ channels, whereas the Na+, K+, 2Cl- cotransporter and the Na+, K+ -ATPase pump were unchanged. At the high dose, ANG II activated the barium-sensitive K+ channels and the Na+, K+, 2Cl- cotransporter and inhibited the Na+, K+ -ATPase pump. These data indicate that ANG II stimulates serosal-to-mucosal K+ flux in the rat distal colon at high and low doses via different receptors and K+ transporters.

Antenatal glucocorticoids and renal function after birth.

Antenatal glucocorticoid treatment is widely used in cases of threatening preterm delivery. Both human and animal studies have confirmed that glucocorticoids promote pulmonary maturation in fetuses. Several studies indicate that prenatal glucocorticoids also stimulate renal maturation. Although the current knowledge about the effects of glucocorticoids on kidney function is mainly concentrated on short-term effects, there are animal studies suggesting that antenatal glucocorticoid treatment may also cause permanent changes in kidney morphology and renal function. It still remains to be investigated if antenatal glucocorticoid treatment induces long-term effects in humans.

Prenatal exposure to high levels of glucocorticoids increases the susceptibility of cerebellar granule cells to oxidative stress-induced cell death.

There is growing concern that prenatal exposure to excessive glucocorticoids may have deleterious effects on the development of various organs, including the nervous system. This study aimed at evaluating whether prenatal exposure to high levels of glucocorticoids might produce long-term effects on neuronal cell survival. Pregnant rats were injected i.p. with 0.1 mg/kg dexamethasone (DEX) from day 14 postconception, and cerebellar granule cells (CGC) were prepared from 1-week-old rats from DEX-treated and control dams. After 7 days in culture, cells were exposed to H(2)O(2), methylmercury, or colchicine at concentrations known to induce apoptotic cell death. After exposure to H(2)O(2) or methylmercury, both inducing oxidative stress, the number of apoptotic cells was significantly higher in DEX- than in control-CGC. Because mitochondria play a key role in apoptosis, mitochondrial function was investigated, and a decrease in the threshold level of Ca(2+) necessary for induction of mitochondrial permeability transition, in Ca(2+) accumulation rate, and in oxygen consumption was detected in DEX-CGC. Moreover, the activity of the antioxidant enzyme catalase was significantly decreased in DEX-CGC. A similar decrease in catalase activity was observed in cerebellar homogenate from newborn and 40-day-old DEX-rats. In conclusion, these results indicate that prenatal exposure to high levels of glucocorticoids induces long-lasting changes in CGC rendering them more sensitive to oxidative stress. With the increasing use of multiple doses of glucocorticoids in preterm infants, the possibility that prenatal exposure to excess glucocorticoids may lead to long-term neurological consequences becomes a relevant issue.

Alpha-haemolysin of uropathogenic E. coli induces Ca2+ oscillations in renal epithelial cells.

Pyelonephritis is one of the most common febrile diseases in children. If not treated appropriately, it causes irreversible renal damage and accounts for a large proportion of end stage renal failures. Renal scarring can occur in the absence of inflammatory cells, indicating that bacteria may have a direct signalling effect on renal cells. Intracellular calcium ([Ca2+]i) oscillations can protect cells from the cytotoxic effects of prolonged increases in intracellular calcium. However, no pathophysiologically relevant protein that induces such oscillations has been identified. Here we show that infection by uropathogenic Escherichia coli induces a constant, low-frequency oscillatory [Ca2+]i response in target primary rat renal epithelial cells induced by the secreted RTX (repeats-in-toxin) toxin alpha-haemolysin. The response depends on calcium influx through L-type calcium channels as well as from internal stores gated by inositol triphosphate. Internal calcium oscillations induced by alpha-haemolysin in a renal epithelial cell line stimulated production of cytokines interleukin (IL)-6 and IL-8. Our findings indicate a novel role for alpha-haemolysin in pyelonephritis: as an inducer of an oscillating second messenger response in target cells, which fine-tunes gene expression during the inflammatory response.

Increased blood pressure but normal renal function in adult women born preterm.

UNLABELLED: It has been suggested that children born small for gestational age may develop hypertension and renal dysfunction in adulthood due to impaired fetal kidney development. Very little information on this issue is available on children born preterm. The objective of this study was to investigate the relationship between birth weight, blood pressure, and kidney function in adult subjects who were born preterm or born small for gestational age (SGA). STUDY DESIGN: Subjects (n = 50), all women born between 1966 and 1974, were evaluated at a mean age of 26 +/- 1.9 years. They were allocated to three groups: (1) born before gestational week 32 (n = 15), (2) born full term with birth weight < 2600 g (n = 18) (SGA), and (3) controls, born full term with appropriate birth weight (n = 17). Casual blood pressure, ambulatory 24-h blood pressure (ABPM), glomerular filtration rate (GFR), renal plasma flow (ERPF) and urinary albumin excretion were determined. RESULTS: Preterms had significantly higher casual systolic and mean arterial blood pressure levels compared to controls (123 +/- 13 vs 110 +/- 7 mmHg, P < 0.01, and 87 +/- 9 vs 79 +/- 6 mmHg, P < 0.005, respectively). ABPM was not significantly different between the groups. When the number of systolic recordings > 130 mmHg/subject during ABPM was calculated, the preterms had significantly more recordings above this value (P < 0.05) as well as a significantly increased area under the curve > 130 mmHg and > 140 mmHg systolic (P < 0.05) compared to the controls. SGA subjects were not significantly different from controls. There were no significant differences in GFR, ERPF or urinary albumin excretion between the three groups. CONCLUSION: Women born preterm seem to have a disturbance in blood pressure regulation in adulthood, a finding that is not observed for those born small for gestational age. Kidney function in early adulthood seems to be normal in subjects born preterm or small for gestational age.

Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers.

Leptin has been implicated in the regulation of body weight and energy balance; Leptin is produced by adipocytes and placental tissue. Chronic fetal hyperinsulinemia and accelerated fetal growth with increased amounts of body fat are frequent findings in the offspring of diabetic mothers. In this study, we examined whether leptin levels in cord blood of infants of type 1 diabetic mothers (n = 29), gestational diabetic mothers (n = 6 and controls (n = 96) correlated with level of maternal glucose control, maternal leptin level at delivery, gender, fetal and placental size, and C-peptide in cord blood at birth. Leptin was significantly elevated in infants of type 1 diabetic (24.7 ng/ml) and gestational diabetic mothers (29.3 ng/ml) as compared to controls (7.9 ng/ml). C-peptide was also significantly higher in infants of type 1 diabetic (0.91 nmol/l) and gestational diabetic mothers (0.99 nmol/l) vs controls (0.34 nmol/l). Infants of type 1 diabetic mothers with a leptin level in cord blood above the upper normal range, i.e. > 30 ng/ml (n = 13), had an average maternal HbA1c level of 5.4% (normal < 5.5%) that was not different from 5.2% in infants with a leptin level < 30 ng/ml (n = 15). In both neonatal groups of diabetic mothers, leptin in cord blood did not correlate with maternal leptin concentrations, placental weight, birthweight, gender and cord blood C-peptide. In controls, leptin in cord blood was higher in girls than in boys (p = 0.044) and correlated significantly with birthweight (p = 0.41, p < 0.001) and cord blood C-peptide (p = 0.44, p < 0.001) but not with maternal leptin level or placental weight. The 3-4 times higher leptin levels in the offspring of diabetic mothers than normal could reflect increased adipose tissue mass and/or increased contribution from other sources such as placental tissue.

Nitric oxide inhibits potassium transport in the rat distal colon.

The effect of the nitric oxide (NO) pathway on K+ (measured using 86Rb) transport in adult rat distal colon was investigated in muscle-stripped segments of colons mounted in Ussing chambers. When added to the mucosal solution, the endogenous precursor of NO, L-arginine (30 mM), inhibited both mucosal-to-serosal and serosal-to-mucosal 86Rb fluxes and caused a prolonged decrease of short-circuit current (Isc). This effect was significantly reduced by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) but not by D-NAME. Mucosal application of S-nitroso-N-acetyl-penicillamine (SNAP) inhibited mucosal-to-serosal 86Rb flux without affecting serosal-to-mucosal transport. Serosal addition of two different exogenous NO donors, sodium nitroprusside (0.1 mM) and SNAP (0.2 mM), decreased serosal-to-mucosal 86Rb flux, whereas Isc increased. The SNAP-induced decrease in 86Rb flux was abolished by 1H-(1,2,4)oxodiazolo(4,3-a)quinoxalin-1-one (0.2 mM), a selective inhibitor of NO-stimulated soluble guanylyl cyclase, and by methylene blue (0.01 mM). Addition of 8-bromo-cGMP (2 x 10(-4) M) in the presence of an inhibitor of cGMP-specific phosphodiesterase mimicked the effects of NO-donating compounds. This study provides evidence that NO inhibits K+ transport in the rat distal colon via a cGMP-dependent pathway. The effect on net K+ transport may depend on the side of NO action.

Beta-adrenergic stimulation of cellular K+ uptake in rat distal colon.

We recently demonstrated that the ratio between colonic K+ absorptive and K+ secretive pathways was higher in infant than in adult rats. To test the hypothesis that hormones selectively affect these pathways during ontogeny we examined the effect of adrenergic agonists on cellular K+ uptake in distal colon from infant (10-day-old) and adult (50-day-old) rats. Here we describe that adrenaline (10(-5) M) increased total and ouabain-insensitive 86Rb uptake in both age groups, but it did not affect ouabain-sensitive 86Rb uptake. This stimulation was more pronounced in adult than in infant rats. The effect of adrenaline was mediated via beta-adrenergic receptors. Incubation in vitro with beta-agonist, isoproterenol, stimulated SCH-28080-sensitive, i.e. H+, K(+)-ATPase-dependent, 86Rb uptake in adult but not in infant rats. The threshold dose of beta-agonist was at 10(-7) M, and the maximal activation was observed at 10(-5) M. In vivo inhibition of beta-adrenergic system with propranolol caused a significant decrease in H+, K(+)-ATPase-dependent 86Rb uptake in infant but not in adult colon. In conclusion, this study suggests that the higher colonic K+ absorption in infant rats may be as a result of a selective beta-adrenergic up-regulation leading to stimulation of the apical H+, K(+)-ATPase.

Prenatal dexamethasone causes oligonephronia, sodium retention, and higher blood pressure in the offspring.

Recent reports have shown that low birth weight infants have a higher incidence of adult hypertension. These observations have stimulated a number of studies designed to evaluate the mechanisms of this phenomenon. In this study, fetal growth retardation was induced by treating pregnant rats with dexamethasone. After birth, pups whose mothers were treated with dexamethasone had a lower body and kidney weight and a lower number of glomeruli than control pups. Immunohistochemistry on treated kidneys demonstrated a marked reduction in the number of cells undergoing mitosis in the cortical nephrogenic zone. In the treated group, body and kidney weight normalized by 60 d of age, but blood pressure was significantly higher compared with controls (130+/-4 versus 107+/-1 mm Hg). In addition, GFR was significantly lower, albuminuria was higher, urinary sodium excretion rate and fractional sodium excretion were lower, and sodium tissue content was higher. In contrast, when pregnant rats were treated with a natural glucocorticoid (hydrocortisone) which is metabolized by the placenta, fetal development and adult blood pressure were normal. In conclusion, we found that high levels of maternal glucocorticoids impair renal development and lead to arterial hypertension in offspring. Even though renal mass eventually normalizes, glomerular damage as well as sodium retention occur and these factors may contribute to the development of hypertension.

Potassium homeostasis: ontogenic aspects.

Potassium is the most abundant intracellular cation and plays an important role in a variety of cell functions. Potassium regulation and homeostasis during infancy are, owing to growth and development, different from in later life: infants need to retain more K+ than adults, to avoid growth retardation. Since the K+ requirements are different in infants and in adults, the mechanisms regulating K+ homeostasis also need to be different. This paper includes a review of the literature concerning the regulation of internal and external K+ balances during ontogeny. We examined the role of gastrointestinal tract, kidney and some tissue stores in K+ excretion and distribution during development. We conclude that positive K+ balance in infancy is characterized by higher K+ absorption in gut, lower K+ secretion/excretion in kidney and immaturity of the mechanisms regulating intra/extracellular K+ distribution. Several factors contribute to maintain the positive K+ balance. They include higher expression of absorptive transporters in colon and probably in kidney, lower expression of secretive transporters in colon and kidney, lower renal K+ excretion following K+ loading, immaturity of hepato-renal K+ reflex mechanism, immaturity of tissue K+ binding/releasing capacity and immaturity of the neuro-hormonal control of K+ transport in several organs.

Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements.

Vasopressin plays an essential role for the regulation of water balance by activating the collecting duct-specific water channel, aquaporin-2 (AQP2). Here we present evidence that vasopressin may also act as a long-term, transcriptional regulator of AQP2. The studies were performed on LLC-PK1 cells, which normally express V2 receptor (V2R) and which were transfected with a fragment of the human AQP2 promoter. Activation of the adenylate cyclase-coupled V2R in LLC-PK1 cells induced phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP) responsive element binding protein (CREB) and expression of c-Fos. Binding of these factors to the CRE and AP1 site did, in combination, lead to AQP2 promoter activation. These results establish the role of vasopressin as a regulator of transcription and are the first example of how a message from a highly specific receptor is, via a dual effect of the cAMP signal on CREB and immediate early gene expression, transduced to the transcription of a final target protein with known biological effects.

Glucocorticoids stimulate the maturation of H,K-ATPase in the infant rat stomach.

The development of gastric H,K-ATPase from fetal to adult life was studied in the rat. The alpha and beta H,K-ATPase mRNA abundance, the protein abundance, and the enzyme activity increased postnatally. The sharpest increase in mRNA and enzyme activity was observed in the weaning period. Several intestinal enzymes are known to be stimulated by glucocorticoids at the time of weaning. To study the role of glucocorticoids in the maturation of gastric H,K-ATPase, we treated 10-d-old rats with a single injection of betamethasone. Twenty-four hours after betamethasone injection, the enzyme activity was significantly higher than in the control animals (2.6-fold, p < 0.05). The abundance of catalytic alpha H,K-ATPase protein was also increased (2.5-fold, p < 0.01). The time-dependent effect of betamethasone on alpha H,K-ATPase mRNA was determined from 6 to 24 h after treatment. Glucocorticoids did not significantly alter the mRNA abundance within 18 h. Twenty-four hours after injection, the gastric H,K-ATPase mRNA was significantly increased compared with controls (2.8- and 2.2-fold increase for alpha and beta subunits, respectively, P < 0.01 for both). In conclusion this study indicates that glucocorticoids may regulate the long-term maturation of gastric H,K-ATPase by indirectly stimulating enzyme synthesis.

Ontogeny of K+ transport in rat distal colon.

Infants need to retain more K+ than adults to avoid growth retardation. Since the K+ requirements are different in infants (I) and in adults (A), the mechanisms regulating K+ homeostasis should also be different. The colon plays an important role for the regulation of K+ homeostasis. Colonic K+ transport is bidirectional. In this study we have examined the development of colonic K+ transport with special reference to the contribution of different K(+)-transporting pathways. The net colonic K+ uptake, as determined by in vivo perfusion studies and by 86Rb uptake, was significantly higher in I than in A rats. In both I and A colon, approximately 80% of total 86Rb uptake was dependent on vanadate-sensitive P-type adenosinetriphosphatases (ATPases), but the contribution of these different ATPases changes during development. The activity of colonic Na(+)-K(+)-ATPase, measured as ouabain-sensitive Na(+)-dependent ATP hydrolysis and as 86Rb uptake, was lower in I than in A rats. In contrast, the activity of K(+)-ATPases located in apical membrane and measured as ouabain insensitive and SCH-28080 sensitive, as ouabain-sensitive Na(+)-independent ATP hydrolysis, and as 86Rb uptake was significantly higher in I than in A rats. The ratio between apically located K(+)-ATPases and basolateral Na(+)-K(+)-ATPase activities was almost 3.2-fold higher in I than in A colon. We identified with Northern blot the expression of the colonic H(+)-K(+)-ATPase and the Na(+)-K(+)-ATPase alpha-subunits. The alpha-mRNA expression of both ATPases was significantly higher in I than in A rats. The pH and K+ sensitivity of the ouabain-insensitive, SCH-28080-sensitive K(+)-ATPase was the same in I and A colons. In conclusion, the relative activity of apical K+ absorbing ATPases is higher in the I than in the A colon, which should aid infants in retaining K+.

Development of urinary concentrating capacity: role of aquaporin-2.

The capacity to concentrate urine develops progressively during postnatal life in most mammalian species. Here we have examined whether low expression of the arginine vasopressin (AVP)-activated water channel aquaporin-2 (AQP-2) may be a limiting factor for the concentrating capacity in the infant rats. Urine osmolality in response to 24-h dehydration increased significantly from 10 to 40 days of age. The most rapid increase occurred during the weaning period, i.e., days 15-20. A similar developmental pattern was observed for AQP-2 mRNA levels in the renal medulla. AQP-2 protein levels also increased markedly from day 10 to 40. Immunohistochemistry revealed that AQP-2 was exclusively located in collecting duct principal cells both in infant and adult rats but that the signal was much weaker in infants. To further examine the relationship between urinary concentrating capacity and AQP-2 expression, we treated rats with a single injection of betamethasone, which is known to accelerate maturation in several organs. Twenty-four hours after treatment, there was an increase in urine osmolality, renal medullary AQP-2 mRNA, and AQP-2 protein levels in infant but not in adult rats. A single injection of a specific V2 agonist caused within 6 h significant increase of AQP-2 mRNA in both infant and adult. The expression of the mRNA of three other transporters involved in the concentrating process, medullary Na(+)-K(+)-ATPase alpha-subunit, Na-K-2Cl cotransporter, and epithelial chloride channel also increased during the weaning period and were upregulated by glucocorticoids. We conclude that there is a well-synchronized development of the many of the components that determine the concentrating capacity and that the low expression of AQP-2 is one of the limiting factors for low concentrating capacity in infants.

Protein phosphatase-1 in the kidney: evidence for a role in the regulation of medullary Na(+)-K(+)-ATPase.

Previous studies of hormonal regulation of renal Na(+)-K(+)-ATPase have indicated that the activity of the sodium pump is regulated by phosphorylation-dephosphorylation reactions. Here we report that okadaic acid (OA) and calyculin A (CL-A), inhibitors of protein phosphatase (PP)-1 and PP-2A, inhibited Na(+)-K(+)-ATPase activity in cells from the rat thick ascending limb (TAL) of loop of Henle in a dose-dependent manner. CL-A was 10-fold more potent than OA. On the basis of the inhibitory constant values of CL-A and OA for PP-1 and PP-2A, it is concluded that the tubular effect is mainly due to inhibition of PP-1. In situ hybridization studies with oligonucleotide probes revealed very strong PP-1 alpha and PP-1 gamma 1 mRNA labeling in the outer stripe of the outer medulla, strong labeling in the inner stripe of the outer medulla, and weak labeling in the inner medulla. Very weak labeling was demonstrated in the outer cortex. PP-1 beta mRNA labeling was very strong in the inner stripe of the outer medulla, whereas the outer stripe had weaker labeling, and the inner medulla had weak labeling. PP-1 alpha, PP-1 beta, and PP-1 gamma 1 mRNA were also demonstrated in the transitional epithelium of the ureter. The abundance of the PP-1 alpha and PP-1 gamma isoforms as measured by immunoblotting was very high in tissue from the outer medulla, which also has a high abundance of the endogenous dopamine-regulated PP-1 inhibitor, DARPP-32.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of glucocorticoids and mineralocorticoids on the mRNA expression of colon ion transporters in infant rats.

Several epithelial ion transporters are developmentally regulated in the preweaning period, at the time when the circulating levels of glucocorticoid and mineralocorticoid hormones increase. The specific role of glucocorticoids and mineralocorticoids in the maturation of epithelial ion transport is still disputed. In this study, we investigated the effect of corticosteroids on the mRNA expression of ion transporters in the infant rat colon, a glucocorticoid- and mineralocorticoid-sensitive organ. The expression of the Na,K-ATPase, the H,K-ATPase and the amiloride-sensitive Na+ channel mRNA was investigated in control rats from fetal to adult life. We found that the mRNA of the three transporters is temporarily up-regulated in the preweaning period. Rats were then injected with a single dose of betamethasone or aldosterone at 10 d of age. The main effect was the glucocorticoid stimulation of the Na,K-ATPase mRNA within 6 h (4-fold). Glucocorticoids did not alter H,K-ATPase nor Na+ channel mRNA within 6 h. Aldosterone moderately (1.7-fold) stimulated Na+ channel within 6 h, but dit not alter Na,K-ATPase nor H,K-ATPase mRNA. Twenty-four hours after injection, both glucocorticoids and mineralocorticoids had less pronounced and distinct effects. In tissue with lower aldosterone receptor abundance (renal cortex) or with no aldosterone receptor (stomach), glucocorticoids induce a similarly rapid increases in Na,K-ATPase mRNA (4-fold within 6 h), whereas aldosterone had no effect within 6 h. However, glucocorticoids did not stimulate Na,K-ATPase mRNA in the brain, a tissue rich in glucocorticoid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)