Altered keratin biosynthesis follows inhibition of scale morphogenesis by hydrocortisone

Hydrocortisone, administered onto the chorioallantoic membrane (CAM) of 7- to 10-day-old chick embryos, inhibits scale development, in a dose- and stage-dependent manner. The response is also region specific in that hydrocortisone treatment, at a specific dose and time, will completely block scutellate and interstitial scale development while leaving other scale types unaffected. Using histological, biochemical, and immunofluorescence techniques, we have shown that inhibition of scutellate scale morphogenesis prevents the subsequent formation of a beta stratum and alters expression of the alpha keratins. These data support the hypotheses that each avian scale type has its own distinctive temporal, morphological, and biochemical pattern of development; and in the case of scutellate scale development, hydrocortisone treatment alters keratin biosynthesis by interfering with earlier steps in morphogenesis.     

Hydrocortisone inhibits rat basophilic leukemia cell mediator release induced by neutrophil-derived histamine releasing activity as well as by anti-IgE.

We determined the ability of hydrocortisone to inhibit rat basophilic leukemia cell mediator release induced by anti-IgE and by neutrophil-derived histamine-releasing activity (HRA-N). Serotonin release induced by HRA-N and anti-IgE was inhibited by 78 +/- 5 and 70 +/- 4%, respectively (IC50 7.5 x 10(-7)M) by hydrocortisone (10(-5)M). HRA-N does not cause arachidonic acid metabolism, however, anti-IgE induced the generation of PGD2 and leukotriene (LT)C4, and the generation of both mediators was inhibited by 10(-5)M hydrocortisone (IC50 = 4.8 x 10(-7)M, and 3.6 x 10(-9)M, respectively). Inhibition required at least 5 to 6 h of hydrocortisone exposure and was maximal after 22 h. The observed effects of hydrocortisone could be reproduced by human recombinant lipocortin-I (5 x 10(-7)M). Hydrocortisone, 10(-5)M, was a less potent inhibitor of calcium ionophore A23187-mediated serotonin release and PGD2 and LTC4 generation (inhibition of 20 +/- 2, 17 +/- 10, and 37 +/- 10%, respectively). Inasmuch as A23187-induced stimulation is not dependent on receptor coupling, the enhanced ability of hydrocortisone to inhibit IgE- and HRA-N-mediated events as compared with A23187 suggests that one possible site of action of hydrocortisone may be interruption of receptor-effector signals. In the presence of arachidonic acid, hydrocortisone-treated cells released as much LTB4 and PGD2 as control cells, however, serotonin release and LTC4 generation were inhibited 50 and 55%, respectively. Thus, these data suggest that hydrocortisone has three possible sites of action: 1) inhibition of phospholipase A2 activity, 2) inhibition of glutathione-s-transferase, and 3) inhibition of serotonin release by a third mechanism, possibly by interrupting the coupling of receptor and effector systems.     

Stimulation by glucocorticoids of the differentiated phenotype of chondrocytes and the proliferation of rabbit costal chondrocytes in culture

Hydrocortisone stimulated glycosaminoglycan (GAG) synthesis, a characteristic of the cartilage phenotype, of rabbit costal chondrocytes in confluent quiescent culture, as judged by the incorporations of [35S]sulfate and [3H]glucosamine. Hydrocortisone also stimulated incorporation of [3H]serine into proteoglycan. The stimulation of GAG synthesis by hydrocortisone was dose-dependent and maximal at a physiological concentration of 10(-7) M. Hydrocortisone also stimulated GAG synthesis in cultures in the log-phase of growth. In this case, its maximal effect was observed at a concentration of 10(-6) M. The magnitude of the increase of GAG synthesis in response to hydrocortisone was larger in confluent culture than in log-phase cultures. Hydrocortisone stimulated DNA synthesis dose-dependently, and its effect was observable at a physiological concentration. However, no stimulation of DNA synthesis by hydrocortisone was observed in serum-free medium, in contrast to that of GAG synthesis. Hydrocortisone also increased protein synthesis and the cell number. Dexamethasone also stimulated the syntheses of both GAG and DNA. These results show that glucocorticoids stimulated both the differentiated phenotype of chondrocytes and the proliferation of rabbit costal chondrocytes in culture. Moreover, the effect of glucocorticoids was primarily on the differentiated phenotype of chondrocytes and its effect on proliferation was permissive.     

Biochemical Aspects of Chick Embryo Retina Development: The Effects of Glucocorticoids

In chick embryo retina during development, DNA synthesis and the activities of DNA polymerase, thymidine kinase, thymidylate synthetase, and ornithine decarboxylase (ODC) declined in parallel from day 7 to 12. The administration in ovo of hydrocortisone reduced significantly, particularly at 8-10 days of incubation, both DNA synthesis and the four enzyme activities tested. The effect was dose dependent, reaching the maximum with 50-100 nmol of hydrocortisone, 8-16 h after treatment. The highest inhibition was found for ODC activity (70%), followed by thymidine kinase activity (62%) and DNA synthesis (45%), whereas activities of DNA polymerase and thymidylate synthetase were reduced only by 30%. The inhibitory effect was exerted by all the glucocorticoids tested, with dexamethasone and hydrocortisone being the most efficacious. The results support the view that glucocorticoids reduce the proliferative events in chick embryo retina, particularly at 8-10 days of embryonic life.     

Hydrocortisone induces an increase of amylase content in individual zymogen granules from rat pancreas

This study was performed to evaluate the effects of different doses of hydrocortisone (1, 10 and 25 mg/kg/day) administered for 1, 3 and 8 days on pancreatic enzyme storage in rats. The enzyme content in both pancreas homogenates and in individual isolated zymogen granules (ZGs) was measured using standard biochemical assays and flow cytometry, respectively. Hydrocortisone did not alter the total amount of pancreatic DNA but increased the pancreas enzyme content in a time-dose-dependent way. Amylase activity was significantly increased after hydrocortisone administration at day +8 when 10 mg/kg/day was used, and from the first day of treatment when 25 mg/kg/day was administered. A significant increase in trypsin activity was also observed in response to 25 mg/kg/day of hydrocortisone but only from the third day of treatment onwards. As compared with control rats, chronic administration of either 1 or 10 mg/kg/day of hydrocortisone did not alter significantly either the size or the percentage of the two ZG subpopulations (Z1 and Z2) identified in the pancreas by flow cytometry; in addition, no significant changes were observed in the mean amylase content per individual granule, although its mean concentration increased in rats treated with 10 mg/kg/day for 3 and 8 days. Nevertheless, when 25 mg/kg/day of hydrocortisone were administered for 1 and 3 days, a significant increase in the proportion of Z1 ZGs was observed, which may be related to the formation of new and smaller ZGs. When a very high dose of hydrocortisone (25 mg/kg/day) was used, an overall increase in the pancreatic enzyme content related to an increase in the mean amylase content per individual ZG was observed; this effect was apparent from the first day of treatment in the Z1 subset of ZGs and from day +3 in the Z2 subpopulation. Only a high concentration of hydrocortisone was able to alter the enzyme storage process in individual zymogen granules, but they maintain a normal enzyme load at lower hydrocortisone doses.     

Comparative study of the effect of hydrocortisone and thyroxine on suckling mouse small intestine in organ culture

The influence of hydrocortisone (10(-8)--10(-5) M) and thyroxine (10 (-9)--10(-6) M) on intestinal epithelial cell differentiation and proliferation have been studied using explants of suckling mouse jejunum maintained in serum-free organ culture. Hydrocortisone induced the appearance of sucrase activity and increased trehalase, glucoamylase, lactase and alkaline phosphatase activities. Thyroxine was completely ineffective at all the concentrations used. None of these hormones affected the mitotic activity or the 3H-thymidine incorporation into DNA. These results demonstrate that hydrocortisone but not thyroxine acts directly on intestinal brush border membrane differentiation and that both hormones do not influence the proliferation of the epithelial cells during postnatal development.     

Distinctive effects of hydrocortisone on the modulation of EGF binding and cell growth in hela cells grown in defined medium

Hydrocortisone modulates the binding capacity of HeLa cells for ¹²⁵I-labeled epidermal growth factor (EGF). A twofold increase in ¹²⁵I-labeled EGF binding is observed within 24 hours after the addition of pharmacological concentration of hydrocortisone (5 × 10^?8?1 × 10^?6 M). This enhancement of binding is reversible, and occurs when the cells are cultured in either serum-supplemented or completely defined, serum-free, hormone-supplemented medium. Scatchard analysis of the binding data indicates that the number of ¹²⁵I-EGF binding sites is increased, and that no appreciable change in the affinity of the EGF receptor for labeled EGF occurs. In the serum-free condition hydrocortisone stimulates the growth of HeLa cells, but we have observed no connection between this growth stimulation and the enhancement of EGF binding. The growth response to hydrocortisone is independent of EGF, and the concentration dependency of the growth response to EGF is unaltered by the addition of hydrocortisone to the medium. Hydrocortisone elicits the growth response at a concentration as low as 5 × 10^?9 M, while a concentration higher than 5 × 10^?8 M is required to affect the binding capacity for ¹²⁵I-EGF. These effects are specific for glucocorticoid steroids. Similar concentrations of progesterone, testosterone, or estradiol produce no measurable response. Although the elevation of EGF receptor levels in the serum-supplemented medium is similar to that observed in the serum-free cultures, hydrocortisone is growth-inhibitory under these conditions. This growth inhibition occurs at pharmacological concentrations of hydrocortisone with a concentration dependency that is similar to that of the EGF receptor modulation.     

Endocrine Regulation of Fetal Adipose Tissue Metabolism in the Pig: Role of Hydrocortisone

Glucocorticoids have been shown to be essential for the excessive fat deposition and development of obesity in several animal models. This study was performed to characterize the role of glucocorticoids in the developmental regulation of adipose tissue metabolism. On day 70 of gestation, pig fetuses were hypophysectomized by micro-cauterization. Hypophysectomized fetuses were implanted subcutaneously with hydrocortisone pellets or received no hormone replacement. Fetuses were removed by laparotomy on day 90 of gestation. Additional fetuses were hypophysectomized on day 70, implanted with hydrocortisone pellets on day 90 and removed on day 105 of gestation. Several intact fetuses were also implanted subcutaneously with hydrocortisone pellets during this later gestational period. Serum cortisol concentrations were reduced in hypophysectomized pigs at both fetal ages and were restored to intact levels by hydrocortisone treatment. Hydrocortisone supplementation enhanced lipolytic response to isoproterenol in intact fetuses but failed to restore lipolytic response to isoproterenol in hypophysectomized animals at either fetal age. Hydrocortisone induced a slight increase in lipogenesis in hypophysectomized fetuses when administered from 70 to 90 days of gestation and a more dramatic increase when administered from days 90 to 105 of gestation. However, hydrocortisone had no effect on basal or insulin stimulated lipogenesis in intact fetuses when administered from days 90 to 105 of gestation. These results indicate that hydrocortisone may have a primary influence on adipose tissue metabolism during late fetal development only in the absence of inhibition from counterregulatory hormones of pituitary origin.     

Review: cornification,morphogenesis and evolution of feathers

Feathers are corneous microramifications of variable complexity derived from the morphogenesis of barb ridges. Histological and ultrastructural analyses on developing and regenerating feathers clarify the three-dimensional organization of cells in barb ridges. Feather cells derive from folds of the embryonic epithelium of feather germs from which barb/barbule cells and supportive cells organize in a branching structure. The following degeneration of supportive cells allows the separation of barbule cells which are made of corneous beta-proteins and of lower amounts of intermediate filament (IF)(alpha) keratins, histidine-rich proteins, and corneous proteins of the epidermal differentiation complex. The specific protein association gives rise to a corneous material with specific biomechanic properties in barbules, rami, rachis, or calamus. During the evolution of different feather types, a large expansion of the genome coding for corneous feather beta-proteins occurred and formed 3–4-nm-thick filaments through a different mechanism from that of 8–10 nm IF keratins. In the chick, over 130 genes mainly localized in chromosomes 27 and 25 encode feather corneous beta-proteins of 10–12 kDa containing 97–105 amino acids. About 35 genes localized in chromosome 25 code for scale proteins (14–16 kDa made of 122–146 amino acids), claws and beak proteins (14–17 kDa proteins of 134–164 amino acids). Feather morphogenesis is periodically re-activated to produce replacement feathers, and multiple feather types can result from the interactions of epidermal and dermal tissues. The review shows schematic models explaining the translation of the morphogenesis of barb ridges present in the follicle into the three-dimensional shape of the main types of branched or un-branched feathers such as plumulaceous, pennaceous, filoplumes, and bristles. The temporal pattern of formation of barb ridges in different feather types and the molecular control from the dermal papilla through signaling molecules are poorly known. The evolution and diversification of the process of morphogenesis of barb ridges and patterns of their formation within feathers follicle allowed the origin and diversification of numerous types of feathers, including the asymmetric planar feathers for flight.     

Anti-inflammatory drugs, prostanoid and proteoglycan production by cultured bovine articular chondrocytes

The effect of various anti-inflammatory drugs on the production of prostaglandins E2 and F2 alpha, 6 keto PGF1 alpha and thromboxane B2 by bovine articular chondrocytes was measured by radioimmunoassay. While indomethacin and meclofenamic acid caused a dose-dependent inhibition of all prostanoids measured, the effects of hydrocortisone and colchicine varied with respect to different prostanoids. Hydrocortisone (10(-7)M - 10(-13)M) both in the presence and absence of added arachidonic acid, resulted in an inhibition of prostaglandins E2 and F2 alpha, and to a lesser extent, 6 keto PGF 1 alpha, but TxB2 production was only slightly inhibited by the drug in the absence of arachidonic acid and markedly increased in its presence. Colchicine (10(-7)M-10(-3)M) had the opposite effect, causing an inhibition of TxB2 and stimulating PGE2 and 6 keto PGF1 alpha production. These findings suggest that certain anti-inflammatory drugs may, in addition to their action on phospholipase A2 and cyclo-oxygenases, exert potent effects at the level of the different synthetases. In order to see whether these alterations in relative prostanoid levels affected proteoglycan metabolism, the effect of anti-inflammatory drugs on proteoglycan synthesis by cultured chondrocytes was tested using 35SO4 labeling methodology. The results showed that at the concentrations tested (10(-5)M to 10(-7)M), indomethacin, dexamethasone, hydrocortisone and colchicine inhibited 35SO4 incorporation into newly synthesized proteoglycan molecules both in the presence (10(-6)M) and absence of exogenous arachidonic acid. In the same concentration range chloroquine had no effect. These results do not support the hypothesis of direct prostanoid involvement in the modulation of proteoglycan synthesis in articular cartilage.     

Hydrocortisone and progesterone regulation of the proliferation,morphogenesis, and functional differentiation of normal rat mammary epithelial cells in three dimensional primary culture

The mechanisms of action of, and resistance to, the steroidal regulators of normal mammary epithelial and breast cancer cell development are only partially understood. A major obstacle to research progress has been the difficulty in supporting physiologically relevant development of normal mammary epithelial cells (MEC) under defined serum-free conditions. A primary culture system was developed in our laboratory that permits nonfunctional rat MEC to undergo extensive proliferation, functional differentiation, as well as multilobular and lobuloductal branching alveolar morphogenesis. In the studies reported here, the contributions of hydrocortisone and progesterone during the coordinate induction of cellular proliferation, organoid morphogenesis, and functional capacity were assessed. Hydrocortisone (0.1–10 μg/ml) induced alveolar and multilobular branching morphogenesis, suppressed lobuloductal branching morphogenesis, and enhanced casein accumulation. Hydrocortisone also played a role in maintaining alveolar as well as multilobular branching morphogenesis and casein levels. Progesterone (0.01–1 μg/ml) induced cellular proliferation as well as multilobular and lobuloductal branching morphogenesis, and suppressed casein accumulation. At a supraphysiological concentration (10 μg/ml), progesterone inhibited cell growth, alveolar branching morphogenesis, and casein accumulation. MEC cultured without progesterone for up to 1 week retained the ability to respond when subsequently exposed to this steroid. Reversibility studies suggested that progesterone was required for the induction, but not the maintenance of the mitogenic, morphogenic, and lactogenic effects. This physiologically relevant primary culture system can be used to study the factors that regulate steroid responsiveness as well as the cross-talk between steroid and growth factor receptor signaling pathways in normal MEC and breast cancer cells. © 1995 Wiley-Liss, Inc.     

How and when the regional competence of chick epidermis is established: feathers vs. scutate and reticulate scales, a problem en route to a solution

Most of the chick body is covered with feathers, while the tarsometatarsus and the dorsal face of the digits form oblong overlapping scales (scuta) and the plantar face rounded nonoverlapping scales (reticula). Feathers and scuta are made of beta-keratins, while the epidermis of reticula and inter-appendage or apteria (nude regions) express a-keratins. These regional characteristics are determined in skin precursors and require an epidermal FGF-like signal to be expressed. Both the initiation of appendages, their outline and pattern depend on signals from the dermis, while their asymmetry and outgrowth depend on epidermal competence. For example, the plantar dermis of the central foot pad induces reticula in a plantar or feathers in an apteric epidermis, in a hexagonal pattern starting from the medial point. By manipulating Shh levels in the epidermis, the regional appendage type can be changed from scuta or reticula to feather, whereas the inhibition of Wnt7a, together with a downregulation of Shh gives rise to reticula and in extreme cases, apteria. During morphogenesis of plantar skin, the epidermal expression of En-1, acting as a repressor both of Wnt7a and Shh, is linked to the formation of reticula. Finally, in birds, the complex formation of feathers, which can be easily triggered, even in the extra-embryonic somatopleure, may result from a basic genetic program, whereas the simple formation of scales appears secondarily derived, as requiring a partial (scuta) or total (reticula) inhibition of epidermal outgrowth and beta-keratin gene expression, an inhibition lost for the scuta in the case of feathered feet breeds.     

Limb malformations of rat fetuses exposed to a distal inhibitor of cholesterol biosynthesis

Triparanol, an inhibitor of desmosterol Delta24 reductase, produces a high rate of limb malformations in rat fetuses exposed at gestational day 10 (gd 10) to a single oral dose (150-200 mg/kg) given to the pregnant dam. AY9944, another efficient distal inhibitor of cholesterol biosynthesis that blocks dehydrocholesterol Delta7 reductase, produces a similar degree of cholesterol depletion but fewer malformations. Gas liquid chromatography-mass spectrometry (GC-MS) profiling of the sterols in the serum of the dams and in extracted embryos shows that in addition to desmosterol Delta24 reductase inhibition the conversion of Delta8 to Delta7 unsaturated sterols is also blocked by Triparanol. Therefore, the inhibitor induces the accumulation of desmosterol (Delta8 cholesten-3beta-ol, 8-dehydrocholesterol) and zymosterol (Delta8, Delta24 cholestadien-3beta-ol) in embryo tissues. The high concentration of the teratogenic drug assayed in the embryos at three successive gestational days (10-30 micro g/g) is thought to cause the blockade in both Delta24 reductase and Delta8-Delta7 isomerase, which results in the particular profile of aberrant sterols. Comparison of the animal model with human syndromes, including limb osseous and skeleton perturbations, suggests a combination of desmosterol and Delta8 unsaturated sterols as being involved in the deleterious influence on limb bone formation.     

Effects of retinoids on differentiation, lipid metabolism, epidermal growth factor, and low-density lipoprotein binding in squamous carcinoma cells

The relationship among keratinocyte differentiation capacity, lipid synthesis, low-density lipoprotein (LDL) metabolism, plasma membrane composition, and epidermal growth factor (EGF) binding has been studied in SCC-12F2 cells. The differentiation capacity of the cells, i.e., ionophore-induced cornified envelope formation, was inhibited by various retinoids and stimulated by hydrocortisone. Retinoids that caused a significant reduction of cornified envelope formation, i.e., retinoic acid and 13-cis-retinoic acid, caused only minor changes in lipid synthesis and plasma membrane composition. Arotinoid ethylsulfone, having a minor effect on cornified envelope formation, caused a drastic inhibition of cholesterol synthesis, resulting in changes in the plasma membrane composition. Hydrocortisone stimulated cornified envelope formation but had only minor effects on lipid synthesis and plasma membrane composition. Of all retinoids tested, only arotinoid ethylsulfone caused a drastic increase in EGF binding, while hydrocortisone had no effect. Retinoic acid, arotinoid ethylsulfone, and hydrocortisone had no effects on LDL binding and only minor effects on LDL degradation. These results clearly demonstrate that the plasma membrane composition is not related to keratinocyte differentiation capacity, but most likely does determine EGF binding. Furthermore, EGF binding does not determine keratinocyte differentiation capacity.     

Hydrocortisone does not affect major platelet receptors in inflammation in vitro

HYPOTHESIS: Platelet function is an important factor for the fate of intensive care patients. Several factors may influence this function. Recently, it was demonstrated that hydrocortisone has immunologic effects in septic shock and therefore may affect cell adhesion molecules. The aim of the present study was to examine effects of hydrocortisone on platelet receptor expression in healthy individuals and septic patients in vitro. METHODS: Citrated blood samples were drawn from 10 healthy volunteers and 10 septic patients. Samples were adjusted with hydrocortisone to final concentrations of 4.5 microg mL(-1), 9.0 microg mL(-1) (sepsis-equivalent bolus) and 90 microg mL(-1), respectively. A control group received no additional hydrocortisone. Expression of CD62P, CD41, PAC-1 and CD42b on the surface of resting or agonist-stimulated platelets was determined by whole blood flow cytometry using fluorescence-labeled monoclonal antibodies. RESULTS: Hydrocortisone had no significant influence on the expression of CD62P, CD41 and PAC-1. After administration of 90 microg mL(-1) hydrocortisone the expression of CD42b was decreased compared to controls after activation. Differences between volunteers and sepsis patients were found for all receptors after activation. CONCLUSIONS: Hydrocortisone mediates immunmodulating effects in therapy of patients suffering of septic shock without involvement of specific platelet receptors in vitro.     

Inhibition of histone deacetylase activity on specific embryonic tissues as a new mechanism for teratogenicity

BACKGROUND: the inhibition of histone deacetylase (HDAC) has been reported as an effective mechanism on therapy in neoplastic diseases. Among HDAC inhibitors, Trichostatin A (TSA) and Valproic Acid (VPA) prevent the tumorigenesis in rodent and human models. Malformations as neural tube and axial skeletal defects are well-known VPA side effects. Recent hypotheses suggest the HDAC inhibitor activity as the teratogenic mechanism of VPA. The teratogenic potency of TSA is, at the moment, unknown. The aim of the present work is to investigate the HDAC inhibition on embryos exposed in utero to TSA or VPA and to compare the teratogenic potential of these two molecules on the axial skeleton morphogenesis. METHODS: Pregnant CD mice were i.p. treated on day 8 post coitum (9.00 a.m.) with 400 mg/kg VPA or with 0, 2, 4, 8, 16 mg/kg TSA. Embryos explanted 1 hr after the treatment from some females exposed to 400 mg/kg VPA or to 16 mg/kg TSA were processed for Western blotting and immunohistochemical analysis, in order to evaluate the histone hyperacetylation in the total embryo homogenates and to visualize the hyperacetylated tissues. Foetuses at term were processed for skeletal examination. RESULTS: Both VPA and TSA were able to induce hyperacetylation on embryos, specifically at the level of the caudal neural tube and of somites. At term, TSA showed teratogenic effects at the axial skeleton, quite similar to those observed after VPA exposure. CONCLUSIONS: In conclusion, both VPA and TSA are teratogenic in mice. A direct correlation between somite hyperacetylation and axial abnormalities could suggest the HDAC inhibition as the mechanism of the teratogenic effects.     

Influence of hydrocortisone acetate on pancreas and mucosal weight, amylase and disaccharidase activities in 14-day-old pigs.

1. One litter of 12 pigs was used to evaluate the effects of hydrocortisone acetate injection on organ weight and carbohydrase activities. 2. Pigs were injected with hydrocortisone acetate or an equal volume of saline at 7 days of age and killed at 14 days, and tissues were collected, weighted, and analyzed for carbohydrase activities. 3. Hydrocortisone had no effect (P greater than 0.40) on daily gain, liver weight, spleen weight, or small intestinal length. 4. Hydrocortisone increased pancreatic weight by 29% and total pancreatic alpha-amylase content by 38%. 5. Hydrocortisone increased duodenal mucosal weight by 23%, duodenal lactase activity by 44%, duodenal maltase activity by 163%, and duodenal sucrase activity by 214%.     

Mouse fetal kidneys in serum-free organ culture: effects of epidermal growth factor and hydrocortisone.

1. The present study was undertaken to determine whether epidermal growth factor (EGF, 100 ng/ml) or hydrocortisone (HC, 10(-8)-10(-5) M) directly influence proliferation and differentiation of mouse fetal kidney maturing in serum-free organ culture. 2. Addition of EGF to the medium significantly stimulated DNA synthesis after 2 and 5 days of culture. Labelled nuclei were mainly localized in the mesenchymal tissue. Protein synthesis remained unchanged. Activities of three hydrolases, markers of brush border differentiation, were reduced. 3. Hydrocortisone (HC), at all concentrations used, significantly inhibited DNA synthesis. Labelled nuclei were distributed in various cell populations of both control and treated explants. Protein synthesis was stimulated by 10(-7) M after 5 days of culture. Hydrolase activities were slightly modified by HC treatment. 4. The present results indicate that EGF stimulates whereas HC decreases proliferation. Both factors have regulatory effects on brush border maturation. 5. Thus, this culture model is a valuable tool for the study of nephrogenesis.     

Activation of human B lymphocytes. IV. Regulatory effects of corticosteroids on the triggering signal in the plaque-forming cell response of human peripheral blood B lymphocytes to polyclonal activation.

In vitro hydrocortisone in physiologic and pharmacologically attainable concentrations caused a marked enhancement of the PWM-induced PFC response of normal human peripheral blood B lymphocytes. This effect was seen only when hydrocortisone was added within the first 24 hr of culture and only when hydrocortisone and PWM were present together in cultures. Only suprapharmacologic concentrations of hydrocortisone (10(-3) M) were capable of suppressing early B cell activation. Late stages of antibody production and secretion were resistant to suppression by even these extraordinarily high concentrations. Hydrocortisone did not replace the T cell requirement of PWM-induced PFC responses. A single dose of in vivo hydrocortisone (400 mg) to normal adult volunteers did not produce this enhancing effect when PFC responses were measured in vitro in the absence of hydrocortisone. The data strongly suggest that the enhancing effect of hydrocortisone was due not to elimination of naturally occurring suppressor cells, but to a modulation of the triggering signal either directly on the B cell itself or via the balance of positive and negative T cell regulation of B cell activation.     

Effect of hydrocortisone on the growth and development of larvae Tenebrio molitor

Hydrocortisone administered with the food causes inhibition of growth in larvae Tenebrio molitor. Hydrocortisone together with the reduction in the rate of growth retards the moulting cycle in larvae T. molitor. The action of hydrocortisone does not influence greatly the number of larvae moulting cycles.