Changes in characteristics of rat adrenal glomerulosa cells under acute and chronic treatment with ACTH

1983 ◽  
Vol 61 (7) ◽  
pp. 538-546 ◽  
Author(s):  
François Legros ◽  
Jean-Guy Lehoux
Keyword(s):  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
High Plasma ◽  
Zona Glomerulosa ◽  
Cell Suspensions ◽  
Duration Of Treatment ◽  
Glomerulosa Cells ◽  
Cessation Of Treatment

Groups of Long Evans rats were treated with 15 IU ACTH/day for 1–9 days and sacrificed at different intervals during and after treatment. Aldosterone and corticosterone plasma levels were increased above control values for the entire duration of treatment and were decreased to control values as early as 3 days posttreatment. The uptake of [125I]angiotensin II ([125I]AII) by adrenocortical glomerulosa cell suspensions was diminished by 71% at day 9 of treatment and this [125I]AII-uptake capacity slowly returned to control values after cessation of treatment (66.0% of control at day +19). The association constants at equilibrium (Ka) for AII receptors were similar in both treated (0.19 × 109 M−1 at day 9) and control (0.12 × 109 M−1) rats, whereas the number of AII-binding sites was lowered in the glomerulosa cells of treated (Nmax = 6 fmol/50 000 cells) compared with control (29 fmol) animals. In vitro cell suspensions from treated rats had, compared with controls, a lowered basal aldosterone and an increased corticosterone output. Addition of ACTH (10−8 M) to these cell suspensions showed no effect on the aldosterone or corticosterone output, whereas a significant stimulation was observed for cells obtained from control animals. Studies on rats treated 9 days and sacrificed 19 days after cessation of treatment demonstrated that the basal aldosterone and corticosterone output from zona glomerulosa cell suspensions was comparable with that of control rats; the steroid output of these cells could be further stimulated in vitro by addition of ACTH. It is concluded that the chronic ACTH treatment produced (i) a loss of AII receptor of adrenal zona glomerulosa cells, a phenomenon that was reversible 3–4 weeks posttreatment; (ii) a decreased capacity of glomerulosa cells to further respond to ACTH stimuli in vitro, suggesting either a loss of ACTH receptor by these cells or a decrease in activity of enzymes responsible for steroidogenesis, or a lack of endogenous precursor; (iii) a diminution of the thickness of the zona glomerulosa accompanied by an enlargement of the zonae fasciculate–reticularis, resulting in high circulating plasma corticosterone. This high plasma corticosterone level might well be the source of the precursor used in vivo by the zona glomerulosa to maintain the observed high plasma aldosterone level, despite the lowered overall steroidogenic capacities of these cells demonstrated by our in vitro studies.

Antiulcerogenic and antisecretory effects of a novel diphenylmethane derivative and antiestrogen binding site ligand

1988 ◽  
Vol 66 (8) ◽  
pp. 1139-1143 ◽  
Author(s):  
Gary B. Glavin ◽  
Lorne J. Brandes
Keyword(s):  
Binding Site ◽  
Gastric Acid ◽  
Stress Ulcer ◽  
Acid Output ◽  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
Gastric Ulcers ◽  
Ulcer Formation

N,N-Diethyl-2-[4-(phenylmethyl)-phenoxy]-ethanamine hydrochloride (DPPE) is a para-diphenylmethane derivative that binds selectively and with high affinity to the microsomal antiestrogen binding site (AEBS). Recent studies with DPPE indicate that AEBS is closely related to a lower affinity non-H1, non-H2 histamine site that may be associated with calcium channels; the DPPE–AEBS site is different from that which verapamil binds, however. DPPE, but not verapamil, demonstrates antiproliferative effects in vitro and is antiestrogenic in vivo. We now show that DPPE profoundly inhibits restraint and cold stress and ethanol-induced gastric ulcer formation, accelerates ulcer healing, attenuates the stress-induced rise in plasma corticosterone level, and significantly reduces basal and H2 agonist (dimaprit)-stimulated and, to a lesser extent, bethanechol-stimulated gastric acid output in conscious rats. A nonulcerogenic but prostaglandin-depleting dose of indomethacin completely blocks the inhibitory effects of DPPE on stress ulcer formation. Conversely, verapamil only slightly attenuates dimaprit-stimulated gastric acid secretion and exacerbates ethanol-induced gastric ulcers; its anti-stress ulcer effects are only partially attenuated by indomethacin. These findings support the likelihood that the site of action of DPPE is different from that of verapamil, and that an effect on prostaglandins may, at least in part, contribute to its antiulcer and apparent cytoprotective effects.

Effect of angiotensin II on aldosterone and its precursor steroid production in adrenal zona glomerulosa cells from heparin-treated rats

1986 ◽  
Vol 111 (2) ◽  
pp. 222-227 ◽  
Author(s):  
K. Uchida ◽  
S. Azukizawa ◽  
N. Imaizumi ◽  
T. Kigoshi ◽  
I. Yamamoto ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Corticosterone Level ◽  
Plasma Renin ◽  
Plasma Corticosterone ◽  
Zona Glomerulosa ◽  
Threshold Dose ◽  
Lower Response ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Zona Glomerulosa Cells

Abstract. To assess the nature of the heparin-induced aldosterone deficiency, we investigated the stimulatory effect of angiotensin II (All) on aldosterone and its precursor steroids in adrenal zona glomerulosa cells from heparin-treated rats compared with those in the cells from vehicle-treated rats. Heparin-treated rats had low plasma aldosterone levels, high plasma renin activity and plasma All levels, and normal plasma corticosterone level 6 weeks after the treatment (1500 IU/kg, twice daily). Basal aldosterone production, when corrected to a uniform number of cells per group, was similar in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to All; an increase by 4 orders of magnitude in the threshold dose for All and a decrease in the maximum All-stimulated level. The maximum All-stimulated levels, but not the basal levels, of pregnenolone, corticosterone and 18-OHB production were low in the cells from heparin-treated rats. ACTH caused a similar stimulatory effect on aldosterone production in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to potassium; an increase by one order of magnitude in the threshold dose for potassium and a decrease in the maximum potassium-stimulated level, presumably because of the glomerulosa hyporesponsivness to AII. These results suggest that our heparin-treated rats have selective impairment of adrenal zona glomerulosa cells,

PITUITARY AND ADRENAL RESPONSIVENESS IN RATS AFTER PROLONGED TREATMENT WITH ACTH

1963 ◽  
Vol 41 (1) ◽  
pp. 1771-1777
Author(s):  
E. Stark ◽  
J. Fachet ◽  
Katherine Mihály
Keyword(s):  
Prolonged Exposure ◽  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
Prolonged Treatment ◽  
Plasma Corticosterone Level ◽  
Operative Trauma ◽  
Corticosterone Secretion ◽  
Adrenal Corticosterone

Prolonged exposure to ACTH considerably increased adrenal responsiveness in the rat both in vivo and in vitro. The last of 5 and 14 daily injections each produced a significantly higher blood corticosterone level than did a single injection. In the presence of ACTH added in vitro, adrenal corticosterone production in animals subjected to prolonged treatment with ACTH significantly exceeded the production per unit of weight and unit of time measured in saline-treated animals. Reduced adrenal responsiveness in the stage of resistance, elicited by formalin as a non-specific stress, cannot be invoked as an explanation for the absence of an increase in corticosterone secretion. The conclusion is that after prolonged exposure to non-specific stress there is no longer any ACTH hypersecretion.Twenty-four hours after the last injection of prolonged ACTH treatment there was inhibition of endogenous ACTH release by the pituitary gland, formalin produced no rise in the corticosterone level of the peripheral blood, and operative trauma caused substantially less ascorbic acid depletion than it did in saline-treated controls, although the plasma corticosterone level was normal or below normal.

PITUITARY AND ADRENAL RESPONSIVENESS IN RATS AFTER PROLONGED TREATMENT WITH ACTH

1963 ◽  
Vol 41 (8) ◽  
pp. 1771-1777 ◽  
Author(s):  
E. Stark ◽  
J. Fachet ◽  
Katherine Mihály
Keyword(s):  
Prolonged Exposure ◽  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
Prolonged Treatment ◽  
Plasma Corticosterone Level ◽  
Operative Trauma ◽  
Corticosterone Secretion ◽  
Adrenal Corticosterone

Prolonged exposure to ACTH considerably increased adrenal responsiveness in the rat both in vivo and in vitro. The last of 5 and 14 daily injections each produced a significantly higher blood corticosterone level than did a single injection. In the presence of ACTH added in vitro, adrenal corticosterone production in animals subjected to prolonged treatment with ACTH significantly exceeded the production per unit of weight and unit of time measured in saline-treated animals. Reduced adrenal responsiveness in the stage of resistance, elicited by formalin as a non-specific stress, cannot be invoked as an explanation for the absence of an increase in corticosterone secretion. The conclusion is that after prolonged exposure to non-specific stress there is no longer any ACTH hypersecretion.Twenty-four hours after the last injection of prolonged ACTH treatment there was inhibition of endogenous ACTH release by the pituitary gland, formalin produced no rise in the corticosterone level of the peripheral blood, and operative trauma caused substantially less ascorbic acid depletion than it did in saline-treated controls, although the plasma corticosterone level was normal or below normal.

scholarly journals In vitro and in vivo resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from patients with visceral leishmaniasis.

1997 ◽  
Vol 41 (4) ◽  
pp. 827-830 ◽  
Author(s):  
F Faraut-Gambarelli ◽  
R Piarroux ◽  
M Deniau ◽  
B Giusiano ◽  
P Marty ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Strongly Correlated ◽  
Duration Of Treatment ◽  
In Vitro Sensitivity ◽  
Sensitivity Tests ◽  
Leishmania Parasites ◽  
Immunocompetent Patients

Primary and secondary unresponsiveness to meglumine has long been described in human visceral leishmaniasis. However, no studies have been performed to elucidate if these therapeutic failures were due to strain variability in meglumine sensitivity or were related to host factors. We have studied the in vitro sensitivity of 37 strains of Leishmania infantum isolated from 23 patients (11 human immunodeficiency virus-infected and 12 immunocompetent patients) with visceral leishmaniasis. Sensitivity tests were performed by infecting murine macrophages with Leishmania parasites and culturing them in medium containing different concentrations of meglumine. For each test we calculated a 50% effective dose (ED50) corresponding to the meglumine concentration at which 50% of the Leishmania parasites survived. In vitro results were strongly correlated to immediate clinical outcome. All strains requiring an ED50 of >70 microg/ml were related to therapeutic failures, whereas all strains requiring an ED50 of <40 microg/ml corresponded to an initial efficiency of meglumine. Among those patients who were initially improved, relapses occurred in all immunocompromised patients and in most immunocompetent patients who had a short duration of treatment (15 days). Finally, we found that in vitro sensitivity of strains decreased progressively in relapsing patients treated with meglumine. Consequently, the physician may be encouraged to alternate meglumine with other treatments such as amphotericin B or pentamidine, especially in the case of relapsing patients.

Adrenocortical function in aging exercise-trained rats

1977 ◽  
Vol 43 (5) ◽  
pp. 839-843 ◽  
Author(s):  
J. A. Severson ◽  
R. D. Fell ◽  
J. G. Tuig ◽  
D. R. Griffith
Keyword(s):  
Age Groups ◽  
Plasma Corticosterone ◽  
Treadmill Running ◽  
Adrenocortical Function ◽  
Elevated Plasma ◽  
Corticosterone Concentration ◽  
Relationship Of ◽  
The Relationship

Plasma corticosterone concentrations and in vitro adrenal secretion of corticosterone were determined in exercise-trained rats. Rats, 100, 200, and 300 days of age, were trained for a 10-wk period by treadmill running. Following the training program, rats were subjected to an acute bout of swimming. Acute swimming elevated plasma corticosterone concentrations in all age groups. At 170 days of age, the plasma corticosterone concentration following swimming was higher in exercise-trained rats than in controls. The opposite was true of acutely swum rats at 270 and 370 days of age. Acute swimming elevated the in vitro adrenal gland response to adrenocorticotropic hormone stimulation in control rats at all ages and in trained rats at 170 days of age. The in vivo relationship of epinephrine and the pituitary adrenal system is suggested as a mechanism which could have caused this response. The relationship of secretion rates to plasma corticosterone concentrations indicated that extra-adrenal mechanisms, such as decreased turnover, were also responsible for the elevated plasma corticosterone levels observed in response to acute swimming.

scholarly journals Evaluation of Antibiotic Treatment against “Candidatus Helicobacter suis” in a Mouse Model

2005 ◽  
Vol 49 (11) ◽  
pp. 4530-4535 ◽  
Author(s):  
A. Hellemans ◽  
A. Decostere ◽  
F. Haesebrouck ◽  
R. Ducatelle
Keyword(s):  
Mouse Model ◽  
Antibiotic Susceptibility ◽  
Susceptibility Testing ◽  
Bacterial Dna ◽  
Urease Test ◽  
Slaughter Pigs ◽  
Cessation Of Treatment

ABSTRACT “Helicobacter heilmannii” (proposed name) type 1 colonizes the human stomach. It has been shown to be identical to“ Candidatus Helicobacter suis,” a Helicobacter species colonizing the stomachs of >60% of slaughter pigs. This bacterium has not been isolated in vitro until now. Antibiotic susceptibility testing of “Candidatus Helicobacter suis” has not been carried out so far. For the present study, a mouse model was adopted to evaluate the antibiotic susceptibility of this organism. Mice infected with“ Candidatus Helicobacter suis” were treated with amoxicillin and omeprazole, a therapy which is used to treat H. heilmannii infections in humans. Two different isolates of“ Candidatus Helicobacter suis” were tested. The excretion of bacterial DNA was assessed during treatment, using PCR on fecal samples. At the end of the experiment, 8 days after the cessation of treatment, the presence of infection was evaluated using a urease test and a PCR test on stomach samples. A marked decrease in the excretion of bacterial DNA was observed a few days after the onset of treatment, and the level remained low until the end of the experiment. A difference in susceptibility between the two“ Candidatus Helicobacter suis” isolates was pointed out. The in vivo mouse model infected with“ Candidatus Helicobacter suis” will be useful for further screening of potential therapeutic regimens.

scholarly journals Direct modulation of basal and angiotensin II-stimulated aldosterone secretion by hydrogen ions

2000 ◽  
Vol 166 (1) ◽  
pp. 183-194 ◽  
Author(s):  
RE Kramer ◽  
TV Robinson ◽  
EG Schneider ◽  
TG Smith
Keyword(s):  
Angiotensin Ii ◽  
Free Calcium ◽  
Acid Base Balance ◽  
Aldosterone Secretion ◽  
Plasma Aldosterone Concentration ◽  
Low Concentrations ◽  
Effects Of Ph ◽  
Glomerulosa Cells

Disturbances in acid-base balance in vivo are associated with changes in plasma aldosterone concentration, and in vitro changes in extracellular pH (pH(o)) influence the secretion of aldosterone by adrenocortical tissue or glomerulosa cells. There is considerable disparity, however, as to the direction of the effect. Furthermore, the mechanisms by which pH(o) independently affects aldosterone secretion or interacts with other secretagogues are not defined. Thus, bovine glomerulosa cells maintained in primary monolayer culture were used to examine the direct effects of pH(o) on cytosolic free calcium concentration ([Ca(2+)](i))( )and aldosterone secretion under basal and angiotensin II (AngII)-stimulated conditions. pH(o) was varied from 7.0 to 7.8 (corresponding inversely to changes in extracellular H(+) concentration from 16 nM to 100 nM). Whereas an elevation of pH(o) from 7.4 to 7.8 had no consistent effect, reductions of pH(o) from 7.4 to 7.2 or 7.0 caused proportionate increases in aldosterone secretion that were accompanied by increases in transmembrane Ca(2+) fluxes and [Ca(2+)](i). These effects were abolished by removal of extracellular Ca(2+). A decrease in pH(o) from 7.4 to 7.0 also enhanced AngII-stimulated aldosterone secretion. This effect was more pronounced at low concentrations of AngII and was manifested as an increase in the magnitude of the secretory response with no effect on potency. In contrast to its effect on AngII-stimulated aldosterone secretion, a reduction of pH(o) from 7.4 to 7.0 inhibited the Ca(2+) signal elicited by low concentrations (</=1x10(-10) M) of AngII, but did not affect the increase in [Ca(2+)](i) caused by a maximal concentration (1x10(-8) M) of AngII. These data suggest that pH(o) (i.e. H(+)) has multiple effects on aldosterone secretion. It independently increases aldosterone secretion through a mechanism involving Ca(2+) influx and an increase in [Ca(2+)](i). Also, it modulates the action of AngII by both decreasing the magnitude of the AngII-stimulated Ca(2+) signal and increasing the sensitivity of a more distal site to intracellular Ca(2+). The latter action appears to be a more important determinant in the effects of pH(o) on AngII-stimulated aldosterone secretion.

Tests by Tissue Culture Methods on the Nature of Immunity Transplanted Skin

1948 ◽  
Vol s3-89 (7) ◽  
pp. 239-252
Author(s):  
P. B. MEDAWAR
Keyword(s):  
Tissue Culture ◽  
Cell Division ◽  
Epidermal Cell ◽  
Cell Suspensions ◽  
Acquired Immunity ◽  
Culture Methods ◽  
Division Frequency

The transplantation of skin from one rabbit to another elicits a reaction that conforms in main outline with that of an actively acquired immunity. The experiments described in this paper were designed to test the hypothesis that the regression of such grafts is secured by the action of antibodies demonstrable in vitro. Skin from adult rabbits has therefore been cultivated in the presence of serum and growing mesenchymal tissues derived solely from rabbits heavily and specifically immunized against it. Immune sera and tissues are without effect on the survival, cell-division frequency and migratory activities of explanted skin, and agglutinins for epidermal cell suspensions are not demonstrable in immune sera. With certain stated qualifications, it has therefore been concluded that the occurrence of free antibodies is not a sufficient explanation of the regression of skin homografts in vivo.

Effect of CO2/pH on the aldosterone response to hypoxia in bovine adrenal cells in vitro

1993 ◽  
Vol 265 (4) ◽  
pp. R820-R825
Author(s):  
H. Raff ◽  
B. Jankowski
Keyword(s):  
Respiratory Acidosis ◽  
Inhibitory Effect ◽  
Zona Glomerulosa ◽  
Ang Ii ◽  
Adrenal Cells ◽  
Aldosterone Production ◽  
Per Se ◽  
Air Control

Acidosis increases and hypoxia decreases aldosterone production from the adrenal zona glomulerosa in vivo, in situ, and in vitro. These effects appear to be located at different steps in the steroidogenic process. Because respiratory acidosis and hypoxemia are common sequelae of chronic lung disease, the present experiments evaluated the interaction of hypoxia and CO2 (with uncompensated or compensated extracellular pH) on aldosteronogenesis in vitro. Bovine adrenal zona glomerulosa cells were stimulated with angiotensin II (ANG II) or adenosine 3',5'-cyclic monophosphate under room air control (21% O2-0% CO2), CO2 per se (21% O2-10% CO2), hypoxia per se (10% O2-0% CO2), and the combination of CO2 and hypoxia (10% O2-10% CO2). Furthermore, under CO2, pH was either allowed to decrease from 7.2 to 6.8 (uncompensated) or its decrease was minimized (> 7.05) with NaOH (compensated). CO2 without pH compensation led to a significant increase in ANG II-stimulated aldosterone release; when the decrease in pH was minimized, CO2 inhibited ANG II-stimulated aldosterone release. Hypoxia inhibited aldosterone release; the inhibitory effect of hypoxia predominated when combined with CO2. In the presence of cyanoketone, pregnenolone production from endogenous precursors (early pathway) was unaffected. However, the conversion of corticosterone to aldosterone (late pathway) was inhibited by low O2 but unaffected by CO2. It is concluded that the inhibitory effect of low O2 on the late pathway predominates over the effects of uncompensated or compensated simulated respiratory acidosis on aldosteronogenesis.

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