OUTPUT OF OESTROGENS, TESTOSTERONE AND THEIR PRECURSORS BY ISOLATED HUMAN ADRENAL CELLS AS COMPARED WITH THAT OF GLUCOCORTICOSTEROIDS

1976 ◽  
Vol 71 (2) ◽  
pp. 219-229 ◽  
Author(s):  
V. KEYMOLEN ◽  
P. DOR ◽  
A. BORKOWSKI
Keyword(s):  
Adrenal Cortex ◽  
Acth Stimulation ◽  
Adrenal Cells ◽  
Selective Stimulation ◽  
Order Of Magnitude ◽  
Adrenal Secretion ◽  
Free Steroid ◽  
Stimulation Of ◽  
Sigmoid Shape

SUMMARY The output of oestrogens, testosterone and their precursors was compared with that of glucocorticosteroids under standardized conditions, in a suspension of isolated human adrenal cells. Cortisol, corticosterone, androstenedione, dehydroepiandrosterone and its sulphate all increased in the same proportions after ACTH stimulation. The response to the logarithm of ACTH concentrations had a sigmoid shape but was fairly linear between 5 and 100 to 1000 μu./ml. The output of dehydroepiandrosterone plus that of its sulphate was of the same order of magnitude as the production of cortisol; the output of free dehydroepiandrosterone averaged half that of the sulphate indicating that the adrenal cortex is capable, under certain conditions, of producing large amounts of the free steroid. The output of androstenedione was very low, on average 35 times lower than that of cortisol, suggesting by extrapolation that the adrenal secretion may not be the main source of androstenedione in vivo or that ACTH is not the unique stimulus to adrenal androstenedione secretion. The output of testosterone was small to negligible and that of oestrogens was practically absent. In three additional experiments the influence of prolactin, prostaglandins, FSH and HCG was explored: no selective stimulation of androgen or oestrogen output was observed except in one experiment in which HCG stimulated adrenal testosterone production.

A Novel α-Conotoxin Identified by Gene Sequencing Is Active in Suppressing the Vascular Response to Selective Stimulation of Sensory Nerves in Vivo†

Biochemistry ◽  
2003 ◽  
Vol 42 (22) ◽  
pp. 6904-6911 ◽  
Author(s):  
D. W. Sandall ◽  
N. Satkunanathan ◽  
D. A. Keays ◽  
M. A. Polidano ◽  
X. Liping ◽  
...  
Keyword(s):  
Gene Sequencing ◽  
Sensory Nerves ◽  
Vascular Response ◽  
Selective Stimulation ◽  
Stimulation Of

PROPERTIES OF RAT ADRENAL ZONA RETICULARIS CELLS: PRODUCTION AND STIMULATION OF CERTAIN STEROIDS

1979 ◽  
Vol 83 (3) ◽  
pp. 435-447 ◽  
Author(s):  
J. B. G. BELL ◽  
R. P. GOULD ◽  
P. J. HYATT ◽  
J. F. TAIT ◽  
S. A. S. TAIT
Keyword(s):  
Adrenal Cortex ◽  
Significant Role ◽  
Zona Fasciculata ◽  
Cell Type ◽  
Acth Stimulation ◽  
Specific Stimulus ◽  
Zona Reticularis ◽  
Cell Pool ◽  
Stimulation Of

The outputs of corticosterone, deoxycorticosterone and androstenedione from dispersed, purified rat adrenal zona reticularis and zona fasciculata cells have been measured by radioimmunoassay. Preferential production of deoxycorticosterone by zona reticularis cells was demonstrated by their higher basal deoxycorticosterone: corticosterone ratio when compared with zona fasciculata cells. Adrenocorticotrophin (ACTH) stimulated corticosterone output by all cell pools prepared by unit gravity (1 g) sedimentation, zona fasciculata cells being stimulated 130-fold compared with 20-fold for the zona reticularis cells in relation to their basal corticosterone output. In every cell pool, ACTH stimulated the output of corticosterone more than it stimulated the output of deoxycorticosterone. In parallel cell preparations, it was shown that ACTH increased the conversion of tracer amounts of radioactive deoxycorticosterone to corticosterone and decreased the conversion of radioactive corticosterone to 11-dehydrocorticosterone. Adrenocorticotrophin did not increase the conversion of radioactive deoxycorticosterone to total 11-oxygenated steroids (corticosterone+ 11-dehydrocorticosterone). It is unlikely therefore that ACTH stimulates 11 β-hydroxylation. Data indicate that the ratio of deoxycorticosterone to total 11-oxygenated steroids (corticosterone +11-dehydrocorticosterone) is characteristic for each cell type, and that this ratio will be relatively independent of ACTH stimulation or the amount of pregnenolone substrate available. Basal androstenedione outputs were similar for both types of cell, and ACTH stimulation was very small, being slightly greater for zona fasciculata than for zona reticularis cells. The contribution of the zona reticularis cells to the basal output of any steroid by the cells of the inner two zones of the adrenal cortex of the rat was relatively small (20% for deoxycorticosterone and 10% for corticosterone) and was even less after stimulation by ACTH. Unless a specific stimulus can be found, therefore, a significant role for the zona reticularis cannot yet be established.

scholarly journals Measurement of the dynamics of stimulation and inhibition of steroidogenesis in isolated rat adrenal cells by using column perfusion

1974 ◽  
Vol 142 (2) ◽  
pp. 287-294 ◽  
Author(s):  
P. J. Lowry ◽  
Colin McMartin
Keyword(s):  
Cyclic Amp ◽  
Time Course ◽  
Acth Stimulation ◽  
Duration Of Action ◽  
Adrenal Cells ◽  
Small Column ◽  
Long Duration ◽  
Full Effect ◽  
Rapid Fall

Isolated adrenal cells were perfused in a small column by using Bio-Gel polyacrylamide beads as an inert supporting matrix, and the time-course of the response to various stimuli was observed by measuring fluorogenic 11-hydroxycorticosteroids in the effluent. A small but significant response was observed 1 min after stimulation with physiological concentrations of ACTH (adrenocorticotrophin), but the response did not start to build up rapidly for 3–4min and eventually reached a plateau after 9–10min. A similar pattern of events was observed for the decay of the steroid output on removal of ACTH. ACTH analogues, including one with a long duration of action in vivo, were found to produce responses with similar kinetics. However, cyclic AMP caused a more rapid increase in steroidogenesis and its effects were more short-lived after withdrawal. If, as present evidence suggests, cyclic AMP is produced rapidly after ACTH stimulation the delayed build-up of the steroidogenic response to ACTH would indicate that cyclic AMP may not be the intracellular mediator. When inhibitors were applied during ACTH stimulation, aminoglutethimide, which blocks mitochondrial conversion of cholesterol into pregnenolone (3β-hydroxypregn-5-en-20-one), caused a rapid fall in steroid output (1 min), whereas cycloheximide took longer to achieve its full effect. Nevertheless, the response had fallen by 50% in 2 min, indicating a much shorter half-life than that previously reported for the labile protein implicated in steroidogenesis. In addition the rapid response to cyclic AMP makes it unlikely that steroid production is induced as a result of initiation of protein synthesis. This suggests that the labile protein plays an obligatory but permissive role in the development of the response. Column perfusion has proved to be a simple technique which can readily yield accurate data on responses of cells to stimulants and inhibitors.

Selective autonomic stimulation of canine trachealis with dimethylphenylpiperazinium

1981 ◽  
Vol 51 (2) ◽  
pp. 428-437 ◽  
Author(s):  
A. R. Leff ◽  
N. M. Munoz
Keyword(s):  
Adrenal Gland ◽  
Contractile Response ◽  
Sympathetic Innervation ◽  
Adrenergic Stimulation ◽  
Parasympathetic Ganglia ◽  
Regional Administration ◽  
Adrenal Secretion ◽  
Stimulation Of

The response of canine tracheal muscle to autonomic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) was studied isometrically in 39 dogs in vivo. Intra-arterial (ia) DMPP (2.5 X 10(-4) to 2.5 X 10(-2) mg/kg) caused selective dose related contraction [maximum 30.1 +/- 6.5 gram-force (gf)/cm] due to regional stimulation of parasympathetic ganglia. This contraction was blocked by regional administration of atropine 10(-3) mg/kg ia and hexamethonium 5 X 10(-2) mg/kg ia. Nonselective intravenous (iv) administration of DMPP 2.5 X 10(-2) mg/kg caused parasympathetic tracheal contraction [+13.4 +/- 1.64 gf/cm] followed by later sympathetic relaxation [-11.8 +/- 2.3 gf/cm]; 0.5 mg/kg iv atropine abolished contraction but did not affect relaxation. The role of the adrenal gland vs. direct sympathetic innervation in producing tracheal relaxation after sympathetic stimulation was also studied. Tracheal relaxation to 2.5 X 10(-2) mg/kg iv DMPP was -18.2 +/- 4.0 gf/cm before adrenalectomy (ADX) and -4.3 +/- 0.9 gf/cm afterward (P less than 0.001). In contrast, tracheal contraction resulting from alpha-adrenergic stimulation after 2.5 X 10(-2) mg/kg iv DMPP in beta-blocked (BB) dogs was not significantly altered by ADX. At 2.5 X 10(-1) mg/kg iv DMPP, the alpha-adrenergic contractile response was still 70% of the response prior to ADX. We conclude that sympathetic tracheal relaxation in dogs is predominantly mediated by circulating catecholamine from the adrenal gland, but that alpha-adrenergic contraction after BB results predominantly from direct sympathetic innervation and is not greatly augmented by adrenal secretion. We also report a new method for selective stimulation of airway cholinergic nerves in vivo without systemic effects.

scholarly journals beta-Naphthoflavone abolishes interrenal sensitivity to ACTH stimulation in rainbow trout

1998 ◽  
Vol 157 (1) ◽  
pp. 63-70 ◽  
Author(s):  
JM Wilson ◽  
MM Vijayan ◽  
CJ Kennedy ◽  
GK Iwama ◽  
TW Moon
Keyword(s):  
Cytochrome P450 ◽  
Rainbow Trout ◽  
Acth Stimulation ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Treated Fish ◽  
First Time ◽  
Hepatic Cytochrome ◽  
Stimulation Of

We report for the first time that beta-naphthoflavone (BNF) abolishes ACTH stimulation of cortisol production in rainbow trout (Oncorhynchus mykiss). There was significantly higher hepatic cytochrome P450 content and ethoxyresorufin O-de-ethylase and uridine-5'-diphosphoglucuronic acid transferase activities in BNF-treated fish than in sham-treated controls. BNF did not significantly affect either plasma turnover or tissue distribution of [3H]cortisol-derived radioactivity. Hepatic membrane fluidity and hepatocyte capacity for cortisol uptake were not altered by BNF as compared with the sham-treated fish. These results taken together suggest that BNF does not affect cortisol-clearance mechanisms in trout. A 3 min handling disturbance period elicited a plasma cortisol response in the sham-treated fish; however, the response in the BNF-treated fish was muted and significantly lower than in the sham fish. This in vivo response corroborates the lack of interrenal sensitivity to ACTH in vitro in the BNF-treated fish, suggesting that BNF affects the ACTH pathway in trout. Our results suggest the possibility that cytochrome P450-inducing compounds may affect cortisol dynamics by decreasing interrenal responsiveness to ACTH stimulation in fish, thereby impairing the physiological responses that are necessary for the animal to cope with the stressor.

CORTICOID PRODUCTION IN VITRO AS A TEST OF ADRENOCORTICAL FUNCTION IN RATS

1960 ◽  
Vol XXXIII (I) ◽  
pp. 59-66 ◽  
Author(s):  
J. van der Vies
Keyword(s):  
Adrenal Cortex ◽  
Adrenal Function ◽  
The Other ◽  
Adrenocortical Function ◽  
Experimental Conditions ◽  
Adrenal System ◽  
Other Hand ◽  
Stimulation Of

ABSTRACT Adrenal function in rats under various experimental conditions was studied by incubating the adrenals in vitro and determining the corticosteroid output during one hour. This in vitro corticoid production was reduced after hypophysectomy, hypothalamus-lesioning and treatment with hydrocortisone or with Nembutal and morphine. On the other hand, an increased production was observed following stimulation of the pituitary-adrenal system by exogenous histamine or corticotrophin. From these experiments it is concluded that the corticoid production in vitro reflects the activity of the adrenal cortex in vivo and hence can be used for the study of the latter function.

scholarly journals Adrenocorticotropin Acutely Regulates Pregnenolone Sulfate Production by the Human Adrenal In Vivo and In Vitro

2017 ◽  
Vol 103 (1) ◽  
pp. 320-327 ◽  
Author(s):  
Juilee Rege ◽  
Aya T Nanba ◽  
Richard J Auchus ◽  
Jianwei Ren ◽  
Hwei-Ming Peng ◽  
...  
Keyword(s):  
Dehydroepiandrosterone Sulfate ◽  
Zona Fasciculata ◽  
Serum Samples ◽  
Acth Stimulation ◽  
Pregnenolone Sulfate ◽  
Adrenal Cells ◽  
Sulfate Production ◽  
Before And After

Abstract Background Dehydroepiandrosterone sulfate (DHEAS) is the most abundant steroid in human circulation, and adrenocorticotropic hormone (ACTH) is considered the major regulator of its synthesis. Pregnenolone sulfate (PregS) and 5-androstenediol-3-sulfate (AdiolS) have recently emerged as biomarkers of adrenal disorders. Objective To define the relative human adrenal production of Δ5-steroid sulfates under basal and cosyntropin-stimulated conditions. Methods Liquid chromatography-tandem mass spectrometry was used to quantify three unconjugated and four sulfated Δ5-steroids in (1) paired adrenal vein (AV) and mixed venous serum samples (21 patients) and (2) cultured human adrenal cells both before and after cosyntropin stimulation, (3) microdissected zona fasciculata (ZF) and zona reticularis (ZR) from five human adrenal glands, and (4) a reconstituted in vitro human 17α-hydroxylase/17,20-lyase/(P450 17A1) system. Results Of the steroid sulfates, PregS had the greatest increase after cosyntropin stimulation in the AV (32-fold), whereas DHEAS responded modestly (1.8-fold). PregS attained concentrations comparable to those of DHEAS in the AV after cosyntropin stimulation (AV DHEAS/PregS, 24 and 1.3 before and after cosyntropin, respectively). In cultured adrenal cells, PregS demonstrated the sharpest response to cosyntropin, whereas DHEAS responded only modestly (21-fold vs 1.8-fold higher compared with unstimulated cells at 3 hours, respectively). Steroid analyses in isolated ZF and ZR showed similar amounts of PregS and 17α-hydroxypregnenolone in both zones, whereas DHEAS and AdiolS were higher in ZR (P < 0.05). Conclusion Our studies demonstrated that unlike DHEAS, PregS displayed a prominent acute response to cosyntropin. PregS could be used to interrogate the acute adrenal response to ACTH stimulation and as a biomarker in various adrenal disorders.

Backdiffusion of H+ in isolated frog gastric mucosa

1984 ◽  
Vol 246 (2) ◽  
pp. G114-G119
Author(s):  
R. P. Durbin
Keyword(s):  
Gastric Mucosa ◽  
Ion Pair ◽  
Substantial Part ◽  
Direct Titration ◽  
Maximal Stimulation ◽  
Gastric Potential Difference ◽  
Normal Resistance ◽  
Order Of Magnitude ◽  
Stimulation Of

Backdiffusion of H+ was studied in isolated bullfrog gastric mucosa using direct titration to evaluate changes in luminal H+ level. In resting mucosae, the resulting permeability coefficient for H+ (uncorrected for electrical effects) was 0.4 X 10(-5) cm X S-1, which is of the same order of magnitude as that estimated from data in the literature for dog and rabbit gastric mucosa in vivo. With maximal stimulation of acid secretion, backdiffusion of H+ was considerably increased. In both resting and stimulated mucosae, an increase in Cl- flux from lumen to serosa was observed to accompany H+ backdiffusion. In experiments in which electrical activity of resting mucosae was monitored, instilled H+ lowered gastric potential difference but had little effect on the normal resistance. Sudden drops in resistance and potential were observed, independent of luminal acid; after such events instilled H+ had no effect on mucosal resistance. It appears that a substantial part of H+ backdiffusion occurs as the ion pair HCl.

The mechanism of the effect of K + on the steroidogenesis of rat zona glomerulosa cells of the adrenal cortex: role of cyclic AMP

1986 ◽  
Vol 227 (1246) ◽  
pp. 21-42 ◽  
Keyword(s):  
Cyclic Amp ◽  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Free Concentration ◽  
Mean Values ◽  
Glomerulosa Cells ◽  
Zona Glomerulosa Cells ◽  
Stimulation Of

The effects of various concentrations of extracellular K + (3.6 - 13 mM) on the steroid (corticosterone and aldosterone) and cyclic AMP outputs of capsular cells (95% zona glomerulosa) of the rat adrenal cortex were studied at different concentrations of extracellular Ca 2+ . Small amounts of EGTA (50 μM) were added to reduce the free Ca 2+ concentrations effectively to zero at the lowest possible total Ca 2+ concentration. At a total extracellular concentration of 2.5 mM Ca 2+ , in 27 experiments the mean values of the steroid and cAMP outputs showed a maximum at 8.4 mM K + . The increase in steroid and cAMP outputs at 5.9, 8.4 and 13 mM K + compared with that at 3.6 mM were highly significant ( p < 0.01). The overall correlation of either corticosterone or aldosterone with cAMP outputs was also highly significant and was even better from 3.6 to 8.4 mM K + . Lowering the effective free concentration of Ca 2+ to zero decreased the steroid and cAMP outputs significantly at all K + concentrations, and no output was then significantly higher than at 3.6 mM. With the pooled data on outputs at all total Ca 2+ (2.5, 0.5, 0.25, 0.10, 0.05 and 0.0 mM) and K + (3.6, 5.9, 8.4 and 13 mM) concentrations, the correlation of either steroid with cAMP outputs was highly significant (but again optimally from 3.6 to 8.4 mM K + ). Nifedipine (10 -6 to 10 -4 M) was added to the incubations with the aim of specifically inhibiting Ca 2+ influx at total extracellular Ca 2+ concentra­tions of 2.5, 1.25 and 0.25 mM and with the usual K + concentrations. The cAMP outputs were reduced at all K + concentrations above 3.6 mM K + . The effect was highly significant at 10 -4 M nifedipine and a total Ca 2+ of 1.25 mM, which with the incubation conditions used, corresponds to the free Ca 2+ concentrations in vivo . These results indicate that cAMP plays a significant role in the stimulation of steroid output by K + particularly between 3.6 and 8.4 mM K + . In this range of K + concentrations the stimulation of cAMP seems to be controlled by increases in Ca 2+ influx. The correlation of steroid and cAMP output at the higher K + concentra­tions (between 8.4 and 13 mM K) and at the various total Ca 2+ concentra­tions is less significant. Also, with all concentrations of added nifedipine there is an ‘anomalous’ increase in steroid output at 13 mM K + and at total Ca 2+ concentrations of 2.5 and 1.25 mM. However, at the same K + concentrations and at 0.25 mM Ca 2+ , nifedipine decreases steroid outputs. Our previous data, obtained after addition of maximally effective amounts of cAMP, indicated that there were also non-cAMP mechanisms involved in the stimulation of steroidogenesis by K + in z. g. cells. The present data confirm this conclusion, particularly at K + concentrations above 8.4 mM. They also indicate that at these higher K + concentrations, by non-cAMP mechanisms increasing intracellular Ca 2+ concentrations probably inhibit steroidogenesis. We conclude, however, that in the physiological range of K + concentra­tions, the role of cAMP in zona glomerulosa cells is at least comparable in importance to that of non-cAMP mechanisms.

scholarly journals Selective stimulation of mast cells with a TLR2 agonist inhibits tumor growth in vivo

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Sharon Ann Oldford ◽  
Carlos A. Leiva ◽  
Brent Johnston ◽  
Jean S. Marshall
Keyword(s):  
Mast Cells ◽  
Tumor Growth ◽  
Tlr2 Agonist ◽  
Selective Stimulation ◽  
Stimulation Of
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