scholarly journals Oxygen-dependence of ACTH-stimulated aldosterone and corticosterone synthesis in the rat adrenal cortex: developmental aspects

2002 ◽  
Vol 172 (3) ◽  
pp. 595-604 ◽  
Author(s):  
ED Bruder ◽  
AK Nagler ◽  
H Raff
Keyword(s):  
Enzyme Activity ◽  
Age Groups ◽  
Maximal Activity ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Steroid Synthesis ◽  
Camp Generation ◽  
Aldosterone Production ◽  
Health And Disease

The control of ACTH-stimulated steroidogenesis under decreasing levels of O(2) is not fully understood. The purpose of this study was to examine the effects of decreased O(2) in vitro on rat adrenocortical steroid synthesis at different stages of development. Of interest was the evaluation of the effect of low O(2) on steroidogenesis during the stress hyporesponsive period of the neonate. Rats were killed at 7, 14, or 42 days of age, adrenals collected and capsules (zona glomerulosa, ZG) separated from subcapsules (zona fasciculata/reticularis, ZFR). Cells were dispersed and placed into glass vials each gassed with a different level of O(2) (21, 5, 2, 1, or 0% O(2)). The entire steroidogenic pathway was analyzed by measuring ACTH-stimulated cAMP, corticosterone and aldosterone production during a 2 h incubation. In addition, the early (P450 scc) and late (P450c11 beta and P450 aldo) pathway activities were examined in the presence of cyanoketone. The PO(2) for half-maximal activity (P(50)) for aldosterone synthesis in ZG cells from 7- and 42-day-old rats was approximately 28 mmHg and 7 mmHg respectively, indicating that cells from older rats were more resistant to inhibition by low O(2). The P(50) for cAMP production from the ZG was approximately 14 mmHg for both age groups. The P(50) for corticosterone synthesis was approximately 28 mmHg and <7 mmHg in ZFR cells from 7- and 42-day-old cells respectively. The only enzyme activities affected by low O(2) (<35 mmHg) were P450 aldo and P450 scc. Moderate decreases in O(2) (from approximately 150 mmHg) decreased aldosteronogenesis, possibly due to observed decreases in cAMP generation, but not due to decreases in steroidogenic enzyme activity (7-day-old). Severe decreases in O(2) presumably inhibited P450 aldo through a direct effect on enzyme activity (both ages). P450 scc activity (including cholesterol transport) also seems to be decreased by very low O(2) (7-day-old). These findings illustrate a novel developmental alteration in O(2)-regulated steroid production, and may have implications for neonatal health and disease.

VERGLEICHENDE UNTERSUCHUNGEN ZUR BIOGENESE VON STEROIDHORMONEN BEI DURCHSTRÖMUNG ÜBERLEBENDER NEBENNIEREN EINER PATIENTIN MIT CUSHING- UND EINER PATIENTIN MIT CONN-SYNDROM

1963 ◽  
Vol 43 (3) ◽  
pp. 419-429 ◽  
Author(s):  
H. Schriefers ◽  
J. M. Bayer ◽  
M. Pittel
Keyword(s):  
Adrenal Gland ◽  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Secretion Rate ◽  
Zona Fasciculata ◽  
Conn’S Syndrome ◽  
Adrenal Cortical Adenoma ◽  
Aldosterone Production ◽  
The Right

ABSTRACT In vitro perfusion experiments were carried out with adrenal glands surgically removed from a patient with Cushing's syndrome (hyperplasia of the adrenal cortex) and a patient with Conn's syndrome (adrenal cortical adenoma). From the perfusates the following steroids were extracted, estimated and identified: cortisol, corticosterone, 11β-hydroxyandrostenedione, cortisone and aldosterone. The secretion capacities of the right Cushing adrenal and of the adrenal gland bearing the adenoma were compared with each other. In both adrenals cortisol was the main secretion product and the secretion rates of aldosterone were lowest and practically equal. The Cushing adrenal differed from the adrenal gland with the adenoma in its higher secretion rate of all investigated steroids except aldosterone, in its higher cortisol/aldosterone ratio and in its response to the administration of ACTH. To this stimulus the aldosterone production of the Cushing adrenal reacted in the same rate as the cortisol release. The adrenal gland with the adenoma of the patient with Conn's syndrome had only a relatively higher aldosterone secretion rate in respect to its lower cortisol production (lower cortisol/aldosterone ratio). The total preparation consisting of the adrenal with the adenoma responded neither to ACTH nor to hypertensin. The missing response of the adrenal cortex not including the tumor to ACTH is explained by the structural change in the sense of the so called regressive transformation (small zona fasciculata with relative large zona glomerulosa and reticularis) which was found in our case. Dehydroepiandrosterone was demonstrable in none of the perfusate extracts even under the condition where the left adrenal of the Cushing patient was perfused with added 17α-hydroxy-pregnenolone.

Biosynthetic and morphological evidence for inhibition of aldosterone production following administration of ACTH to sheep

1980 ◽  
Vol 94 (4) ◽  
pp. 559-570 ◽  
Author(s):  
John G. McDougal ◽  
Aldona Butkus ◽  
John P. Coghlan ◽  
Derek A. Denton ◽  
Jürg Müller ◽  
...  
Keyword(s):  
Time Course ◽  
Cell Number ◽  
Zona Glomerulosa ◽  
Morphological Evidence ◽  
Zona Fasciculata ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
17 Hydroxyprogesterone ◽  
Zona Glomerulosa Cells

Abstract. The effect of ACTH administration for 1—5 days on the morphology and steroidogenic capability of sheep adrenal tissue has been examined. During this period of treatment there was a gradual decline in the in vitro conversion of 3H-labelled precursors to products of solely zona glomerulosa origin (aldosterone and 18-hydroxycorticosterone) while conversion to products of zona fasciculata origin (17-hydroxyprogesterone, 11-deoxycortisol and cortisol) was stimulated throughout. Conversion to DOC, 18-hydroxydeoxycorticosterone and corticosterone (steroids produced by both the zona glomerulosa and the zona fasciculata) declined after initial stimulation. Within 2—3 days of the commencement of treatment, the zona glomerulosa showed a progressive decrease in cell number associated with disruption of cords and cell separation. Ultrastructurally, it was found that typical zona glomerulosa cells had almost disappeared. The majority of residual cells in this area had a structure intermediate between zona glomerulosa and zona fasciculata cells. The similarity in time-course of the alterations in both the morphological and biosynthetic characteristics suggests that the decline in aldosterone output caused by ACTH administration to sheep results from the loss of adrenal zona glomerulosa cells, predominantly due to selective cellular degeneration.

scholarly journals Quantitative assessment of CYP11B1 and CYP11B2 expression in aldosterone-producing adenomas

2002 ◽  
pp. 795-802 ◽  
Author(s):  
F Fallo ◽  
V Pezzi ◽  
L Barzon ◽  
P Mulatero ◽  
F Veglio ◽  
...  
Keyword(s):  
Real Time ◽  
Secretory Activity ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Pathophysiological Role ◽  
Aldosterone Production

BACKGROUND: The presence and pathophysiological role of CYP11B1 (11beta-hydroxylase) gene in the zona glomerulosa of human adrenal cortex is still controversial. METHODS: In order to specifically quantify CYP11B1, CYP11B2 (aldosterone synthase) and CYP17(17alpha-hydroxylase) mRNA levels, we developed a real-time RT-PCR assay and examined the expression in a series of adrenal tIssues, including six normal adrenals from patients adrenalectomized for renal cancer and twelve aldosterone-producing adenomas (APA) from patients with primary aldosteronism. RESULTS: CYP11B1 mRNA levels were clearly detected in normal adrenals, which comprised both zona glomerulosa and fasciculata/reticularis cells, but were also measured at a lower range (P<0.05) in APA. The levels of CYP11B2 mRNA were lower (P<0.005) in normal adrenals than in APA. CYP17 mRNAlevels were similar in normal adrenals and in APA. In patients with APA, CYP11B2 and CYP11B1 mRNA levels were not correlated either with basal aldosterone or with the change from basal aldosterone in response to posture or to dexamethasone. No correlation between CYP11B1 mRNA or CYP11B2 mRNA and the percentage of zona fasciculata-like cells was observed in APA. CONCLUSIONS: Real-time RT-PCR can be reliably used to quantify CYP11B1 and CYP11B2 mRNA levels in adrenal tIssues. Expression of CYP11B1 in hyperfunctioning zona glomerulosa suggests an additional formation of corticosterone via 11beta-hydroxylase, providing further substrate for aldosterone biosynthesis. CYP11B1 and CYP11B2 mRNA levels in APA are not related to the in vivo secretory activity of glomerulosa cells, where post-transcriptional factors might ultimately regulate aldosterone production.

Abstract 128: Leptin: A Regulator of Aldosterone Synthase Expression & Aldosterone Secretion in Visceral Adipocytes, in Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Eric J Belin de Chantemele ◽  
Anne-Cecile Huby ◽  
P. T Menk ◽  
Weiqin Chen ◽  
Brian Lane ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cross Sections ◽  
Leptin Receptor ◽  
Zona Glomerulosa ◽  
Aldosterone Synthase ◽  
Leptin Receptors ◽  
Fat Depots ◽  
Physiological Relevance ◽  
Aldosterone Production

Obesity is associated with inappropriately high aldosterone levels, which contribute to the development of metabolic and cardiovascular disorders. The origin of these high aldosterone levels is incompletely understood. We recently demonstrated that the adipocyte-derived hormone leptin regulates aldosterone synthase (CYP11B2) expression and stimulates aldosterone release from adrenal zona glomerulosa cells. Recent studies demonstrate that adipocytes express CYP11B2 and secrete aldosterone. However, the mechanisms regulating aldosterone release from adipocytes remain unclear. Likewise, whether visceral (Visc) and subcutaneous (SubQ) adipose tissue contribute to a similar extent to aldosterone production is unknown. We tested the hypothesis that leptin increases adipocyte CYP11B2 expression and aldosterone production and investigated whether Visc and SubQ adipose tissues respond similarly to leptin. Immunostaining of mouse adipose tissue cross-sections and isolated mature adipocytes revealed that Visc and SubQ adipose tissue express leptin receptors. Treatment of mouse freshly isolated mature adipocytes, non-differenciated (stromal fraction) and differentiated adipocytes revealed that leptin dose-dependently increased CYP11B2 expression and aldosterone production in Visc adipose tissue only. Although leptin receptor and CYP11B2 levels were similar in SubQ and Visc adipocytes, SubQ adipocytes were unresponsive to leptin. The physiological relevance of these in vitro data was tested by measuring plasma aldosterone levels in mice deprived of adipose tissue (lipodystrophic mice) treated with leptin. Absence of adipose tissue in lipodystrophic mice blunted leptin-induced increases in aldosterone levels (WT-vehicle: 471±82 vs. WT-Leptin: 1699±396, p<0.05; KO-vehicle: 539±71 vs. KO+leptin: 787±156, NS). The human relevance of these data was determined by reporting that CYP11B2 expression gradually increased with body mass index in human mediastinal and omental fat depots. In summary these data strongly suggest that leptin regulates CYP11B2 levels and aldosterone release in visceral adipose tissue and that leptin-induced, adipocyte-derived aldosterone may contribute to obesity-associated hyperaldosteronism.

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.

Steroid characteristics of mineralocorticoid adrenocortical hypertension

1991 ◽  
Vol 37 (10) ◽  
pp. 1843-1848 ◽  
Author(s):  
E G Biglieri ◽  
C E Kater
Keyword(s):  
Plasma Renin ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Hydroxylase Deficiency ◽  
Aldosterone Production ◽  
Apparent Mineralocorticoid Excess ◽  
Tomography Scan ◽  
Apparent Mineralocorticoid Excess Syndrome ◽  
Hydroxy Steroid ◽  
Steroid Dehydrogenase

Abstract Adrenocortical causes of hypertension are established by examining the mineralocorticoid hormones produced in the zona glomerulosa and zona fasciculata. In the zona glomerulosa, aldosterone excess leads to hypertension, hypokalemia, and suppressed plasma renin activity, with increased concentrations of urinary aldosterone (either as the 18-glucuronide or free aldosterone) as an index of its production. Identifying a tumor by computed tomography scan verifies the diagnosis of a correctable lesion. If no tumor is found, several maneuvers are used to identify primary adrenal hyperplasia, a disorder with autonomous aldosterone production, for which reduction of adrenal mass is curative. The zona fasciculata has two major pathways: the 17-deoxy pathway, where deoxycorticosterone (DOC) and corticosterone are the significant steroids, and the 17-hydroxy pathway, which leads to cortisol production. Tumors of the 17-deoxy pathway, DOC-producing adenomas, have increased concentrations of DOC and its precursor steroids, normal concentrations of cortisol, and suppression of aldosterone production secondary to suppression of the renin system. Two enzymatic defects in the zona fasciculata, 11 beta- and 17 alpha-hydroxylase deficiency, can be first readily identified by the virilization in the former, hypogonadal features in the latter. Steroid patterns are diagnostic. DOC is produced in excess in both deficiencies and is the cause of the hypertension. Deficient or impaired 11 beta-hydroxy steroid dehydrogenase in the apparent mineralocorticoid excess syndrome or after licorice ingestion retards the conversion of cortisol to inactive cortisone in the kidney, leading to mineralocorticoid hypertension; this leads to suppression of the renin system and subsequently of aldosterone.

scholarly journals Aldosterone secretion in patients with septic shock: a prospective study

2013 ◽  
Vol 57 (8) ◽  
pp. 636-641 ◽  
Author(s):  
Rafael Barberena Moraes ◽  
Gilberto Friedman ◽  
Marina Verçoza Viana ◽  
Tiago Tonietto ◽  
Henrique Saltz ◽  
...  
Keyword(s):  
Septic Shock ◽  
Serum Levels ◽  
Zona Glomerulosa ◽  
High Dose ◽  
Zona Fasciculata ◽  
Cortisol Secretion ◽  
Aldosterone Secretion ◽  
Acth Stimulation ◽  
Aldosterone Production ◽  
A Prospective Study

OBJECTIVE: To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS: In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS: Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS: Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

Inhibition of aldosterone release by hypoxia in vitro: interaction with carbon monoxide

1994 ◽  
Vol 76 (2) ◽  
pp. 689-693 ◽  
Author(s):  
H. Raff ◽  
B. Jankowski
Keyword(s):  
Carbon Monoxide ◽  
Angiotensin Ii ◽  
Zona Glomerulosa ◽  
Michaelis Constant ◽  
Aldosterone Synthase ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
In Vitro Interaction ◽  
Zona Glomerulosa Cells

We have demonstrated that the aldosteronogenic pathway of the zona glomerulosa is unusually sensitive to modest changes in PO2 (Michaelis constant for O2 approximately 95 Torr). The current study evaluated the interaction of CO (the classic ligand for P-450 enzymes) and the decreases in O2 on aldosteronogenesis in vitro. Bovine adrenocortical zona glomerulosa cells were incubated for 2 h and stimulated with either adenosine 3′,5′-cyclic monophosphate (cAMP) or angiotensin II. Ten and 20% CO led to significant decreases in cAMP- and angiotensin II-stimulated aldosteronogenesis. The combination of 20% CO and moderate decreases in PO2 (from approximately 140 to approximately 100 Torr) led to an interactive decrease in aldosterone production. The conversion of corticosterone to aldosterone catalyzed by aldosterone synthase, which is the site of O2 sensitivity, was not significantly inhibited by CO. We conclude that the aldosterone pathway is not exceptionally sensitive to CO compared with other steroidogenic pathways. This observation suggests that the unique O2-sensitive properties of the aldosterone pathway located primarily within aldosterone synthase may not reside in its CO binding site (i.e., heme).

IN VITRO RESPONSES OF FOCAL HYPERPLASTIC TISSUE OF THE HUMAN ADRENAL ZONA FASCICULATA TO ACTH

1977 ◽  
Vol 86 (2) ◽  
pp. 363-368 ◽  
Author(s):  
Kenneth V. Honn ◽  
Walter Chavin ◽  
Amnuay Singhakowinta
Keyword(s):  
Adrenocortical Function ◽  
Zona Fasciculata ◽  
Adrenal Tissue ◽  
Basal Cortisol ◽  
Aldosterone Production ◽  
Hyperplastic Tissue ◽  
Normal Human ◽  
Adrenal Zona Fasciculata ◽  
Normal Adrenal Tissue

ABSTRACT The temporal cAMP, cortisol and aldosterone responses to ACTH of focal hyperplasia of the zona fasciculata and of normal human adrenocortical tissue were investigated. ACTH significantly increased cAMP levels (1 min) and cortisol output (2 min) in normal adrenal tissue but not in hyperplastic tissue. However, following ACTH treatment cortisol and aldosterone production were depressed in the abnormal adrenal tissue below the untreated or the ACTH stimulated normal adrenal tissue. In addition, basal cortisol and aldosterone production of the hyperplastic adrenal tissue was elevated above that of the normal adrenal tissue. These findings suggest that the cAMP second messenger concept may be only one of several mechanisms in the modulation of human adrenocortical function.

Effects of corticostatin-I on rat adrenal cells in vitro

1990 ◽  
Vol 125 (2) ◽  
pp. 287-292 ◽  
Author(s):  
T. Tominaga ◽  
J. Fukata ◽  
Y. Naito ◽  
Y. Nakai ◽  
S. Funakoshi ◽  
...  
Keyword(s):  
Specific Binding ◽  
Corticosterone Level ◽  
Inhibitory Effect ◽  
Zona Glomerulosa ◽  
Dependent Manner ◽  
Minimum Effective Concentration ◽  
Adrenal Cells ◽  
Aldosterone Production ◽  
The Media

ABSTRACT We have examined the mechanism by which corticostatin-I (CS-I) acts to attenuate ACTH-induced steroidogenesis in rat adrenal cells. CS-I inhibited ACTH-induced corticosterone production in a dosedependent manner, without any effects on the basal corticosterone level in adrenal cells. When the cells were stimulated by 100 pg ACTH/ml, the minimum effective concentration of CS-I was 100 ng/ml, and 0.3–1.0 μg CS-I/ml produced a 50% reduction of the stimulated corticosterone production. The inhibitory effect of CS-I on ACTH-stimulated corticosterone production became apparent within 15 min of incubation, and the effect was reversed quickly by the removal of CS-I from the media. CS-I had no effect on angiotensin II-stimulated aldosterone production by adrenal zona glomerulosa cells. CS-I also did not affect cyclic AMP- or forskolin-stimulated corticosterone production. In an in-vitro binding study using 125I-labelled CS-I, CS-I showed considerable specific binding to rat adrenal cells, and the binding competed with ACTH in a dose-dependent manner. These experiments suggest that CS-I competes with ACTH on their binding sites and exerts an inhibitory effect on the adrenal cells. Journal of Endocrinology (1990) 125, 287–292

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