DIFFERENT BIOLOGICAL ACTION OF CORTICOSTEROIDS, CORTICOSTERONE AND CORTISOL, AS A BASE OF ZONAL FUNCTION OF ADRENAL CORTEX

1979 ◽  
Vol 91 (2) ◽  
pp. 329-337 ◽  
Author(s):  
A. I. Kahri ◽  
R. Voutilainen ◽  
M. Salmenperä

ABSTRACT The effects of corticosterone and cortisol in concentrations attainable in the adrenal gland were studied on ACTH-induced steroidogenesis in cultured cortical cells of foetal human and rat adrenals. Corticosterone at a concentration of 5.8 × 10−5 mol/l clearly inhibited cortisol production (65.5%; P < 0.005) and simultaneously increased androgen production in tissue culture of foetal human adrenals. Cortisol at a concentration of 2.8 × 10−4 mol/l clearly inhibited 18-OH-DOC (74.0 %, P < 0.001) and aldosterone (83.7 % P < 0.005) production in tissue culture of foetal rat adrenals. In primary culture of foetal human adrenals cortisol did not decrease aldosterone production absolutely, but it significantly decreased the relative amount of aldosterone with respect to corticosterone. Cortisol did not inhibit corticosterone production in either culture. The results demonstrate that cortisol and corticosterone have qualitatively different effects on adrenal steroidogenesis and that these steroids may play a basic role in the functional zonation of the adrenal gland.

Author(s):  
T. M. Murad ◽  
Karen Israel ◽  
Jack C. Geer

Adrenal steroids are normally synthesized from acetyl coenzyme A via cholesterol. Cholesterol is also shown to enter the adrenal gland and to be localized in the lipid droplets of the adrenal cortical cells. Both pregnenolone and progesterone act as intermediates in the conversion of cholesterol into steroid hormones. During pregnancy an increased level of plasma cholesterol is known to be associated with an increase of the adrenal corticoid and progesterone. The present study is designed to demonstrate whether the adrenal cortical cells show any dynamic changes during pregnancy.


1976 ◽  
Vol 70 (2) ◽  
pp. 215-222 ◽  
Author(s):  
M. SALMENPERÄ ◽  
A. I. KAHRI ◽  
A. SAURE

SUMMARY The effects of corticosterone in concentrations found in adrenal venous plasma on ACTH-induced changes in cultured cortical cells derived from foetal rat adrenals were studied. Corticosterone at a concentration of 5·7 × 10−5 mol/l completely inhibited mitochondrial differentiation to fasciculate-like morphology. The same cultures revealed significant inhibition of 11β- and 18-hydroxylation compared with cultures treated with ACTH only. This was shown by the reduced formation of corticosterone and 18-OH-deoxycorticosterone (48%, P < 0·001) and simultaneous enhancement of deoxycorticosterone formation (33%, P < 0·05) from added [4-14C]progesterone. Similar inhibition was observed when dibutyryl cyclic AMP replaced ACTH as an inducer of differentiation. Lower concentrations of corticosterone (1·2 × 10−5 and 2·4 × 10−5 mol/l) inhibited ACTH-stimulated formation of corticosterone and 18-OH-deoxycorticosterone from endogenous precursors. The results demonstrate that corticosterone regulates the stage of differentiation in cultured adrenocortical cells. The possible role of corticosterone in the regulation of growth and steroidogenic capacity of the adrenal cortex is discussed.


1976 ◽  
Vol 71 (3) ◽  
pp. 951-956 ◽  
Author(s):  
A I Kahri ◽  
M Salmenperä ◽  
A Saure

Cortical cells of fetal rat adrenals in tissue culture were treated with 5-bromodeoxyuridine (BrdU) during their proliferative phase and during ACTH stimulation when nuclear DNA synthesis has almost ceased. Pretreatment with 0.5 mug/ml/day of BrdU inhibited the ACTH-induced differentiation of cortical cells as well as the secretion of corticosterone and 18-OH-deoxycorticosterone (18-OHDOC). When nuclear DNA synthesis was suppressed and mitochondrial DNA synthesis was stimulated by ACTH BrdU addition (30 mug/ml/day) permitted normal untrastructural differentiation of cortical cells, except that the development of mitochondrial inner membranes was inhibited. Simultaneously mitochondrial inner membranes was inhibited. Simultaneously mitochondrial 11beta- and 18-hydroxylations were strongly inhibited while cytoplasmic 21-hydroxylation was not affected.


1963 ◽  
Vol 43 (3) ◽  
pp. 419-429 ◽  
Author(s):  
H. Schriefers ◽  
J. M. Bayer ◽  
M. Pittel

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.


2013 ◽  
Vol 305 (9) ◽  
pp. E1049-E1058 ◽  
Author(s):  
Manjunath Ramanjaneya ◽  
Emmanouil Karteris ◽  
Jing Chen ◽  
Marcin Rucinski ◽  
Agnieszka Ziolkowska ◽  
...  

Hormonal regulation of adrenal function occurs primarily through activation of GPCRs. GPCRs are central to many of the body's endocrine and neurotransmitter pathways. Recently, it was shown that activation of GPR103 by its ligand QRFP induced feeding, locomotor activity, and metabolic rate, and QRFP is bioactive in adipose tissue of obese individuals. Given that the adrenal gland is a pivotal organ for energy balance and homeostasis, we hypothesized that GPR103 and QRFP are involved in steroidogenic responses. Using qRT-PCR and immunohistochemistry, we mapped both GPR103 and QRFP in human fetal and adult adrenal gland as well as rat adrenals. Both were primarily localized in the adrenal cortex but not in the medulla. Activation of GPR103 in human adrenocortical H295R cells led to a decrease in forskolin-increased cAMP and an increase of intracellular Ca2+ levels. In addition, treatment of H295R cells with QRFP induced aldosterone and cortisol secretion as measured by ELISA. These increases were accompanied by increased expression and activity of StAR, CYB11B1, and CYP11B2 as assessed by qRT-PCR and luciferase reporter assay, respectively. Using specific inhibitors, we also demonstrated that aldosterone induction involves MAPK, PKC, and/or T-type Ca2+ channel-dependent pathways. These novel data demonstrate that QRFP induces adrenal steroidogenesis in vitro by regulating key steroidogenic enzymes involving MAPK/PKC and Ca2+ signaling pathways.


1976 ◽  
Vol 83 (4) ◽  
pp. 781-793 ◽  
Author(s):  
M. Salmenperä ◽  
A. I. Kahri

ABSTRACT A method for simultaneous analysis of the main corticosteroids secreted by the rat adrenal is described. Purification is performed using previously established steps involving dichloromethane extraction, ethanol-cyclohexane partition and Sephadex-LH-20 column chromatography. Deoxycorticosterone and aldosterone are then quantitated with radioimmunoassay and corticosterone and 18-hydroxy-deoxycorticosterone with gas liquid chromatography as their 0-methyloxime-trimethylsilyl ethers. The coefficient of variation of the method for these steroids in concentrations found in the tissue culture of foetal rat adrenals varies between 3.9–10.9% The secretion of these steroids in the tissue culture of foetal rat adrenals is studied. The steroid secretory pattern is correlated with a differentiation stage of the cultures as detected by electron microscopy. The initial secretory activity declines considerably after 15 days of cultivation to a low level. This is the case also with respect to aldosterone although the cortical cell population changed from the mixed population of the differentiated (zona fasciculata-like) and undifferentiated (zona glomerulosa-like) cells to homogenous undifferentiated growth. Addition of ACTH increased deoxycorticosterone secretion rapidly. Corticosterone, 18-hydroxy-deoxycorticosterone and aldosterone secretion was observed only after the differentiation of the cells (especially changes in their mitochondrial compartment) was evident morphologically.


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