[Effects of estradiol on synthesis of corticosteroids, protein kinase A and C activity in the adrenal cortex of intact and orchiectomized rats].

Estradiol treatment produced significant increase of total 11-hydroxycorticosteroids level in the blood of intact and castrated rats. Activity of protein kinase A increased in the cytosol and membrane fraction of adrenocorticocytes of intact and orchiectomized rats after estradiol influence. Activity of protein kinase C significantly raised in the cytosol and membrane fraction of adrenocortical cells in all investigated groups. Our results suggest that cAMP-dependent protein kinase A and protein kinase C mediate estradiol effects in adrenal cortex.

Especificidad de acción de la aldosterona e hipertensión arterial / Specificity of the action of aldosterone and arterial hypertension

La enzima 11 beta-hidroxiesteroide deshidrogenasa tipo 2 (11 HSD2) confiere la especificidad de la acción de la aldosterona respecto a otros corticoides circulantes (cortisol) en los tejidos que deben responder de forma específica a los mineralocorticoides. Esta especificidad debe darse sobre todo en ciertos epitelios transportadores de sodio como el túbulo distal del riñón y en el colon. Esta enzima, poco conocida hasta hace unos años, se está revelando como de gran importancia, ya que interviene en la regulación de la presión arterial. En primer lugar, mutaciones del gen que codifica la enzima causan una forma rara de hipertensión sal sensible de herencia mendeliana autosómica recesiva conocida como exceso aparente de mineralocorticoides (AME). En segundo lugar, se ha determinado que en la población normal, polimorfismos genéticos en 11 HSD2 se asocian con una reducción de la actividad de la enzima in vivo. Esta reducción de la actividad enzimática así como los polimorfismos genéticos que la determinan se han relacionado con un incremento de la respuesta presora a la ingestión elevada de sal, fenómeno conocido como sensibilidad a la sal, tanto en sujetos sanos como en pacientes con hipertensión arterial esencial. Por tanto, es un gen candidato que intervendría en la patogenia de la hipertensión arterial (HTA) "esencial", sobre todo sensible a la sal y que debe aún ser estudiado en mayor profundidad (AU)

[Effect of Ca2+- and K+-channel blockers on ACTH-stimulated steroidogenesis of isolated adrenal glands of adult and old rats]. / Vliianie blokatorov Ca2+- i K+-kanalov na AKTG-stimulirovannyi steroidogenez izolirovannykh nadpochechnikov vzroslykh i starykh krys.

Ca2+ channel blocker verapamil (0.2 mM) and K+ channel blocker 2-aminopyridine (1.0 mM; 5.0 mM and 10.0 mM) have been studied for their effect on ACTH-stimulated steroidogenesis in isolated adrenal glands (IAG) of the adult (6-7 months) and old (26-28 months) male rats. The administration of verapamil produced a similar, about 2-fold decrease in ACTH-stimulated secretion of 11-OCS in the IAG of both animal groups. 2-aminopyridine, administered in several concentrations, produced no effect whatsoever on ACTH-stimulated secretion of 11-OCS in the IAG of the old rats. However, when administered in concentrations of 5.0 mM and 10.0 mM this agent decreased significantly the ACTH-stimulated steroidogenesis in the IAG of the adult animals. It has been suggested that plasma membrane permeability of z. fasciculata adrenocorticocytes to K+ ions decreases with age.

Regulation of 18-hydroxycorticosterone formation in bovine adrenocortical mitochondria.

The conversion of deoxycorticosterone to 18-hydroxycorticosterone was examined by using sonicated mitochondrial suspension of bovine adrenocortex. The KM's of deoxycorticosterone for the 11 beta- and 18-hydroxylations were in the same range (1 microM), while the turnover number for the 11 beta-hydroxylation (50 nmol/min/nmol cytochrome P-450) was 6 times as great as that for the 18-hydroxylation (7.3). The KM and turnover number for the 18-hydroxylation of corticosterone were 6 microM and 0.4, respectively. Those for the 11 beta-hydroxylation of 18-hydroxy-11-deoxycorticosterone were 120 microM and 5. When products were analysed in the incubation of deoxycorticosterone with the mitochondrial suspension containing a larger amount of cytochrome P-450, the formation of 18-hydroxycorticosterone was observed in addition to the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone. The kinetic interrelation between the two pathways was further examined together with consideration of the cytochrome P-450-linked hydroxylation system. The result suggests that the pathway via 18-hydroxy-11-deoxycorticosterone substantially participates in the formation of 18-hydroxycorticosterone from deoxycorticosterone. The perturbation of this network by an artificial means, such as the addition of Triton X-100, revealed that the detergent (0.02%) facilitated the production of 18-hydroxycorticosterone from deoxycorticosterone, regardless of its inhibitory effect on the production of corticosterone and 18-hydroxy-11-deoxycorticosterone from deoxycorticosterone. These studies provide an important insight into the regulation mechanism of 18-hydroxycorticosterone formation from the precursors on the mitochondrial level.

Direct effect of histamine on the production of adrenocortical hormone by guinea-pig adrenal cells.

In trypsin-dispersed adrenal cells of the guinea-pig, the production of 11-hydroxycorticosteroids in vitro was found to be significantly stimulated by 10(-7) -10(-4)M histamine and the maximum steroidogenic response (1.7-fold increase in 11-hydroxycorticosteroid production) was observed at 10(-6)M. The stimulatory action of histamine on steroidogenesis was blocked by cycloheximide treatment.

[The effect of prostaglandins on steroidogenesis in isolated human and bovine adrenal cells: a study of the effect of the ACTH action mechanism (author's transl)].

It has been reported that prostaglandins (PGs) stimulate steroidogenesis in the adrenal glands of various mammarian species. However, the exact role of PGs in steroidogenesis remains unclear. Therefore, attempts were made to clarify the action mechanism of PGs on steroidogenesis. The production of 11-OHCS in adrenal cells was stimulated by ACTH, PGE2 and PGF2 alpha. PGE2 increased the c-AMP level, but PGF2 alpha had no effect on it. No effect was observed by indomethacin or theophylline on the production of 11-OHCS by ACTH. Cycloheximide inhibited the elevation in 11-OHCS by PGE2 and PGF2 alpha. Different results were observed: PGs-combined effects of varying concentrations of ACTH were additive, PGs-combine effects of varying concentrations of dbc-AMP were synergic, and simultaneous incubation of maximal concentrations of ACTH and PGs failed to elicit a supramaximal response. These results suggest that PGs act like ACTH on steroidogenesis in human and bovine adrenals and are in keeping with the hypothesis that the action of ACTH and PGs in steroidogenesis is Ca++ influx in the adrenal cells.

[Role of the adrenal glands in the cytostatic action mechanism of antitumor antibiotics]. / O roli nadpochechnikov zhelez v mekhanizme tsitostaticheskogo deistviia protivoopukholevykh antibiotikov.

The state of the steroidogenic function of the adrenal glands, lipid spectrum of the adrenal gland tissue and metabolism rate of 11-oxycorticosteroids (11-OCS) in the liver tissue and their levels in the blood plasma were studied on rats after a single administration of karminomycin in a dose of LD50 (1.55 mg/kg). The hormones of the adrenal cortex were shown to play a definite role in the mechanism of the karminomycin damaging effect. Dependence of the changes on the time of the drug effect was noted. The shifts were of a reversible character. No direct toxic damages in the tissue of the adrenal glands were observed. Only an increase in the 11-OCS blood levels and a decrease in the steroid metabolism in the liver tissue were shown. The latter must be due to the direct cytotoxic effect of karminomycin on the tissue of this organ.

[Comparative study of several structuro-functional parameters of the liver and adrenal cortex in mice of different genetic strains under physiologically normal conditions]. / Sravnitel'noe issledovanie nekotorykh strukturno-funktsional'nykh pokazatelei pecheni i kory nadpochechnikov myshei raznykh geneticheskikh linii v usloviiakh ifziologicheskoi normy.

In adult male mice CBA and C57BL there were revealed differences in the morphometric characteristics of the subcellular organization of hepatocytes, as well as in the indices of functional capacity of the adrenal cortex and the rate of metabolism of steroid hormones in the liver. In animals of the strains under study the levels of steroid hormones production by the adrenal cortex and the rate of gross metabolism of steroid hormones in the liver were characterized by inverse relationship. Structural-functional indices of the adrenal cortex and the liver are supposed to cause different liver responses in these strains of mice to the influence of the alterating factors.

[The effect of calcium on steroidogenesis in isolated human adrenal cells (author's transl)].

The present experiment was planned to verify the effect of calcium on adenyl cyclase in isolated human adrenal cells. Normal adrenal glands were obtained surgically from patients with primary aldosteronism and advanced breast cancer. Isolated adrenal cells were prepared by the modified Haning's method. They were incubated at 37C under a gas mixture of 95 percent O2: 5 percent CO2 in calcium-free Krebs-Ringer bicarbonate buffer solution containing 0.2 percent glucose and 0.5 percent fatty acid-free bovine serum albumin, to which various doses of CaCl2 or ACTH were added. Thirty minutes later, cyclic-AMP was measured by cyclic-AMP assay kit (The Radio-chemical Center, Amersham). 11-OHCS was estimated fluorometrically by the modified Silber's method after incubation for 2 hours. In the calcium-free incubation medium, productions of 11-OHCS and cyclic-AMP were negligible. In the concentration of 2.54 mM/L of calcium, 11-OHCS production increased with significant difference statistically, while the increase of cyclic-AMP production was not significant. In the concentration of 12.70 mM/L of calcium, however, cyclic-AMP production increased remarkably. When ACTH was added to the incubation medium containing 2.54 mM/L of calcium, productions of 11-OHCS and cyclic-AMP also increased remarkably. These results indicate that adenyl cyclase of human adrenocortical cells is directly stimulated by calcium and suggest that calcium acts as the second messenger of ACTH.

[Study of the relationship between the glucocorticoid function of the adrenal cortex and blood lipoproteins]. / Izuchenie vzaimootnoshenii mezhdu gliukokortikoidnoi funktsiei kory nadpochechnikov i lipoproteidami syvorotki krovi.

Single administration of hydrocortisone to rats led to elevation in the blood serum of lipoproteins of very low density; and repeated administration - of lipoproteins of very low density, low density and of high density. Lipoproteins with d less than 1.063 g/ml produced an inhibitory action on the production of steroid hormones by the adrenal glands of rats in vitro.

[Changes in the functional state and structure of the adrenals in CC14 poisoning]. / Izmeneniia funktsional'nogo sostoianiia i struktury nadpochechnikov pri intoksikatsii CC14

Introduction of CCI4 in doses of 0.1 and 0.2 ml/100 g to albino rats reduced the steroid production generated by adrenal sections. In 24 and 48 hours after poisoning with a small dose of CCI4 (0.1 ml/100 g) there could be seen an increased concentration of 11-oxycorticosteroids in the plasma. Morphological signs of a damage suffered by the gland were observed only in poisoning with a large dose of CCI4 (0.2 ml/100 g).