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Modulation of IL-18 production in the adrenal cortex following acute ACTH or chronic corticosterone treatment.

Interleukin (IL)-18 is a proinflammatory cytokine and a stimulator of cell-mediated immune responses. We have previously reported that acute stress stimulates the production of IL-18 mRNA in the glucocorticoid (GC)-producing cells of the adrenal cortex. In order to investigate the mechanisms governing the expression of IL-18 in the adrenal cortex, the effects of acute ACTH or chronic corticosterone treatment on the levels of IL-18 mRNA and protein were examined by in situ hybridization and Northern and Western blot assays. Adult male Sprague-Dawley rats received a subcutaneous injection of ACTH or subcutaneous implantation of slow-release corticosterone pellets followed by an injection of saline or ACTH. After 4 h, ACTH induced a 4-fold increase in IL-18 mRNA levels and elevated the content of pro-IL-18 peptide. Six days of chronic corticosterone treatment did not alter the basal levels of IL-18 mRNA and reduced those of pro-IL-18. Finally, ACTH treatment of animals under the corticosterone regimen induced a 2-fold increase in IL-18 mRNA and elevated the levels of the pro-IL-18 protein. The levels of the precursor, p45, and the active subunit p10 peptides of the IL-18-processing enzyme, IL-1beta-converting enzyme (ICE), showed no substantial differences in all the conditions tested. IL-1beta was not detected under these experimental conditions. These data demonstrate that the production of IL-18 in the adrenal cortex is stimulated by ACTH treatment and is not inhibited by the direct action of corticosterone. In contrast to the anti-inflammatory action of GCs, IL-18 may have an immunostimulatory role during acute stress.

Adrenal Cortex↗

[Lipid peroxidation in the adrenal cortex during exhausting stress].

Under prolonged stress which is connected with exhaustion of functional resources of adrenal cortex the activation of lipid peroxidation processes in this gland was found. It is possible that the reason for such lipid peroxidation activation is the decrease in the content of adrenal cortex ascorbic acid and alpha-tocopherol.

11-Hydroxycorticosteroids↗

Circadian rhythm in c-fos protein expression in the rat adrenal cortex.

The circadian variation in the expression of c-fos protein(s) in the adrenal cortex of adult rats was investigated immunocytochemically. The animals were maintained in standard laboratory facilities with a 12:12 h light:dark schedule (07.00-19.00 h) until sacrificed. The number of c-fos immunoreactive (c-fos IR) cells was statistically constant in the zona fasciculata and zona reticulata at 20.00 h and 24.00 h, and 04.00 h, but was decreased to 52% at 08.00 h and to 18% at 12.00 h, respectively, when compared to the 24.00 h value. At 16.00 h, the number of c-fos IR cells was increased again to 63% of the 24.00 h value. In the zona granulosa c-fos IR was observed only at 20.00 h and 24.00 h. Administration of dexamethasone, a potent inhibitor of ACTH release, significantly reduced the number of c-fos IR cells. As the circadian rhythm of c-fos expression in the adrenal cortex correlates to that reported for ACTH secretion from the pituitary, the results suggest that c-fos gene is involved in mediating physiological ACTH-induced responses in the adrenal cortical cells.

Adrenal Cortex↗

Importance of the adrenal cortex for development and maintenance of hypertension in spontaneously hypertensive rats.

Adrenal regeneration following complete bilateral adrenalectomy in spontaneously hypertensive rats (SHR) was used to study the significance of glucocorticoid and mineralocorticoid hormones for the development and maintenance of hypertension. Pre-hypertensive (5 weeks of age) and hypertensive (10 and 16 weeks of age) male SHR underwent adrenalectomy (ADN) and were kept on 0.9% NaCl. The rats were ether stressed at various intervals to assess adrenal steroid production. Following ADN of all three age groups the development or maintenance of hypertension depended on the presence of adrenal regenerates. Animals without signs of adrenal regeneration remained or became normotensive. There was a significant correlation between plasma corticosterone levels following ether stress and blood pressure. Aldosterone and corticosterone production of regenerates and of adrenal cortex of intact SHR was studied in vitro. Under basal condition and following ACTH stimulation both tissues produced similar amounts of corticosterone, however considerably less aldosterone was secreted by regenerates. Betamethasone substitution in adrenalectomized rats caused a dramatic increase of blood pressure which was attenuated by L-propranolol. Aldosterone had no significant effect on blood pressure. It is concluded that glucocorticoids play a permissive role in the development of hypertension presumably via alteration of sympathetic neurotransmission.

Adrenal Cortex↗

A distinctive cell contact in the rat adrenal cortex.

Extensive cell contacts which resemble septate junctions occur between cells in the three major zones of the rat adrenal cortex. Characteristically, they extend between small intercellular canaliculi and the periendothelial space, frequently interrupted by gap junctions and rarely by desmosomes. Zonulae occludentes have not been identified in the adrenal cortex. Along this distinctive cell contact, the cell membranes of apposing cells are separated by 210-300 a bisected by irregularly spaced 100-150-A extracellular particles which are often circular in profile. In lanthanum preparations, these particles appear to form a continuous chain throughout the intercellular space and are visualized as an alveolate structure in sections parallel to the plane of the cell membrane. The cell membrane in the area of septate-like contact does not differ from nonjunctional areas of the cell membrane in freeze-fracture replicas. The cell contact retains its integrity after cell dispersion and after the separation of cell membranes from disrupted cells. The intercellular particles also persist after brief extraction in lipid solvents. Besides adherence, possible functions of this adrenal contact include maintenance of the width of the extracellular space, the provision of channels between intercellular canaliculi and the bloodstream, and utilization as cation depots. Similar structures are also present between adrenal cortical cells of several other species and between interstitial cells of the testis. This type of cell contact may, in fact, be a typical feature of steroid-hormone-secreting tissues in vertebrates.

Adrenal Cortex Hormones↗

Differentiation of the fetal adrenal cortex of rats--its experimental observation in vivo.

The development and tissue differentiation of the adrenal cortex of rats were studied by giving experimental treatments to the fetus in vivo. A low-ACTH-condition was given to the fetus by administrating Dexamethasone through its mother, or directly into the subcutaneous tissue of the fetus, or by decapitation, brain aspiration or hypophysectomy. When the fetus was given the low-ACTH-condition for the last 5 days or more, the hypoplastic adrenal cortex developed specifically. It had nearly normal zona glomerulosa (ZG), and poorly differentiated zona fasciculo-reticularis (ZF-R) without differentiated ZF-R. The observing day was settled at 21 1/2 days old. The shorter the period of low-ACTH-condition was, the more thickened the differentiated zone (ZF-R) grew. On the contrary, the poorly differentiated layer became thinner in proportion to the period of low-ACTH-condition. The poorly differentiated cortical cell had ACTH-reactivity. It seems that the development and tissue differentiation of the ZF-R depend on fetal own ACTH, and poorly differentiated cortical cells appear below the ZG, and differentiate by ACTH and were gradually pushed inside. The zona glomerulosa develops and differentiates without dependence of ACTH.

3-Hydroxysteroid Dehydrogenases↗

[Insensitivity of purified glutathione reductase from adrenal cortex to o,p'-dichlorodiphenyldichloroethane].

The activity of partially purified glutathione reductase (EC 1.6.4.2) was studied as affected by 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane (o,p'-DDD, chloditane). The glutathione reductase from human and dog adrenal cortex was purified by means of precipitation with (NH4)2SO4, by affinity chromatography, sephadex G25, DEAE-cellulose and CM-cellulose chromatography. A 56.6- and 41-fold purification was obtained for the enzyme from human and dog adrenal cortex, respectively. o,p'-DDD did not influence the activity of purified glutathione reductase in vitro. The rate of NADPH oxidation by adrenal cortex cytosol in the glutathione reductase reaction increased under the effect of o,p'-DDD.

Adrenal Cortex↗

[Comparative study of several structuro-functional parameters of the liver and adrenal cortex in mice of different genetic strains under physiologically normal conditions].

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.

11-Hydroxycorticosteroids↗

Cholesterol side-chain cleavage and 11 beta-hydroxylation are inhibited by gossypol in adrenal cortex mitochondria.

Cholesterol side-chain cleavage and 11 beta-hydroxylation were assessed in isolated adrenal cortex mitochondria by formation of pregnenolone and corticosterone, respectively, in the presence and absence of gossypol. Pregnenolone biosynthesis was inhibited when increasing concentrations of gossypol were added. The control value of 4 nmol min-1 mg-1 dropped to 2 nmol min-1 mg-1 with 30 microM of the drug in the incubation medium. A more pronounced inhibitory effect was observed upon 11 beta-hydroxylation of steroids; I50 was 11 microM. Seventy-five percent of corticosterone production was impaired when 30 microM of gossypol were present. Bovine serum albumin prevented and reversed the inhibitory action of the drug. Kinetic studies showed a linear mixed type inhibition, suggesting a direct action of the drug upon the enzymatic complex. This study demonstrates a direct inhibitory effect of gossypol upon the steroidogenic enzymes located in the inner mitochondrial membrane of the adrenal cortex.

Adrenal Cortex↗

Interleukin-1 beta, but not IL-1 alpha, stimulates cell proliferation in the adrenal cortex.

Endocrine and immune systems are closely interconnected, so the effect of interleukin-1 on adrenal cortex proliferation in vivo was investigated. Interleukin-1 alpha (IL-1 alpha) and IL-1 beta (0.1, 1 and 10 micrograms/kg) were given twice daily alone or in combination with interleukin-1 receptor-antibody (IL-1rAb) to adult male Wistar rats. The cell proliferation ratio was measured by 5-bromo-2'-deoxyuridine (BrdU) incorporation. BrdU-positive cells were counted in entire equatorial sections of the gland, and, in addition, separately for each adrenocortical zone. IL-1 beta (1 and 10 micrograms/kg) enhanced cell growth in the adrenal cortex. This was due to the stimulation of cell proliferation in the zona glomerulosa and fasciculata. IL-1rAb exerted an opposite effect, and reversed the stimulatory influence of IL-1 beta. IL-1 alpha did not evoke any significant changes in the proliferation ratio of the adrenocortical cells. The results indicate a close interconnection between the immune and endocrine systems with IL-1 beta providing a growth-promoting stimulus to adrenocortical cells.

Adrenal Cortex↗

Distribution of 3 beta-hydroxysteroid dehydrogenase during development of the rat adrenal cortex and capsule.

Fibroblasts of the adult adrenal cortex are considered to be nonsteroidogenic connective-tissue cells. However, it has been reported that in response to regenerative stimuli, adrenocorticotropic hormone (ACTH), and transformation to malignancy, these cells acquire characteristics of parenchymal cells, which includes delta 5, 3 beta-hydroxysteroid-dehydrogenase (delta 5, 3 beta-HSD) activity. To determine whether such delta 5, 3 beta-HSD activity in adult adrenocortical fibroblasts was due to the activation or augmentation of gene expression normally occurring during embryogenesis, a histochemical study of adrenocortical development, with particular attention to the connective-tissue capsule, was undertaken. Cryostat sections of rat embryos, from 14-days postconception (PC) to birth, and of adrenal glands 1-8, 44 and 90 days after birth were tested histochemically for delta 5, 3 beta-HSD. The same or adjacent sections were stained for PAS-positive material and reticulin, and with hematoxylin and eosin. delta 5, 3 beta-HSD activity overlapped with fibroblast-like cells and with extracellular connective-tissue components in the periphery of the glands from day-17 PC onward. delta 5, 3 beta-HSD activity over the capsule diminished shortly after birth and was absent in the adult. Appropriate controls showed that the staining within the capsule was specific and not an artifact. 3 beta-HSD activity in the capsule was more intensive when dehydroepiandrosterone (DHEA) was replaced by etiocholan-3 beta-ol-17-one (ETIO) as the steroid substrate. Furthermore, the spatial distribution of 3 beta-HSD activity in the cortex differed depending on the substrate used, and the distribution patterns changed with developmental age. (ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗

Studies on the compensatory growth of the adrenal cortex of the male hamster after unilateral adrenalectomy.

The aim of the study was to investigate the cellular aspects of compensatory growth of the adrenal cortex of male hamster after unilateral adrenalectomy. Relative right adrenal gland weight was higher at 24 h after hemiadrenalectomy with no differences--if compared with sham operated hamsters--at 12, 48, 96 and 120 h. In vitro 3H-thymidine incorporation per mg of adrenal after 12 h was higher and 120 h lower in monoadrenalectomised male hamsters than in sham operated animals with no differences in the remaining time-points studied. If 3H-thymidine incorporation was expressed per entire gland, only 120 h after surgery the uptake was lower than in sham operated animals. Five days after hemiadrenalectomy an increase in the average volume of the zona fasciculata cell and no change in the glomerulosa and reticularis zones were observed. At that day solitary adrenal cortex contained similar number of parenchymal cells as the right adrenal gland of sham operated animals. Thus, hemiadrenalectomy in the male hamster leads to a prompt proliferative response of the contralateral gland at 12 h after surgery, followed by decreased proliferative activity at 120 h after surgery. Monoadrenalectomy increased average volume of the zona fasciculata cell and did not change the total number of parenchymal cells in the gland if compared with sham operated animals.

Adrenal Cortex↗