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[The morphofunctional characteristics of the zona glomerulosa of the adrenal cortex in rats with hereditary stress-induced arterial hypertension].

Morphometrical analysis of adrenal cortex glomerular zone performed in rats with hereditary stress-induced arterial hypertension assisted in establishing important peculiarities of the zone structure. Adrenocorticocytes of adrenal cortex glomerular zone in hypertension rats are subjected to hyperplastic intercellular changes, suggesting the increase of the zone functional activity, which is substantiated by data on significantly high aldosterone concentration in plasma of these animals.

Aldosterone↗

[Functional morphology of the adrenal cortex during the physiological rhythm of sex steroid synthesis].

A method of a quantitative histenzymological analysis was used for determination of the extent of participation of various zones of the adrenal cortex in provision of physiological rhythm of the steroid synthesis. The activity of 3beta-OH-steroid dehydrogenase, glucoso-6-phosphat dehydrogenase, NAD- and NADP-diaphorases, acid and alkaline phosphatases and non-specific esterase was investigated. The data of a histoenzymotological study were compared with the result of biochemical analysis of corticosteroids in the peripheral blood. Under physiological conditions intensification of steroidogenesis was realized by mobilization of individual groups of cells of the adrenal gland, not its whole parenchyma. Physiological rhythm of steroid synthesis was provided by an integrated function of all the zones; however, by duration and quantitative expression of the secretory activity a structural heterogeneity was revealed in the adrenal cortex.

11-Hydroxycorticosteroids↗

Differential activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in zones of the adrenal cortex.

Cholesterol metabolism and steroidogenesis in the outer (zona fasciculata/glomerulosa) and inner (zona reticularis) zones of the adrenal cortex were examined in the guinea pig. It is known from previous studies that the content of cholesterol in the inner zone is considerably lower than that in the outer zone, although basal low density lipoprotein (LDL) receptor activity is similar in the two zones. To further explore cholesterol metabolism in the guinea pig adrenal cortex, the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting step in cholesterol synthesis, has been examined for which this paper forms the initial report. It was found that the basal specific activity of HMG-CoA reductase was similar in the outer and inner adrenocortical zones (approximately 230 pmol mevalonate formed/min X mg microsomal protein). The administration of ACTH caused 4- and 5-fold increases in HMG-CoA reductase activity in the outer and inner zones, respectively. In fact, the increase in HMG-CoA reductase activity with ACTH treatment was always greater for the inner zone than for the outer zone. This is in contrast to LDL receptor activity, which does not increase in the inner zone as it does in the outer zone with ACTH treatment. When dexamethasone was administered, HMG-CoA reductase activity decreased in the outer zone by about 50%, while there was no change in reductase activity in the inner zone. The latter finding is similar to what happens with LDL receptor activity during dexamethasone administration. Why suppression of endogenous ACTH had no effect on HMG-CoA reductase activity in the inner zone while exogenous ACTH administration caused a marked increase in enzyme activity is not clear, but may be related to phosphorylation/dephosphorylation mechanisms. Based on the use of sodium fluoride in solutions to block HMG-CoA reductase phosphatase, evidence is presented which indicates that a pharmacological dose of ACTH alters the phosphorylation/dephosphorylation status of HMG-CoA reductase in the inner adrenocortical zone, but not in the outer cortical zone.

Adrenal Cortex↗

Allogeneic adrenocortical transplantation: glucocorticosteroid-independent immunomodulatory properties of adrenal cortex cells.

BACKGROUND: Hormone substitution for the treatment of adrenocortical insufficiency does not adequately substitute the physiologic circadian secretion of corticosteroids and leads to long-term sequelae and reduced quality of life. The lack of adaptation to physical and psychologic stress situations may lead to life-threatening Addison's crises. Allogeneic transplantation of adrenal cortex could offer an intriguing alternative. Adrenocortical grafts were demonstrated to proliferate and produce corticosteroids in physiologic concentrations after transplantation. METHODS: K -transgenic murine lymphocytes and allogeneic adrenal cortex cells were cocultured in mixed lymphocyte reactions to examine the alloimmune response; lymphocytes from T-cell receptor transgenic mice and normal mice, respectively, served as responder cells. The effects of corticosteroids secreted by adrenocortical cells were antagonized by the steroid receptor antagonist mifepristone, whereas the impact of cell-cell interactions was differentiated with transwell culture systems. RESULTS: Coculture of adrenal cortex cells in mixed lymphocyte reactions markedly suppressed lymphocyte proliferation. Transwell cultures demonstrated that adrenocortical cells exerted their effects by a soluble factor that was only partially antagonized by mifepristone. CONCLUSION: In vitro, the presence of adrenocortical cells potently suppressed allogeneic immune responses. This effect was not exclusively the result of the secretion of corticosteroids, indicating an additional immunomodulatory property of adrenocortical cells.

Adjuvants, Immunologic↗

Steroidogenesis in the zona glomerulosa of the adrenal coretx. I. Isolation and some properties of mitochondria from the zona glomerulosa of the bovine adrenal cortex.

Isolation procedures for mitochondria from the zona glomerulosa of the bovine adrenal cortex are described and the properties of the mitochondria thus prepared are compared with those isolated from the zona fasciculoreticularis. The cristal membranes of mitochondria in the zona glomerulosa in situ are tubular or tubulovesicular, whereas those of mitochondria in the zona fasciculoreticularis in situ are vesicular. When mitochondria are isolated from the former zone, they invariably showed the condensed configuration regardless of isolation media, whereas those isolated from the latter zone in an ST medium showed the orthodox configuration. When Ca2+ was added to mitochondria isolated either from the zona glomerulosa or the zona fasciculoreticularis in an STE medium in the condensed configuration, a transition from the condensed to the orthodox configuration tool place; the cristal membranes of mitochondria from the zona glomerulosa became tubular or tubulovesicular and those of mitochondria from the zona fasciculoreticularis became vesicular. Contaminations of mitrochondria of the zona glomerulosa with other cellular organelles were examined using various marker enzymes. There was no difference in cytochrome content between mitochondria of the two zones specified above. The coupling efficiency of mitochondria of the zona glomerulosa was found to be remarkably effected by temperature during the isolation procedures. Effects of various substrates, isolation media, and bovine serum albumin on the coupling efficiency of mitochondria of the zona glomerulosa are also described.

Adrenal Cortex↗

Origin and identity of adrenocortical tumors in inhibin knockout mice: implications for cellular plasticity in the adrenal cortex.

Inhibin knockout (Inha-/-) mice develop gonadal sex-cord tumors and--when gonadectomized--adrenocortical tumors. Previous reports demonstrated that adrenocortical tumors from Inha-/- mice produce estrogen and depend on gonadotropin signaling for initiation. Here we show that, in addition to producing estrogen, the adrenocortical tumors display a global change in cellular identity, composed of two unique cell types expressing differing arrays of genes normally restricted to theca and granulosa cells of the ovary. Many of these genes are also induced in wild-type adrenals after gonadectomy or upon chronic gonadotropin stimulation, suggesting that the adrenal cortex normally contains a population of pluripotent cells that can be driven toward an adrenal or gonadal identity given the appropriate pituitary stimuli. A central feature of this altered cellular identity is the switch from predominant expression of Gata6 (endogenous to the adrenal cortex) to Gata4, which defines cellular identity in the ovary. We show that stable transfection of Gata4 in cultured adrenocortical cells is sufficient to activate ovarian-specific genes of both theca and granulose lineages. Spatial analysis of Gata4 expression reveals a distinct pattern of localization to the supcapsular region of the adrenal, which contains undifferentiated progenitor cells that continuously populate the adrenocortical zones. Although both wild-type and Inha-/- mice display this pattern, only Inha-/- mice produce tumors composed of these Gata4-positive cells. These data suggest that Inha-/- adrenocortical tumors cells are derived from pluripotent adrenocortical progenitor cells that adopt a gonadal fate due to the convergent loss of inhibin and chronic exposure to elevated gonadotropins.

Adrenal Cortex↗

[Influence of qualitatively different diets on the reproductive capacity and function of the adrenal cortex in rats with experimental toxic hepatitis].

The effect of a diet rich in protein and the group B vitamins on the function of the ovaries and adrenal cortex, as well as on the reproductive capacity of animals with experimental affection of the liver produced by administration of carbon tetrachloride was studied on 115 mongrel albino female-rats. A high-standard semisynthetic diet devised at the Institute of nutrition of the AMS of the USSR and three isocaloric experimental diets calorifically enriched by 20, 50 and 100 per cent and containing a double amount of the group B vitamins were used in tests. The protein and vitamins enrichment of the diet, although failing to normalize the estrual cycle, neveretheless contributed to a significant reduction of the embryos' death in pregnant animals, the restoration of the reproductive capacity of the rats being directly proportional to the degree of the protein enrichment of the diet. The use of experimental diets helped normalize the adrenal cortex function in pregnant rats with toxic hepatitis, this manifesting itself in the falling amount of corticosterone in the blood serum outflowing from the suprarenals down to the control level.

Adrenal Cortex↗

[Virilizing tumours of the adrenal cortex with unimpaired menstruation (author's transl)].

Virilizing adenomas of the adrenal cortex entail, typically, hirsutism, amenorrhea and hypertrophy of the clitoris. We report two cases of adrenal adenoma, both revealed by hirsutism and significant biological features, but both without any alteration of the menstrual cycle. One of our 2 patients showed moderate hypertrophy of the clitoris. In the first patient, the tumour has been located thanks to dexamethasone--modifiying adrenal secretion, and in the second patient, thanks to angiography. These two cases reported are a warning never to neglect more hirsutism, even, when unobstrusive, and always to undertake minimal hormonal investigations.

Adenoma↗

Stereological studies on the effects of pinealectomy, melatonin and oestradiol on the adrenal cortex of ovariectomised rats.

The aim of the study was to examine by means of stereology the effects of pinealectomy and melatonin on the structure of the adrenal cortex of ovariectomised rats and to check whether the effect of oestradiol on the rat adrenal cortex is modified by the pineal gland. Neither pinealectomy (73 days) nor melatonin treatment (10 micrograms/day for 17 days) changed the absolute and relative weights of adrenal glands of ovariectomised rats or the volumes of individual adrenocortical zones. The average volume of the zona fasiculata cell was higher in pinealectomised than in control rats; adrenal glands of all groups studied contained a similar number of adrenocortical cells. Oestradiol (two injections of estradiol cypionate) resulted within 22 days in a marked increase in adrenal weight, associated with an increase in the total number of parenchymal cells in the cortex of the gland; however, the average volume of adrenocortical cells was unchanged. Neither pinealectomy nor melatonin replacement treatment modified oestradiol effects on the gland. The results cast doubt on the role of the pineal gland and of its principal hormone, melatonin, in influencing adrenocortical structure in the rat and reveal that the pineal gland does not modify oestradiol effects on the gland.

Adrenal Cortex↗