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The influence of cobalt/vitamin B12 deficiency as a "stressor" affecting adrenal cortex and ovarian activities in goats.

Twenty 1.5 to 2-year old goats were made vitamin B12 deficient by feeding them cobalt-deficient diets for 23 weeks in order to determine the effects of a progressive deficiency on ovarian and adrenal cortex activities. At 1-day intervals, blood samples were collected for haematological study and plasma for vitamin B12, progesterone and corticosteroid radioimmunoassays. At 23 weeks, the adrenal cortex was taken for histological measurement and the pituitary gland and corpus luteum for LH and progesterone determinations, respectively. The regularity of the oestrous cycles was studied using teaser bucks. The goats receiving a cobalt-deficient diet presented irregular oestrous cycles (22.6 +/- 0.8 days; maximum deviation: 12 to 38 days), while those of the controls were 18 +/- 0.3 days (maximum deviation: 16 to 21 days). Low vitamin B12 concentration led to macrocytic and normochromic anaemia. The concentration of plasma progesterone augmented, but it decreased during the third and subsequent cycles in cobalt-deficient goats as compared to the controls. Plasma corticosteroids were persistently high in cobalt-deficient goats as compared to the controls, and pituitary LH was low in the deficient goats. It is suggested that an erratic endocrinological control mechanism led to irregular cycles, the action site being located in the hypothalamo-pituitary axis.

Adrenal Cortex↗

[Activity of neurohormonal hypothalamus-adrenal cortex axis in the course of transplantable mouse leukemia L1210].

The activity of the neurohormonal hypothalamus-adrenal cortex axis in the course of transplantable mouse leukemia L1210 was investigated. The secretory activity of the arcuate nucleus producing CRF, the fascicular zone of adrenal cortex secreting glicocorticosteroids and nucleus supraopticus hypothalami producing vasopressin was estimated with the karyometric method. Four groups of mice killed in various stages of cancerous process's advance were used. It was demonstrated that rapidly developing cancer is a considerable stress, which is proved by the increase in the neurohormonal axis activity in comparison to the control groups. The activity of the hypothalamo-adrenal axis was typical for a stress reaction: a two-phase process with a considerable increase in activity in the introductory phase of the developing leukemia and a visible decrease in the last phase, typical for an unspecific reaction, where no more effective mobilization for adaptation and activation of mechanisms is possible. The production of vasopressin has similar progress to other glands investigated, which suggests its stimulating influence on activation of the pituitary-adrenal axis. The statistical analysis of karyometric measurements was carried out by the Student's t test.

Adrenal Cortex↗

Morphohistochemical relationships between adrenal cortex and major salivary glands in response to chronic suramin treatment.

Adult male albino rats received 18 mg/kg i.p. of suramin twice a week, comparable to the human therapeutic situation. Sacrifices took place after 30 and 60 days of treatment. Adrenal cortex and major salivary glands were examined, using morphological and histochemical methods, in order to obtain a) confirmation of adrenocortical damage reported previously and b) original data for the major salivary glands. In rats the submaxillary gland in particular has already been found to be closely related to the functional conditions of the adrenal cortex. In all organs examined, alterations already evident in 30 day-treated rats, were constantly more marked and widespread in 60 day-treated animals. At the end of the treatment the adrenal cortex showed morphological (poor differentiation of the zona glomerulosa, hypertrophic cell clusters in the zona fasciculata) and histochemical (different distribution of neutral lipids, cholesterol and delta 5-3 beta-hydroxysteroid dehydrogenase) changes. Damage (vacuolizations, lymphocytic infiltrates) observed in major salivary glands was shown to be more marked and widespread in the submaxillary gland, confirming its functional dependence on adrenocortical activity.

3-Hydroxysteroid Dehydrogenases↗

Opposite effects of dexamethasone and ACTH on the adrenal cortex response to ethane dimethanesulphonate (EDS).

Recently we have reported that ethane dimethane-sulphonate (EDS), the Leydig cell cytotoxin, caused marked atrophy of the adrenal cortex of adult male rats. The aim of this work was to examine whether a 9-day treatment with dexamethasone (0.25 mg/kg/d) or ACTH (40 IU/kg/d), which started 4 days prior to administration of a single dose of EDS (75 mg/kg), influenced the response of the inner adrenocortical zones to the toxin. On day 15 after administration of EDS, adrenal weight was significantly decreased in saline treated rats, but glandular and serum corticosterone levels were not altered. In dexamethasone-suppressed rats, the effect of EDS was augmented; an additional decrease in adrenal weight was accompanied by reduced adrenal and serum corticosterone levels. In ACTH-treated animals EDS was ineffective. These results demonstrate that the deleterious effects of EDS on rat adrenal cortex can be prevented by ACTH and potentiated by dexamethasone.

Adrenal Cortex↗

Progesterone serum levels during the follicular phase of the menstrual cycle originate from the crosstalk between the ovaries and the adrenal cortex.

BACKGROUND: The preovulatory rise of progesterone is important for ovulation, but both its regulation and its origin are controversial. Three experiments were performed to determine whether follicular phase progesterone arises from the ovary, the adrenal cortex or both. METHODS: The first study was performed in patients scheduled for assisted reproduction, who received a long-acting GnRH agonist either during intake of an oral contraceptive or during the luteal phase of an otherwise untreated menstrual cycle. The second study was also performed during down-regulation with a GnRH agonist: some patients with elevated progesterone levels received dexamethasone (DXM). Others with similarly elevated basal progesterone levels and those with low progesterone levels were not treated with DXM and served as controls. Finally, adrenocorticotrophic hormone (ACTH) tests were performed in normocyclic volunteers both during early and late follicular phase and during intake of a contraceptive pill. RESULTS: During the suppression of endogenous gonadotrophin secretion progesterone levels rose after the administration of ACTH, but not of GnRH. DXM did not prevent the preovulatory rise of the serum progesterone concentration. The ACTH-stimulated concentration of progesterone and of 17alpha-hydroxyprogesterone were significantly reduced during intake of ethinyl estradiol. CONCLUSIONS: Progesterone arises in the adrenal cortex during most of the follicular phase, whereby its function is modulated by an unknown ovarian factor, which is suppressed by ethinyl estradiol. The source of progesterone shifts towards the ovaries prior to ovulation.

Adrenal Cortex↗

Distribution of prothymosin alpha in rat and human adrenal cortex.

BACKGROUND: Prothymosin alpha (ProT) is a polypeptide widely distributed in the organism and expressed by cell types with a high proliferative capacity. The aim of the current work was to investigate if ProT was localized in the progenitor compartment of the adrenal cortex which, following the cell migration theory, corresponds to the zona glomerulosa. METHODS: We studied by immunohistochemical and in situ hybridization methods the distribution of ProT in rat and human adrenal cortex. Immunohistochemical techniques for the study of the proliferating cell nuclear antigen (PCNA) and incorporation of 5-bromo-2'-deoxyuridin during DNA synthesis were also done. Immunoelectron microscopic procedures were performed to determine the exact subcellular localization of ProT. RESULTS: ProT was found in the zona glomerulosa cells, but not in the cells of the remaining cortical layers (zonae fasciculata and reticularis). Glomerulosa cells showed immunostaining for ProT only in the nuclei, excluding the nucleoli. Variability in immunostaining intensity was found between different glomerulosa cells. In situ hybridization of ProT mRNA confirmed that ProT synthesis in adrenal cortex occurs only in the zona glomerulosa. The results obtained for proliferating cell nuclear antigen and incorporation of 5-bromo-2'-deoxyuridin confirmed that adrenocortical proliferation occurs in the zona glomerulosa. Ultrastructural immunocytochemistry showed labelling for ProT over the euchromatin, but not on the heterochromatin aggregations nor the nucleoli. CONCLUSIONS: The results presented here: 1) support the migration theory for the adrenocortical cell renewal, 2) demonstrate that ProT is present in the nuclei of proliferating cells (being associated with euchromatin), and 3) suggest that the study of ProT expression would be useful in distinguishing cycling from resting cells.

Adrenal Cortex↗

Cushing's disease coexisting with a single macronodule simulating adenoma of the adrenal cortex.

A rare case of Cushing's disease coexisting with a single macronodule simulating adenoma of the adrenal cortex is presented. The basal and dynamic tests supported the diagnosis of Cushing's disease, whereas the CT-scan, ultrasound and iodocholesterol uptake were suggestive of a left adrenal adenoma. Treatment consisted of extirpation of the nodular gland followed by pituitary irradiation. The examination revealed a single macronodule with no histological membrane, surrounded by hyperplastic adrenocortex. Together with the three similar ones reported in the literature this case suggests that nodular hyperplasia may be an intermediary stage between diffuse hyperplasia and the appearance of an autonomous adenoma after long-term stimulation of the hyperplastic gland.

Adenoma↗

Localization of alkaline and acid phosphatases in healthy human adrenal cortex. Light and electron microscopic study.

Localization of alkaline and acid phosphatase activity was investigated in healthy human adrenal cortex by light and electron microscopy. The activity of both was found in the inner part of the adrenal cortex--mainly in the reticular zone. The reaction products of alkaline phosphatase were observed along the plasma membrane and those of acid phosphatase were observed mainly in the lysosomes and secretory vacuoles. The heavier deposit of phosphatase reaction products in the reticular zone may be explained by the fact that the reticular zone is most active in the steroidogenesis of glucocorticoid and adrenal androgen.

Acid Phosphatase↗

Adenylate cyclase activity and cyclic AMP production in the outer and inner zones of the adrenal cortex.

It has been reported that cells isolated from the inner zone of the guinea pig adrenal cortex fail to have a steroidogenic response to ACTH. To further explore this, adenylate cyclase activity of membrane particles and cAMP production by cells prepared from the inner and outer adrenocortical zones were determined. The cAMP response to ACTH and forskolin was similar for cells from both zones. Basal adenylate cyclase activity was significantly higher in the inner zone; and while absolute responses to ACTH, GppNHp, GTP, NaF, and forskolin were greater for the inner zone, relative responses were similar for the two zones. These observations suggest that the inner zone of the guinea pig adrenal cortex may have a defect in ACTH action at a step(s) beyond cAMP formation.

Adenylyl Cyclases↗

Regional distribution of microsomal drug and steroid metabolism in the guinea pig adrenal cortex.

The regional distribution of steroid and drug metabolism was studied in intact cells and microsomal fractions obtained from the chromatically distinct inner (zona reticularis) and outer (zona fasciculata plus zona glomerulosa) zones of the guinea pig adrenal cortex. Cells isolated from the outer cortical zone produced far more cortisol than cells from the inner zone and cortisol production was stimulated by adrenocorticotropic hormone only in cells from the outer zone. Among the factors which may contribute to the greater cortisol production by the outer zone are a higher rate of 17 alpha-hydroxylation and ratio of 17 alpha- to 21-hydroxylase activities in that zone, both of which favor cortisol synthesis. In contrast, steroid 21-hydroxylase activity was far greater than 17 alpha-hydroxylase activity in microsomes obtained from the inner zone of the adrenal cortex. Microsomal metabolism of various xenobiotics such as benzo(a)pyrene and ethylmorphine proceeded far more rapidly in the inner than outer cortical zone. The zonal differences in metabolism appeared to result in part from differences in the ability of xenobiotics to interact with microsomal cytochromes P-450 in the two zones. The results indicate that the inner zone has a minor role in cortisol production by the adrenal cortex, but its involvement in the production of other steroids cannot be excluded. In contrast, the inner zone appears to have the major role in the metabolism of at least some xenobiotics which may account for its greater vulnerability to the toxic effects of chemicals requiring metabolic activation.

Adrenal Cortex↗

Expression of vascular endothelial growth factor and its receptors Flk-1 and Flt-1 during the regeneration of autotransplanted adrenal cortex in the adrenalectomized rat.

PURPOSE: Autotransplantation of the adrenal cortex may be a therapeutic alternative in the future. For successful adrenal transplantation revascularization is necessary. It is possible that vascular endothelial growth factor (VEGF), which is a potent angiogenic peptide, may have some roles in adrenal transplantation through 2 its receptors, kinase insert domain-containing region (Flk-1) and fms-like tyrosine kinase (Flt-1). Therefore, we studied sequential changes in expression of VEGF, Flk-1 and Flt-1 in regenerated adrenal. MATERIALS AND METHODS: Eight to 9-week-old male Wistar rats underwent bilateral adrenalectomy and immediate adrenal capsular autotransplantation. The expression of VEGF, Flk-1 and Flt-1 was analyzed by immunohistochemistry and reverse-transcriptase-polymerase chain reaction. RESULTS: Angiogenesis was observed in the remodeling of adrenal sinusoidal endothelium during adrenal regeneration. Reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that VEGF expression increased in grafted tissue with time after transplantation and its Flk-1 receptor, which localized to endothelial cells, increased transiently during the regeneration process. Immunostaining for Flt-1 receptor was identified in adrenocortical cells and its intensity gradually increased during adrenal regeneration. CONCLUSIONS: During adrenal gland regeneration VEGF and its receptors Flk-1 and Flt-1 are thought to be involved in neovascularization.

Adrenal Cortex↗

Maturity of the adrenal cortex in very preterm infants is related to gestational age.

To study the maturity of the adrenal cortex in preterms born before 33 wk of gestation, basal levels of cortisol and cortisone and the cortisol and 17-hydroxyprogesterone (17-OHP) response to 1 microg/kg adrenocorticotropic hormone stimulation were measured in 24 appropriate-for-gestational age preterm infants (26-33 wk; 690-1985 g). Gestational age influenced the response of cortisol, 17-OHP, and the ratio between cortisol/17-OHP in the studied infants. In preterms born <30 wk of gestation, levels of cortisol, and the ratio between cortisol/17-OHP were lower compared with preterms born between 30 and 33 wk. Levels of cortisone were higher in preterms born <30 wk, suggesting a lower activity of 11 beta-hydroxysteroid dehydrogenase that may be related to maturity as well. These findings indicate that the adrenal cortex function in preterm infants is closely related to the duration of gestation and may be important in neonatal morbidity.

17-alpha-Hydroxyprogesterone↗

The distribution of vasoactive intestinal peptide in the rat adrenal cortex and medulla.

There is increasing evidence for the role of the autonomic nervous system in the control of adrenal cortical function although the nature of the innervation is as yet unknown. In view of our expanding knowledge of the roles which peptidergic putative transmitters play in the autonomic nervous system, the present study was adrenal gland. Using immunocytochemical methods, VIP was found distributed in fibers in the adrenal cortex and medulla. VIP fibers were found primarily in the capsule and zona glomerulosa of the cortex and in small bundles in the medulla and appeared to innervate the parenchymal cells in both cases. Both colchicine pretreatment and ligation of the splanchnic nerve resulted in an increase in staining of fibers of the cortex and the medulla. Demedullated adrenals (regenerated) exhibited a reduced number of VIP fibers in the zona glomerulosa. It appears that the medullary and at least part of the cortical VIP fibers originate in the medullary VIP cell bodies which are regulated by the splanchnic nerve. The distribution of VIP suggests an important role for this peptide in both adrenal cortical and medullary function and a possible medullary modulation of adrenal cortical function.

Adrenal Cortex↗

Deoxycorticosterone, 11 beta-hydroxylase and the adrenal cortex.

We report a child in whom DOC excess secondary to congenital adrenal hyperplasia (CAH, 11 beta-hydroxylase deficiency) caused malignant hypertension. Clinical and metabolic control could be achieved only by replacement of both glucocorticoid and mineralocorticoid, thus confirming in clinical practice the hypothesis that DOC is produced from both the zonae fasciculata and glomerulosa of the adrenal cortex under the independent control of the ACTH and renin-angiotensin systems respectively.

Adrenal Cortex↗