In vitro studies of nuclear volume of rat adrenocortical cells: lace of ACTH effect

The effect of ACTH on nuclear volume of adrenocortical cells in the zona fasciculata of rat adrenal cortex was examined in vitro. Sections of adrenal gland were incubated for 60 or 90 min in Krebs-Ringer's solution with 1% glucose in the presence of ACTH, actinomycin D, cycloheximide and aminoglutethimide. ACTH, despite its clear effect in stimulating steroidogenesis, did not exert a direct effect on the nuclear volume of cells studied. This phenomenon is not dependent upon the stimulation of steroidogenesis, since aminoglutethimide does not influence the nuclear volume of adrenocortical cells studied; rather, ACTH in the presence of aminoglutethimide leads to a decrease in their volume. Actinomycin D does not influence nuclear volume while after incubation with cycloheximide nuclei were larger than the control. The presence of ACTH did not alter this effect. These results indicate no relationship between the degree of corticosterone output and nuclear volume in rat adrenocortical cells of the zona fasciculata in vitro.     

Modulation of the renin-angiotensin system may alter the adrenocortical regeneration

The effect of the renin-angiotensin system on adrenocortical regeneration has been studied in rats subjected to left adrenal enucleation combined with contralateral adrenalectomy. It was found that angiotensin II stimulated both proliferation and the steroidogenic capacity of the regenerating adrenal cortex cells by 6 days after operation. The stimulatory effect of angiotensin was prevented by losartan, a type 1 angiotensin (AT1) receptor antagonist, and by nifedipine, a calcium channel blocker. Losartan and nifedipine also depressed the adrenocortical regeneration when given alone. Enalapril, an angiotensin converting enzyme blocker, inhibited both the proliferation and steroidogenesis of the regenerating adrenal cortex, but this effect could be prevented by angiotensin II.     

Co-secretion of aldosterone and cortisol by an adrenocortical carcinoma

We report a rare case of adrenocortical carcinoma. A 26-year-old woman presented with hypokalemia and hypertension due to hyperaldosteronism. She had no signs of Cushing's syndrome. Endocrinological data showed excess of aldosterone production and nonsupressible cortisol production on 2 mg of dexamethasone. Magnetic resonance imaging showed left adrenal tumor. Transabdominal left adrenalectomy was performed and histopathological diagnosis was adrenocortical carcinoma. Her blood pressure and hypokalemia returned to normal after adrenalectomy. There is no recurrence after 36 months. We want to emphasis the importance of adrenal tests before the operation even if there are no signs of excess cortisol production.     

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.     

Compensatory increase in adrenomedullary angiotensin-converting enzyme activity (kininase II) after unilateral adrenalectomy

Angiotensin-converting enzyme (ACE, kininase II, dipeptidyl carboxypeptidase, EC 3.4.15.1) was characterized in the adrenal medulla of male Sprague-Dawley rats. Rat adrenal medulla and lung ACE were similar in their susceptibility to Cl- activation and to the inhibition by EDTA, captopril, bacitracin and thiorphan, suggesting that rat adrenal medulla and lung ACE have similar properties. Changes in right adrenal weight and in adrenomedullary ACE activity 5 and 12 days following left unilateral adrenalectomy (UADX) were examined. Compensatory adrenocortical hypertrophy 12 days following UADX was associated with a significant increase in adrenal medullary ACE activity. This change was due not to a modified affinity of ACE for the substrate but to an alteration in ACE maximal velocity or number of available molecules. UADX had no effect on adrenocortical ACE activity. When UADX was combined with right splanchnic denervation, the increase in adrenomedullary ACE activity was blocked. The results support the existence of a functional ACE in adrenal medulla that is under neuronal control.     

Nuclear bodies in the normal and hyperfunctional human adrenal cortex

Adrenal pieces obtained from six female patients, three without increased adrenocortical function and three with Cushing's disease, showed, in all adrenal cortex zones, cells containing simple and complex nuclear bodies. The simple nuclear bodies were spherical or ovoid and had a filamentous structure surrounded by a clear halo. Complex nuclear bodies were more numerous and heterogeneous in patients with adrenal pathology, and they were spherical with a proteinaceous filamentous capsule surrounding a core; the core was granular, filamentous or a mixture of granular and filamentous material, sometimes with a reticular or concentric arrangement. Some bodies showed vacuolar or multilocular aspect, and others had a close relationship with the nucleolus or appeared near the interchromatin granules. The meaning of adrenal nuclear bodies is discussed as well as their relationship with ACTH stimulation.     

Expression of glucocorticoid receptor isoforms in human adrenocortical adenomas

Introduction

Glucocorticoid receptor (GR) is expressed in the normal human adrenal gland, however, no study has been performed to evaluate the separate expression of α- and β-isoforms (GRα and GRβ) in normal human adrenals and in adrenocortical adenomas.

Experimental

GRα and GRβ mRNA expression was examined by quantitative real-time PCR in 31 adrenal tissues including 19 non-functioning adenomas (NFA), 6 cortisol-producing adenomas (CPA) and 6 normal adrenocortical tissues. In addition, the presence and cellular localization of GRα and GRβ proteins in adrenal tissues were studied by immunohistochemistry.

Results

Compared to normal adrenocortical tissues, both GRα and GRβ mRNAs were significantly increased in CPA but not in NFA. Using anti-GRα antibody a strong nuclear staining was observed in NFA and CPA, and a less remarkable immunoreactivity was detected in some nuclei of normal adrenocortical cells. GRβ immunostaining was absent in normal adrenal tissues and NFA, while a strong cytoplasmic and nuclear immunoreaction was found in CPA.

Conclusions

Altered expression of GRα and GRβ in CPA raises their possible role in the pathophysiology of these adrenal tumors, although further studies are needed to elucidate the potential significance of these findings.     

Melatonin-induced suppression of the pinealectomy-stimulated rat adrenal cortex mitotic activity

Pineal involvement in the regulation of adrenocortical mitotic activity has recently been suggested. It has been shown that melatonin (Mel) decreased the mean mitotic activity rate (MMAR) of the adrenal cortex both in vivo and in organ culture. The goal of the present study was to test the influence of pinealectomy (PX) and/or Mel-treatment on the MMAR of adrenocortical cells, as well as on the adrenal weight in rats. The stathmokinetic method was used in the study. It was found that PX significantly increased the MMAR of the adrenocortical cells. Moreover, Mel suppressed the proliferogenic effect of PX on the rat adrenocortical cells. Melatonin alone did not significantly affect the mitotic activity of the adrenal cortex. None of the three experimental procedures, i.e. Mel, PX and Mel-treatment of pinealectomized animals significantly affected the adrenal weight. The present data suggest that Mel may be involved in the inhibitory control of adrenocortical cell proliferation.     

Studies on lipoprotein and adrenal steroidogenesis: I. Roles of low density lipoprotein- and high density lipoprotein-cholesterol in steroid production in cultured human adrenocortical cells

The roles of human low density lipoprotein (LDL)- cholesterol and high density lipoprotein (HDL)- cholesterol on adrenal steroidogenesis were investigated using cultured human adult and fetal adrenocortical cells and the findings were then compared to those obtained with bovine adrenocortical cells. The secretion of cortisol in both human and bovine adrenocortical cells was dose-dependently increased by the administration of LDL- or HDL-cholesterol in the presence of adrenocorticotropin (ACTH). LDL-cholesterol was utilized to a greater extent than HDL-cholesterol in both human and bovine adrenal steroidogenesis in the presence of ACTH. Exogenous lipoprotein-derived cholesterol was less utilized in human adrenal steroidogenesis than in bovine adrenal steroidogenesis, compared to the endogenous cholesterol. An increase in the secretion of cortisol and dehydroepi androsterone sulfate (DHEA-S) continued for the 5-day culture period, in the presence of lipoprotein cholesterol and ACTH in both human adult and fetal adrenocortical cells. The secretion of aldosterone increased on the first day of the culture period, then gradually decreased for the 5-day culture period in human adult adrenocortical cells, but not in human fetal adrenocortical cells in the presence of lipoprotein cholesterol and ACTH. These findings demonstrate that exogenous cholesterol utilized in the biosynthesis of steroids is mainly from LDL-cholesterol in both human adult and fetal adrenals and bovine adrenal and the proportion of cholesterol synthesized de novo is significantly larger in the human adult adrenal than in the bovine adrenal.     

A case of glucocorticoid-suppressible hyperaldosteronism with aldosterone producing adenoma

A 34-yr-old woman with hypertension (142/102 mmHg), hypokalemia, high plasma and urinary aldosterone and low plasma renin activity was studied. A left adrenal tumor and enlarged right adrenal gland were demonstrated by adrenal venography. During administration of dexamethasone (2 mg daily, for 3 weeks), urinary aldosterone excretion decreased abruptly from 22.5 to 9-11 micrograms/day, serum potassium increased and blood pressure fell to 120-130/80-90 mmHg. After left adrenalectomy, all manifestations improved with no medication. The resected adrenal gland revealed clear cell adenoma and micronodular adrenocortical hyperplasia. The patient was considered to be a rare case of glucocorticoid-suppressible hyperaldosteronism with an aldosterone-producing adenoma.     

Evidence of 11 beta-hydroxylase deficiency in a patient with cortical adrenal adenoma

We explored a 61 year old woman with mild hirsutism. An adrenal tumor was found in the left adrenal, which was held responsible for the androgen secretion. The in vitro incubation of the tumor tissue showed an impaired 11 beta-hydroxylation of 11-deoxycortisol. This is a rare and unusual case of adrenal pathology showing that a deficiency in 11 beta-hydroxylase activity does not rule out the presence of an adrenocortical adenoma.     

Retroperitoneal adenoma

The authors describe a tumor localized next to the left adrenal gland. On histological examination the lipid-rich tumor was found to be partly a solid adrenocortical adenoma and partly a tubular oncocytoma.     

Effect of ACTH on mitochondrial RNA synthesis of rat adrenocortical cells

Summary The incorporation of 3H-thymidine and 3H-uridine into adrenocortical cells of intact and ACTH-treated rats was investigated by high-resolution autoradiography. The quantitative analysis of autoradiographs shows no effect of ACTH on the incorporation of 3H-thymidine, at least in our experimental conditions. On the contrary, ACTH was found to enhance the incorporation of 3H-uridine into both adrenocortical nuclei and mitochondria. These findings are discussed in relation to numerous biochemical and morphological data, indicating that ACTH stimulates the synthesis of enzymes and structural proteins of adrenocortical cells.It is suggested that the mechanism of action of ACTH on adrenal cortex, consists in an integrated stimulation of both nuclear and mitochondrial DNA-dependent RNA synthesis.The authors wish to express their sincere appreciation to Mrs. L. Rebonato and Mr. G. Gottardo for skilled technical assistance.     

Pheochromocytoma associated with adrenocortical adenoma: case report and literature review

The case of a 60-year-old woman with pheochromocytoma and concomitant adrenocortical adenoma in the same gland is presented. She complained of episodic headache, palpitation, nausea, vomiting and sweating. Physical examination revealed that the patient has generalized obesity, wet skin and paroxysmal hypertension, but no signs of Cushing's syndrome. Elevated levels of urinary noradrenaline, adrenaline and total metanephrine were sequentially observed. In addition, urinary 17-OHCS was also slightly elevated, but plasma cortisol was normal and suppressed after oral administration of 0.5 mg of dexamethasone. Abdominal echography and CT scanning demonstrated a left adrenal tumor, which took up both 131I-meta-iodobenzylguanidine and 75Se-scintadoren in the same region. A left adrenalectomy was performed and the tumor was found to consist of two parts, pheochromocytoma (2.5 X 2.5 X 2.5 cm) and cortical adenoma (2.5 X 3 X 5 cm). A total of 23 reported cases showing evidence of hyperfunction of the adrenal cortex and the medulla were noted. So far as we know, this patient was the second case of pheochromocytoma with adrenocortical adenoma in Japan.     

Hypertrophy of the adrenal cortex

The human adrenal cortex in essential hypertension and in the salt-losing form of the adrenogenital syndrome and the adrenal cortex in spontaneously hypertensive rats were studied by morphometry. Under long-term functional loading hypertrophy of adrenocortical cells is the common way of increasing the mass of the cortex. The correlation between the morphological parameters of the adrenocortical structures increases in this condition. Hyperplasia along with hypertrophy has been found in man at an early age. The differences in the degree of hypertrophy of the nuclei and nucleoli may be connected with different intensity of adrenocortical function in different pathological conditions.