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At least 685 records · Page 38Linked to original sources
PubMed1989

Gas chromatographic and gas chromatographic/tandem mass spectrometric characterization of precursors on the sesterterpene pathway for steroid biosynthesis.

An increasing amount of evidence is accumulating to support the proposal that steroidogenesis can occur by a sesterterpene pathway as well as the cholesterol pathway. Key intermediates on the sesterterpene pathway are 23,24-dinor-5-cholen-3 beta-ol (guneribol) and some of its metabolites, e.g. 23,24-dinor-4-cholen-3-one (guneribone). It has been reported that these intermediates are biosynthesized and converted to steroid hormones by a range of endocrine tissues in vitro. Monitoring the pentafluorobenzyloxime derivatives by negative ion chemical ionization mass spectrometry in the electron capture mode provided evidence for the presence of guneribone in extracts of bovine testicular and human adrenal tumour tissue. Complementary evidence was obtained from gas chromatographic/tandem mass spectrometric data generated on a triple-quadrupole instrument by monitoring daughter ions (in the multiple ion detection, MID mode) of the molecular anion of derivatized guneribone in both standards and tissue extracts. The present findings that sesterterpene pathway intermediates are present as endogenous compounds in tissue extracts, together with the previously reported radiochemical data, give further support to the sesterterpene pathway hypothesis.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Evaluation of adrenal masses with gadolinium enhancement and fat-suppressed MR imaging.

A study was undertaken to determine the ability to characterize benign and malignant masses with unenhanced and contrast material-enhanced fast low-angle shot and fat-suppressed spin-echo magnetic resonance (MR) imaging. Thirty patients with adrenal masses detected at computed tomography (CT) underwent MR imaging within 14 days after CT. CT and MR images were interpreted in a prospective, blinded fashion. Sixteen patients had 20 benign adrenal masses, and 14 patients had 18 malignant masses. Quantitative measurements included percentage of contrast enhancement on immediate postcontrast dynamic images and periphery--center signal-to-noise ratio (S/N) on gadolinium-enhanced fat-suppressed images. Qualitative evaluation included determination of the regularity of lesion margins, homogeneity of signal intensity, and local extension. MR imaging depicted all adrenal masses discovered at CT examinations. Lesions ranged in diameter from 1 to 15 (mean, 4.4) cm. No significant difference was observed in percentage of contrast enhancement between benign (90.5% +/- 59.0 [standard deviation]) and malignant (110.5% +/- 116.4) masses. A difference was observed between periphery--center S/N for benign (-.05 +/- 1.5) and malignant (7.7 +/- 9.8) masses; overlap between the two, however, occurred. Qualitative evaluation allowed correct characterization of 32 of 38 masses, comparing favorably with CT, which allowed characterization of 30 lesions.

Adenoma↗
PubMedDate not supplied

MR demonstration of a cystic pheochromocytoma.

Cystic pheochromocytoma is a rare tumor of the adrenal gland that can pose a diagnostic challenge. We report a case of a 14-year-old boy who had an adrenal lesion that appeared cystic by both sonography and CT, but that demonstrated hemorrhage into the lesion at MR imaging, and proved to be a cystic pheochromocytoma. We emphasize the importance of considering the diagnosis of pheochromocytoma when faced with a cystic lesion of the adrenal gland.

Adolescent↗
PubMed2004

Adrenal lesions with heterogeneous suppression on chemical shift imaging: clinical implications.

PURPOSE: To investigate the frequency and significance of adrenal lesions that demonstrate heterogeneous suppression on chemical shift magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective search of adrenal lesions identified on MR from November 1997-July 2001 was performed. The adrenal lesions were classified as having suppression typical for an adenoma, nonsuppression, or atypical heterogeneous suppression. Lesions with heterogeneous suppression were further reviewed. Follow-up for the heterogeneous lesions consisted of imaging studies or pathology from surgical excision. RESULTS: Adrenal lesions were identified in 242 patients. Heterogeneously suppressing lesions were seen in 34 (14%) patients. Several different patterns of heterogeneous suppression were identified. Imaging or pathologic follow-up was available for 18 of the heterogeneously suppressing lesions (one patient had both). Fifteen patients with follow-up imaging showed stability of the lesion over a significant interval, suggesting a benign lesion. Pathology was available for four patients revealing two patients with adenomas and two patients with nodular hyperplasia. Thus, all 18 patients with heterogeneous suppression had a benign lesion. CONCLUSION: Adrenal lesions that have a heterogeneous pattern of suppression on out-of-phase chemical shift MR images are a common finding. Our small series suggest that these lesions are probably benign.

Adenoma↗
PubMed1990

Rat dopamine beta-hydroxylase: molecular cloning and characterization of the cDNA and regulation of the mRNA by reserpine.

A number of cDNA clones for rat dopamine beta-hydroxylase (DBH) were isolated from a rat pheochromocytoma tumor cDNA library. The 2445 nucleotide sequence revealed a single open reading frame of 1860 nucleotides and a 3' untranslated region containing two polyadenylation addition signals. The cDNA coded for a 620 amino acid protein of 69,883 daltons. Six potential glycosylation sites and one potential phosphorylation site were identified. Amino acid residues likely to be involved in the active site of DBH and in copper ligand binding were identified. The N-terminal 42 amino acids appeared to constitute a typical but unusually long signal sequence. Hydropathy analysis indicated that this N-terminal region contained the only extensive hydrophobic domain and thus constituted the only obvious potential membrane attachment site. Northern analysis detected two mRNA species of 2.5 and 2.7 kb. The relative abundance of the 2.7 vs. 2.5 kb mRNAs was differentially regulated in PC12 cells and adrenals. DBH mRNA levels were induced in vivo in rat adrenals upon treatment with reserpine.

Adrenal Gland Neoplasms↗
PubMed1994

The genomic organization and functional analysis of the promoter for the human angiotensin II type 1 receptor.

We have cloned and characterized several human angiotensin II type 1 receptor (hAT1R) cDNAs by utilizing the 5'-RACE procedure. Sequence analysis demonstrated that human AT1 receptors are encoded by at least four distinct mRNA transcripts sharing an identical open reading frame, but differing in their organization of 5'-untranslated sequences. Therefore, even though multiple alternatively spliced forms of hAT1R mRNA are transcribed, they are all translated into identical receptors since the entire open reading frame of this receptor is harbored on a single exon. None of these exons coding for 5'-untranslated sequence is expressed in a tissue specific manner. By comparing the 5'-RACE cDNA clones with our hAT1R genomic clones, the organization of the hAT1R gene was determined. The human AT1 gene is comprised of at least four exons and spans at least 60 kb. Several putative promoter regions were characterized by utilizing primer extension and luciferase reporter gene constructs transfected into human adrenal cells. These results indicate that we have cloned a functional promoter for the hAT1R gene. Furthermore, this promoter harbors an adrenal specific response element.

Adenocarcinoma↗
PubMed1995

Expression of the endothelin-converting enzyme gene in human tissues.

Based on the cDNA sequence of the human and bovine endothelin converting enzyme (ECE-1) we have developed a novel reverse transcription polymerase chain reaction to investigate the tissue expression of this gene. We were able to specifically detect the gene mRNA starting from very limited amount of tissue in all human as well as bovine tissues examined. Thus, our results confirm a widespread expression of the ECE-1 gene in human tissues, in keeping with the findings in other species, and suggest a major biological role of ECE-1.

Adrenal Gland Neoplasms↗
PubMed1993

Plasma membrane cholesterol is utilized as steroidogenic substrate in Y-1 mouse adrenal tumor cells and normal sheep adrenal cells.

Previous studies from this laboratory indicate that plasma membrane cholesterol acts as an important source of steroidogenic substrate for MA-10 Leydig tumor cells. The present studies were designed to generalize these findings to other steroidogenic cells and to another species. Studies were performed using the Y-1 murine adrenal tumor cell line and primary cultures of sheep adrenocortical cells. Treating Y-1 cells with the acyl coenzyme A:cholesterol acyltransferase inhibitor, 58-035, caused cellular cholesteryl ester depletion and rendered more apparent the effect of dibutyryl-cAMP to cause cellular free cholesterol depletion. Radioactive 20 alpha-dihydroprogesterone was synthesized by Y-1 cells that had been plasma membrane-labeled with [3H]-cholesterol. Primary sheep adrenal cultures that had been cholesteryl ester-depleted also demonstrated cellular free cholesterol depletion after stimulation with dibutyryl cAMP. Plasma membrane label was converted to steroid hormones in these cells as well. Taken together, these data indicate that the use of plasma cholesterol is not restricted to the MA-10 cells. The present data indicate that both neoplastic mouse adrenal tumor cells and normal sheep adrenal cells utilize plasma membrane cholesterol.

Adrenal Gland Neoplasms↗
PubMed1996

Macronodular congenital adrenal hyperplasia in an adult with female pseudohermaphroditism.

We report a case of previously undiagnosed congenital adrenal hyperplasia presenting with virilisation in a 59-year-old woman. Biochemical analysis revealed C-21 hydroxylase deficiency. CT demonstrated adrenal hyperplasia and a 3.8-cm adrenal nodule, raising the possibility of the development of an autonomous adrenal adenoma or carcinoma. The adrenal nodule regressed significantly with oral replacement steroid therapy over the next 30 months, indicating it to be an ACTH-dependent hyperplastic nodule and thus avoiding the need for biopsy or surgical excision. Macronodular adrenal hyperplasia should be considered in the differential diagnosis of a patient presenting with virilisation and an adrenal mass.

Adenoma↗
PubMed1990

Genetic evidence for alpha 2-adrenergic receptor subtypes in rat brain, heart and adrenal gland.

A complementary DNA (cDNA) clone - cA2-47 - corresponding to a new alpha 2-adrenergic receptor subtype has been isolated from a rat brain cDNA library and used as a hybridization probe to scrutinize the alpha 2-receptor poly(A+) RNAs in rat brain, heart and adrenal gland. Hybridization of the 5' half of the coding region of this cDNA at 37 degrees C to rat brain poly(A+) RNA revealed a single band at 5.8 kb as the size of its corresponding mRNA. Under identical hybridization conditions, a human platelet alpha 2-receptor genomic probe failed to hybridize to any rat brain mRNAs. Under lower stringency conditions, hybridization of the full-length cDNA, cA2-47, to selected rat tissue poly(A+) RNA showed the presence of four different sized mRNAs in brain and three in both heart and adrenal gland. Messages of 1.3 kb and 2.1 kb were common in all three tissues (although the band at 2.1 kb was slightly higher in the heart and adrenal gland). A 5.8 kb mRNA was unique to the brain and a slightly higher band at 6.0 kb was consistently present in heart and adrenal gland but was absent in the brain. A fourth message at 3.4 kb was found predominantly in the brain and was either absent or present at very low levels in the other tissues examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1994

Primary aldosteronism: difference in clinical presentation and long-term follow-up between adenoma and bilateral hyperplasia of the adrenal glands.

Since 1974 primary aldosteronism has been diagnosed in 71 patients in our outpatient clinic. Thirty-four patients had a unilateral aldosterone-producing adenoma, whereas bilateral adrenal hyperplasia was diagnosed in 37 patients. Although at the time of diagnosis the mean potassium values were lower and mean aldosterone levels were higher in patients with an adenoma, as compared to those with bilateral hyperplasia, these laboratory data did not allow us to differentiate between the two leading causes of primary aldosteronism in the individual patient due to pronounced overlap of laboratory values between the two groups. During the first few years, a successful differential diagnosis was made by adrenal phlebography and separate sampling of plasma aldosterone in both adrenal veins; later non-invasive imaging techniques such as computed tomography and radionuclide scanning were used. The best results were obtained in patients with adenoma who underwent adrenalectomy. Fifty-six percent of these patients were clinically and biochemically cured; 28% were improved and had normal blood pressure values during drug treatment. In contrast, patients with bilateral hyperplasia were treated pharmacologically, but only in half of the patients could normal blood pressure values be achieved. Two thirds of the male patients developed gynecomastia during spironolactone treatment. As expected, unilateral adrenalectomy was unsuccessful in the 7 patients with bilateral hyperplasia who underwent surgery. Our results confirm that surgical treatment of adrenal adenomas and drug treatment of bilateral hyperplasias are the appropriate therapy in primary aldosteronism. A differential diagnosis cannot be made on the basis of clinical and non-invasive laboratory data alone; imaging techniques have to be included in the diagnostic process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1985

o,p'-DDD (mitotane) treatment for Cushing's syndrome: adrenal drug concentration and inhibition in vitro of steroid synthesis.

o,p'-DDD is an inhibitor of adrenal steroid synthesis currently used for therapy of Cushing's syndrome. Conflicting data have been published on the relationship between the plasma level of the drug and its clinical and biological effects. The levels of o,p'-DDD and o,p'-DDE in various tissues obtained from treated patients have been measured and are compared with data on in vitro steroidogenesis in adrenal tissues from the same patients. o,p'-DDD was found in all samples and o,p'-DDE in half of them, both levels being high when the tissue lipid concentration was high. There was considerable variability in lipid content from one tissue to another and within a tissue from one sample to another; only the drug to lipid ratio seems able to provide a reproducible index of drug entry into a tissue. No relationship was found between the tissue concentration of the drug and the total dose administered or inhibition of the steroid biosynthetic step studied.

17-alpha-Hydroxyprogesterone↗