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PubMed1979

Alterations in adrenal growth and corticosteroid content in foetal and neonatal rats developing at high altitude.

To study the effects of chronic maternal hypoxia on the growth and functional development of foetal and neonatal adrenal glands, Long-Evans rats were acclimatized to high altitude (3800 m) before mating and were maintained at this height throughout gestation. The body growth of the progeny at high altitude was essentially normal during the perinatal period, but adrenal weight and adrenocortical function showed marked differences from those of control rats maintained at sea level. The adrenal glands were larger in foetuses but smaller in neonates, compared with the adrenal glands of control animals maintained at sea level. Differences in the protein content of the adrenal glands between the two groups paralleled differences in adrenal weight. The concentration and content of corticosterone in the adrenal glands of both foetuses and neonates kept at high altitude were markedly lower than values in animals kept at sea level. The lower adrenal corticosterone content was not reflected in the concentration of the hormone in the peripheral plasma, since this was essentially the same at high altitude and at sea level in both mothers and perinatal animals. The reduction in the adrenal corticosterone content was accompanied by and may have resulted from, a reduction in the concentration of cytochrome P-450 in the adrenal tissue of foetuses maintained at high altitude. Possible explanations for the dichotomous results are discussed.

Adrenal Cortex Function Tests↗

PubMedDate not supplied

Ultrasonographic characteristics of both adrenal glands in 15 dogs with functional adrenocortical tumors.

Ultrasonographic examination of both adrenal glands was performed in 15 dogs with functional adrenocortical tumors (FAT). Bilateral adrenal tumors were diagnosed in three of 15 dogs, and unilateral tumors were diagnosed in 12 of 15 dogs. Adrenal tumors were characterized by adrenal gland enlargement with loss of the normal shape and parenchymal structure. The contralateral adrenal gland could be imaged in all dogs with unilateral tumors. Based on size, shape, and parenchymal structure, the contralateral adrenal gland was similar to adrenal glands of normal dogs. The results of this study show that: 1) both adrenal glands should be imaged routinely in dogs with hyperadrenocorticism; 2) bilateral adrenocortical tumors seem to be more frequent than previously assumed; 3) one normal adrenal gland does not exclude the existence of a contralateral FAT; and 4) the functional atrophy of the contralateral adrenal gland in dogs with FAT may not be apparent ultrasonographically.

Adrenal Cortex Neoplasms↗

PubMed2000

[Progress in imaging diagnostics of adrenal neoplasms].

Computed tomography is the modality of choice in imaging of adrenal glands. Density measurements on images without contrast agent are essential for differentiation of adrenal masses. Application of spiral computed tomography for diagnostics of adrenal masses enables sensitive detection of small adrenal tumors and reliable density measurements by elimination of uneven breath-holds effect and minimization of partial volume effect. Tissue harmonic imaging in ultrasonography is a new technique, which enables visualization of abdominal parenchymal organs with higher tissue contrast with less artifacts and is especially useful in ultrasound imaging of difficult-to-image patients with high body weight. Further comparative research will enable to learn the advantages of using that technique in diagnostics of adrenal masses. Magnetic resonance imaging enables very accurate visualization diagnostics of adrenal masses. It is due to its inherent multiplanar imaging capabilities and high tissue contrast of soft tissues which enables very accurate visualization of anatomical structures in adrenal region. Introduction of new techniques of magnetic resonance imaging as chemical shift imaging and dynamic studies with paramagnetic contrast agent enables accurate differentiation of adrenal cortex adenomas from non-adenomas. In case of difficulties in adrenal diagnostics magnetic resonance imaging is often a problem solving examination in regard to other imaging techniques of adrenal region.

Adrenal Gland Neoplasms↗

PubMed2002

Adrenal lymphoma and Addison's disease: report of a case.

Addison's disease due to adrenal lymphoma usually manifests as bilateral adrenal enlargement. We report a patient with Addsion's disease in whom the initial overt primary adrenal insufficiency was accompanied by an only slightly enlarged right adrenal gland. The 80-year-old man presented with nausea, anorexia, weight loss, and hyperpigmentation of the skin and buccal mucosa. Addison's disease was diagnosed based on this clinical presentation and laboratory findings of low cortisol and high adrenocorticotropin levels. Computerized tomography (CT) of the adrenal glands revealed a small right adrenal tumor. His family refused to allow percutaneous or surgical biopsy to determine the nature of the tumor. His general condition improved after steroid supplementation. However, about 1 year later, dizziness, fever, night sweats, and edema of the lower legs developed, and adrenal CT scanning revealed that the left adrenal gland had enlarged and now exceeded the size of the right one. Left adrenalectomy was performed and pathology showed a diffuse large B-cell lymphoma. Staging work-up using whole-body CT scanning suggested a stage IIIb lymphoma. Chemotherapy was given, but the disease still progressed and the patient died 4 months after diagnosis. Primary adrenal lymphoma should be considered in the differential diagnosis of Addison's disease, even if only slight enlargement of the adrenal glands is found initially.

Addison Disease↗

PubMed1990

[CT findings in bilateral adrenal enlargement].

CT findings in ten patients with bilateral adrenal enlargement (six cases of adrenal metastasis, two cases of malignant lymphoma, one case of pheochromocytoma and one case of adrenal hemorrhage) reviewed. Four of six cases of adrenal metastasis showed asymmetrical adrenal enlargement on initial CT scans. Ring enhancement on postcontrast CT was recognized in one case of adrenal metastasis and one case of adrenal hemorrhage (subacute stage). Ring enhancement in the case of adrenal hemorrhage was more clear and smooth than that in the case of adrenal metastasis. One case of malignant lymphoma and one case of adrenal hemorrhage had Addison's disease.

Adrenal Gland Diseases↗

PubMed1998

CT findings of adrenal glands in patients with tuberculous Addison's disease.

The CT findings of adrenals in 18 cases of tuberculous Addison's disease are reported. All cases demonstrated bilateral adrenal involvement, 35 glands with active tuberculosis appeared enlarged and one with non-active tuberculosis showed an atrophic gland with calcification. Areas of non-enhancing necrosis in the enlarged adrenals were seen in 34 glands (17 cases), among them 19 glands showed peripheral rim enhancement. In the 35 enlarged adrenals 25 glands had preserved contours. Small calcification dots in the adrenals were seen in 7 glands with active tuberculosis (4 cases). The CT signs of active tuberculous adrenalitis associated with Addison's disease were enlarged glands associated with large necrotic areas, with or without dot-like calcification. When the contours of the adrenals were preserved, the diagnosis of infectious disease could be made with increased confidence. Tuberculous adrenalitis should not be excluded when the enlarged adrenal glands appear mass-liking. CT study of the morphological changes of adrenal glands on patients with Addison's disease might help to define the etiology of the disease and contribute to treatment planning.

Addison Disease↗

PubMed1984

Magnetic resonance imaging of the adrenal glands: a comparison with computed tomography.

This investigation compared magnetic resonance imaging (MRI) with computed tomography (CT) in the evaluation of normal and abnormal adrenal glands. Thirty normal volunteers were studied with MRI, and the results were compared with a retrospective review of 30 normal CT examinations. CT identified both adrenal glands in all 30 patients. MRI identified both glands in 29 of 30 volunteers. There were no statistically significant differences between the two imaging techniques using chi-square analysis. Twenty-one patients with abnormal adrenal gland(s) detected with CT were also studied with MRI. The abnormalities studied included bilateral hyperplasia (three patients), adenoma (two), myelolipoma (one), adrenal metastases (six), adrenal hemorrhage (two), and neuroblastoma (seven). MRI detected the abnormal adrenal gland(s) in 20 of 21 patients. MRI was unable to detect calcifications in the lesions studied but more clearly showed the relations of adrenal masses to the major vascular structures. MRI demonstrated corticomedullary differentiation in patients with adrenal hyperplasia and in some normal volunteers. The CT and MRI features of the adrenal lesions are discussed.

Adenoma↗

PubMed1991

Clinical significance of the solitary functioning adrenal gland.

To assess the compensatory functional and anatomic changes in the remaining adrenal cortex after unilateral adrenalectomy or in the unaffected adrenal in patients with unilateral adrenal destruction by neoplasm, 17 patients with a single, functioning adrenal gland and normal indices of adrenocortical function, nine after adrenalectomy and eight with a unilateral, destructive adrenal lesion were studied with 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy and computed tomography. Adrenal masses with a mean (+/- s.d.) diameter of 2.8 +/- 1.0 cm; (range 1-4 cm; 95% confidence interval (Cl), 2.5-3.1 cm) were identified by computed tomography in seven of nine patients in the remaining adrenal cortex at variable times (6.1 +/- 5.9 y; range 0.5-19 y) after unilateral adrenalectomy. Mean (+/- s.e.m.) NP-59 uptake was elevated (p less than 0.01) in both adrenalectomy and adrenal destruction groups, mean uptake (+/- s.e.m.) was 0.32% +/- 0.04% administered dose (95% Cl, 0.24%-0.4% administered dose) as compared to normal (0.16% +/- 0.05% administered dose, 95% Cl, 0.06%-0.26% administered dose). The remaining adrenal cortex may be anatomically abnormal after unilateral adrenalectomy and demonstrate compensatory, increased NP-59 uptake in the presence of overall, normal adrenocortical function.

Adosterol↗

PubMed1976

Angiotensin antagonists and the adrenal cortex and medulla.

Several analogs of angiotensin in which the phenylalanine in position 8 of the peptide chain was replaced by an aliphatic amino acid residue are specific antagonists of angiotensin in aorta, the adrenal medulla, and adrenal zona glomerulosa. In the adrenal cortex and medulla, all actapeptide analogs have more agonist activity than in aortic strips. In studies with N-terminally substituted analogs, it appears that adrenal degradation of the angiotensin molecule by aminopeptidase(s) does not occur or is not retarded by N-terminal mocifications such as sarcosine substitution. The decapeptide analog [Ile8]-angiotensin I and heptapeptide analog [des-Asp1, Ile8]-angiotensin II were excellent antagonists in the adrenal medulla and each peptide was devoid of intrinsic activity. These substituted homologs of angiotensin may offer a novel approach for the development of selective antagonists of angiotensin receptors. In the adrenal cotex, [des-Asp1, Ile8]-heptapeptide possessed greater receptor affinity than any of the angiotensin octapeptides studied. This C-terminally substituted heptapeptide does have significant intrinsic activity in the adrenal cortex which would limit the use of this compound as an antagonist of vascular responses to angiotensin II. In studies with [Ile8]-angiotensin II, [Sar1, Ile8]-angiotensin II, and [des-Asp1, Ile8]-angiotensin II, the pA2 values calculated indicate that the N-terminal residue is not important for receptor binding in the adrenal cortex but may be of significance in binding to adrenal medullary and aortic smooth muscle receptors. At the present time it appears unlikely that any single animal model or assay system can reliably predict the agoinst/antagonist activities of angiotensin analogs for all the various end organs which respond to the angiotensins.

Adrenal Cortex↗

PubMed1998

ADH1 and ADH4 alcohol/retinol dehydrogenases in the developing adrenal blastema provide evidence for embryonic retinoid endocrine function.

Studies on retinoid signaling indicate that much of the regulation of this pathway may involve enzymes that synthesize the active ligand retinoic acid. Alcohol dehydrogenases ADH1 (class I ADH) and ADH4 (class IV ADH) function as retinol dehydrogenases in the oxidation of retinol, a necessary step in the synthesis of retinoic acid from vitamin A. These enzymes as well as retinoic acid have previously been localized in the adult adrenal gland, thus providing evidence that this organ is an endocrine source of retinoic acid. Here, we have examined the involvement of ADH1 and ADH4 in embryonic adrenal function by using transgenic mouse technology and immunohistochemistry. Transgenic mice were generated that contain various portions of the mouse ADH4 promoter and 5'-flanking region fused to lacZ. Embryos harboring a construct containing 9.0 kb of 5'-flanking region displayed very high levels of lacZ expression in the developing adrenal blastemas at embryonic stage E11.5 during the initial phase of mouse adrenal gland development. The presence of endogenous ADH4 protein in stage E11.5 adrenal blastemas was demonstrated by immunohistochemistry, and this was the only site of ADH4 immunodetection in stage E11.5 embryos. Endogenous ADH1 protein was also detected by immunohistochemistry in stage E11.5 adrenal blastemas. ADH1 and ADH4 proteins were detectable at later stages of adrenal development, and both were localized to developing adrenal cortical cells by stage E14.5. The presence of both ADH1 and ADH4 retinol dehydrogenases during the earliest stages of adrenal gland development, combined with our earlier findings of high levels of retinoic acid in the embryonic adrenal gland, suggests that one of the earliest functions of ADH may be to provide an embryonic endocrine source of retinoic acid for growth and development.

Adrenal Glands↗

PubMedDate not supplied

Polymeric contrast agents for MR imaging of adrenal glands.

A variety of adrenal imaging agents have been used in nuclear medicine, but no agent has been developed for magnetic resonance (MR) imaging. The authors have previously observed accumulation of aminated macromolecules in adrenal glands. They now report the synthesis of a model polymeric aminated contrast agent for enhanced MR imaging of the adrenal glands. The model agent consisted of a poly-L-lysine conjugate (molecular weight, 245 kd) that had 70% free epsilon amino groups and 30% diethylenetriaminepentaacetic acid (DTPA)-derivatized amino groups to bind indium-111 or gadolinium. One hour after intravenous administration of this compound, adrenal uptake was 10.1% +/- 0.7 of injected dose per gram of tissue. When all free epsilon amino groups of the polylysine were completely substituted with DTPA, adrenal uptake was 3.4 times lower, indicating the importance of free amino groups for adrenal uptake. MR imaging in rats showed that a dose of 0.08 mmol of gadolinium per kilogram of the agent was sufficient to enhance the signal intensity of adrenal glands. There hours after intravenous administration of the agent, signal intensity of the adrenal glands was 186% of precontrast values (liver, 165%; kidney, 91%). Fluorescence microscopy showed that the agent accumulated primarily in the cortical zona glomerulosa and in the adrenal medulla. These initial studies demonstrate the feasibility of designing contrast agents for MR imaging of the adrenal glands.

Adrenal Glands↗

PubMed1998

Induction of CYP1A1, but not CYP1A2, in adrenals of 3, 3'-methylcholanthrene-treated guinea pigs.

To test the inducibility of CYP1A homologs in guinea pig adrenal, the effects of 3,3'-methylcholanthrene, an archetypal inducer of CYP1A, were compared in guinea pig adrenal and liver. Western blot analysis showed that levels of both CYP1A1 (53 kDa) and CYP1A2 (56 kDa) increasedin liver microsomes of 3,3'-methylcholanthrene-treated guinea pigs. In adrenals, an immunoreactive protein comigrating with liver CYP1A1 was detected only after 3,3'-methylcholanthrene treatment. Protein comigrating with CYP1A2 was never detected in adrenal microsomes. A third inducible immunoreactive protein (57 kDa) was seen in liver, but not adrenal, after 3, 3'-methylcholanthrene treatment. Another immunoreactive protein (52 kDa), present constitutively in liver and adrenal microsomes, was not induced in either tissue by 3,3'-methylcholanthrene. The precise identities of the inducible 57-kDa and the noninducible 52-kDa proteins remain to be determined. However, the identity of the 53-kDa protein in the adrenal as CYP1A1 was confirmed by RT-PCR, Northern blot, and sequence analysis. Similar analyses demonstrated that, despite the fact that the 56-kDa protein was not detectable in adrenal microsomes, CYP1A2 mRNA was present in adrenals of control animals. Strikingly, CYP1A2 mRNA decreased in adrenal, but increased in liver, following 3,3'-methylcholanthrene treatment, underscoring differences in the regulation of CYP1A expression in the two tissues. Levels of ethoxyresorufin and methyoxyresorufin metabolism correlated with levels of CYP1A1 and CYP1A2 protein, respectively.

Adrenal Glands↗

PubMed1993

Evidence for an increased catecholamine synthesis in rat adrenal glands following stimulation of peripheral dopamine receptors.

In studies on peripheral dopamine (DA) turnover in our department evidence has accumulated that changes in adrenal DA levels induced by varying degrees of neurogenic stimulation roughly reflect changes in the catecholamine (CA) synthesis rate. The question arises if changes in DA levels in rat adrenals induced by different DA D-2 receptor agonists and previously reported from our laboratory, also indicate changes in CA synthesis. After various periods of drug administration rats were killed by decapitation and tissue CA levels in adrenals and forebrain were determined by HPLC-EC. The potent inhibitor of DA-beta-hydroxylase FLA 63 (40 mg/kg i.p.) increased adrenal DA by 186% after 1 h and by 423% after 3 h. The DA D-2 agonist quinpirole (0.2 mg/kg s.c., 30 min) itself increased adrenal DA by 55-60% compared to control. In FLA 63 pretreated rats quinpirole increased adrenal DA levels by further 127% (FLA 63-1 h), resp. 122% (FLA 63-3 h) than did FLA 63 itself. The DA D-2 receptor antagonist domperidone (3 mg/kg s.c., 150 min) blocked the quinpirole effect both in saline and FLA 63 (3 h) pretreated rats. Adrenal DOPAC was changed in similar manner as adrenal DA in FLA 63 pretreated rats. No significant changes either in adrenal NA or A were observed after FLA 63 pretreatment. Under the present experimental conditions adrenal DA may thus mainly be looked upon as an intermediate in the synthesis of NA and A, and the elevation of DA induced by DA D-2 receptor stimulation as a consequence of increased catecholamine synthesis.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Comparative analysis of plasma 17-hydroxyprogesterone and cortisol responses to ACTH in patients with various adrenal tumors before and after unilateral adrenalectomy.

Patients with non-hyperfunctioning adrenal adenomas often have an increased plasma 17-hydroxyprogesterone response to ACTH stimulation. The effects of adrenal surgery on this abnormality have rarely been investigated. One hundred and sixty-one patients with unilateral adrenal tumors (non-hyperfunctioning adenomas, 78; cortisol-producing adenomas, 8; aldosterone-producing adenomas, 37; adrenal cysts, 12; pheochromocytomas, 26) were studied. Patients before and after adrenal surgery as well as 60 healthy subjects underwent an ACTH stimulation test using 2 mg synthetic ACTH(1-24) (Cortrosyn Depot, Organon). Basal and ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol concentrations are reported. Before adrenal surgery, the basal plasma 17-hydroxyprogesterone concentrations were normal in patients with all types of tumors. However, the ACTH-stimulated plasma 17-hydroxyprogesterone levels were abnormally increased in 53% and 31% of patients with non-hyperfunctioning adenomas and aldosterone-producing adenomas, respectively. In addition, a few patients with adrenal cysts and pheochromocytomas also showed an increased ACTH-stimulated 17-hydroxyprogesterone response. After unilateral adrenalectomy, this hormonal abnormality disappeared in most, although not all patients with adrenal tumors. In patients with non-hyperfunctioning adrenal tumors, ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol concentrations significantly correlated with the size of the tumors. These results firmly indicate that the tumoral mass itself may be responsible for the increased plasma 17-hydroxyprogesterone and cortisol responses after ACTH stimulation in patients with non-hyperfunctioning and hyperfunctioning adrenal adenomas.

17-alpha-Hydroxyprogesterone↗

PubMed2002

Adrenal involvement in multiple endocrine neoplasia type 1.

Adrenal lesions belong to the spectrum of multiple endocrine neoplasia type 1 (MEN-1) syndrome. However, the prevalence of adrenal involvement, the characteristics, and the clinical management of adrenal lesions have not yet been clearly defined. A total of 66 patients with confirmed MEN1 germline mutations and 1 additional patient with typical manifestations in three organ systems were monitored in a regular screening program that included evaluation of the adrenals (median follow-up 96 months; range 12 to 300 months). Age at the diagnosis of MEN-1 and of adrenal tumors and the clinical characteristics, genotype, treatment, and follow-up of adrenal disease were analyzed. Adrenal lesions were identified in 18 of 67 (26.8%) MEN-1 patients and were diagnosed 5 years later than MEN-1. The median tumor diameter at diagnosis was 3.0 cm (range 1.2-15.0 cm), with most tumors being 3 cm or smaller. Eight patients had bilateral tumors. Ten patients had nonfunctional benign tumors, three had benign adrenal Cushing syndrome, and one patient had a pheochromocytoma. Four patients developed adrenocortical carcinomas (ACCs), three of which were functional. Nine adrenalectomies and one subtotal adrenalectomy were performed in six patients. Three patients with ACC died owing to the tumor. Patients with mutations in exons 2 and 10 developed adrenal tumors significantly more often than patients with other mutations (p <0.01). Adrenal tumors are a common feature of MEN-1 but occur later in the course of the disease. The lesions are often small and nonfunctional and can therefore be managed by close surveillance; others have significant malignant potential and should be considered for surgery when they are 3 cm or larger.

Adolescent↗

PubMed1999

MEN I gene mutations in sporadic adrenal adenomas.

Loss of heterozygosity (LOH) on chromosome 11q13 occurs in about 20% of sporadic adrenal neoplasms. Adrenal lesions, mostly benign, occur in up to 40% of patients from MEN I kindreds. The MEN I gene, positioned on 11q13, has been considered a primary candidate gene in these lesions. We studied a group of 15 patients with sporadic adrenal adenoma, and 1 patient with multinodular hyperplasia. Of the 16 patients, 4 had incidentally discovered masses, 5 had Conn's syndrome, 6 suffered from Cushing's syndrome, and 9 had high sex hormone production. Studies with the markers D11S480, PYGM, D11S449, and D11S987 in 13 patients (12 of whom were from our group of 16) revealed 4 losses of heterozygosity on D11 S480 on 11q13, but the deletion did not affect the MEN I gene in any case. We present complete direct DNA sequencing data of the menin gene in 14 sporadic adrenal adenomas and one with adrenal hyperplasia. We identified one heterozygous missense mutation, T552S, in a hormonally inactive adrenal adenoma. One base exchange was identified close to the intron-exon boundary in intron 9 of a nodular adrenal hyperplasia. mRNA expression studies found that MEN I was transcribed in all 13 samples analyzed. In summary, our study identified the second patient with sporadic benign adrenal tumor presenting a menin gene mutation. Our complete direct sequencing approach adds evidence that menin gene mutations may account only for a minority of benign adrenal tumors if at all. Another tumor-suppressor gene inactivated in sporadic adrenal neoplasms may be located on chromosome 11q13.

Adenoma↗

PubMed1993

Transvaginal ultrasonographic measurements of the fetal adrenal glands at 12 to 17 weeks of gestation.

OBJECTIVE: Our purpose was to compile normative data of fetal adrenal gland measurements between 12 and 17 weeks' gestation with transvaginal ultrasonography. STUDY DESIGN: Transvaginal ultrasonographic measurements of the fetal adrenal length and adrenal-to-kidney length ratio calculations were performed on 100 normal fetuses at 12 to 17 weeks' gestation. The diameters of the fetal adrenals and kidneys on each side were measured, and nomograms were generated. These parameters were also measured in two fetuses whose mothers were treated for congenital adrenal hyperplasia. RESULTS: The measurements of the maximal longitudinal axis of the right and left fetal adrenal glands showed a linear increase with fetal age between 12 and 17 weeks of gestation. The adrenal-to-kidney length ratio decreased linearly between these gestational ages. In maternal congenital adrenal hyperplasia treated with glucocorticosteroids the fetal adrenals were small. CONCLUSION: Fetal adrenal gland measurements in the early second trimester show a linear progressive growth between 12 and 17 weeks' gestation.

Adrenal Glands↗

PubMed1995

Inactivation of adrenal cytochromes P450 by 1-aminobenzotriazole. Divergence of in vivo and in vitro actions.

Recent investigations demonstrated that administration of 1-aminobenzotriazole (ABT) to rats caused adrenal gland enlargement. Studies were done to pursue the mechanism(s) involved. Preliminary experiments revealed that the adrenal enlargement caused by ABT was associated with a decline in plasma corticosterone concentrations, suggesting inhibition of adrenal steroidogenesis. Indeed, a single injection of ABT (25 or 50 mg/kg body weight) to rats caused concentration-dependent declines (60-80%) in adrenal mitochondrial and microsomal cytochrome P450 (P450) concentrations. The decreases in adrenal P450 levels exceeded those in hepatic microsomes. Accompanying the declines in adrenal P450 concentrations were decreases in steroid hydroxylase activities. Mitochondrial 11 beta-hydroxylase and cholesterol side-chain cleavage activities and microsomal 21-hydroxylase activity were diminished markedly (60-90%) by ABT treatment. In contrast, activity of adrenal 3 beta-hydroxysteroid dehydrogenase-isomerase was not affected by ABT, indicating specificity for P450-dependent reactions. Incubation of adrenal microsomes or mitochondria in vitro with ABT plus an NADPH-generating system had no effect on P450 concentrations or on steroid hydroxylase activities. Similar incubations with hepatic microsomes caused declines in P450 levels and in the rates of P450-mediated xenobiotic metabolism. The results demonstrate that ABT is a potent inhibitor of adrenal steroid hydroxylases in vivo, but the in vitro studies indicate that the mechanism of action differs from that on other P450 isozymes. The absence of inhibitor effects in vitro suggests that an extra-adrenal metabolite of ABT is responsible for the in vivo inactivation of steroidogenic enzymes.

Adrenal Glands↗