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Biomedical subjects

C A Strott

Publications and source records attributed to C A Strott.

At least 55 records · Page 3Linked to original sources
PubMed1984

Cholesterol side-chain cleavage activity in the outer and inner zones of the adrenal cortex.

Cholesterol side-chain cleavage activity in mitochondria isolated from the outer and inner zones of the guinea pig adrenal cortex was evaluated in order to clarify the role of the zona reticularis in steroidogenesis. It was found that side-chain cleavage activity was three times higher in the outer zone. In addition, ether stress increased side-chain cleavage activity in the outer zone but not the inner zone. The concentration of total and free cholesterol was also found to be higher in the outer zone. However, when exogenous cholesterol was added to mitochondria, there was no enhancement in side-chain cleavage activity in either zone.

Adrenal Cortex↗
PubMed1984

Steroid concentrations in the outer and inner zones of the adrenal cortex of the guinea pig.

The outer (glomerulosa and fasciculata) and inner (reticularis) zones of the adrenal cortex of the guinea pig were separated and their steroid content determined. It was found that the concentration of 21-hydroxypregnenolone, deoxycorticosterone, corticosterone, aldosterone, 11-deoxycortisol, and cortisol was significantly higher in the outer cortical region, while the concentration of pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone was significantly higher in the inner zone. The concentration of progesterone, 17-hydroxyprogesterone, and androstenedione was not different in the two zones. Examination of specific steroid ratios suggested the following: (1) 3 beta-ol dehydrogenase/isomerase and 21-hydroxylase activities are reduced in the inner zone, (2) 17-hydroxylase and C17 20 lyase activities appear to be equally active in the two zones (3) 11 beta-hydroxylase activity appears to be more active in the inner zone (4) 21- hydroxypregnenolone , deoxycorticosterone, corticosterone, 11-deoxycortisol, and cortisol along with aldosterone are produced principally in the outer zone.

17-alpha-Hydroxypregnenolone↗
PubMed1984

Cortisol production by cells isolated from the outer and inner zones of the adrenal cortex of the guinea pig.

Cortisol production by cells isolated from the outer (glomerulosa and fasciculata) and inner (reticularis) zones of the adrenal cortex of the guinea pig was evaluated in order to clarify the steroidogenic function of the zona reticularis. Basal cortisol production by the outer zone cells was 5-10 times greater than that by the inner zone cells. Cells from the outer zone increased cortisol production in response to ACTH (ED50, approximately 33 pg/ml), while cells from the inner zone failed to respond to ACTH. Likewise, cells from the outer zone increased cortisol production in response to (Bu)2cAMP, while cells from the inner zone failed to respond. When either pregnenolone or progesterone was added to the incubation mixture, an increase in cortisol production by cells of the inner zone was noted, although the increase was significantly less than that observed for cells from the outer zone. These results suggest that the zona reticularis of the guinea pig adrenal ordinarily produces little or no cortisol, although the enzyme machinery is present and capable of producing a limited amount of cortisol when supplied with the appropriate precursor.

Adrenal Cortex↗
PubMed1984

Differential suppression of the outer and inner zones of the adrenal cortex of the guinea pig.

To examine the regulation of the zona fasciculata and the zona reticularis of the guinea pig adrenal cortex, animals were placed on a chronic regimen of dexamethasone. Changes in adrenal zonal weight, cholesterol side-chain cleavage activity, and tissue and serum steroid concentrations were measured after 1 month of dexamethasone administration. With dexamethasone treatment, the weight of the outer zone (glomerulosa/fasciculata) decreased significantly, while the weight of the inner zone (reticularis) did not change. Cholesterol side-chain cleavage activity in mitochondria isolated from the outer zone also declined significantly, while a similar activity in the inner zone did not change. The serum cortisol concentration in response to dexamethasone administration decreased by 85%, as did the concentrations of cortisol and progesterone in the outer zone; the concentration of cortisol in the inner zone decreased by only one third, while the concentration of progesterone did not change. These results in association with previous reports indicate that the zona reticularis of the guinea pig adrenal cortex (in contrast to the zona fasciculata) is not regulated by ACTH in terms of either steroidogenesis or maintenance of cell growth.

Adrenal Cortex↗
PubMed1983

Purification of a pregnenolone-binding protein in the soluble fraction of the guinea-pig adrenal cortex: differentiation from pregnenolone sulfotransferase.

A pregnenolone-binding protein has been purified from the 235,000 g soluble fraction of the guinea-pig adrenal cortex. The binding protein had an apparent molecular weight of 34,000 when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Since the functional status of the pregnenolone-binding protein is not known, a search for intrinsic catalytic activity was made. Because the binding protein is known to be a soluble protein consideration of a soluble enzyme activity was made which led to an investigation of the enzyme 3B-steroid sulfotransferase. Pregnenolone sulfotransferase activity, however, which was present in the soluble fraction, was found to be distinguishable from the pregnenolone-binding protein. Although the physicochemical distinction between these two factors was consistently noted with numerous experiments, it is speculated that there may exist a specific functional interaction between them. It was particularly interesting that both factors were concentrated in the inner cortical zone.

Adrenal Cortex↗
PubMed1983

Unconjugated and sulfoconjugated steroids in plasma and zones of the adrenal cortex of the guinea pig.

The following steroids were measured in their unconjugated and sulfoconjugated forms in plasma and in the outer and inner zones of the adrenal cortex of the guinea pig: pregnenolone, 17-hydroxypregnenolone, 21-hydroxypregnenolone, dehydroepiandrosterone and deoxycorticosterone. In plasma, pregnenolone and 21-hydroxypregnenolone were the predominant unconjugated steroids with concentrations 10-30 times higher than the other three steroids. Among the sulfoconjugated steroids, pregnenolone sulfate had a concentration 25-50 times higher than the other sulfoconjugates. For each steroid except 21-hydroxypregnenolone the sulfoconjugated form was present in a concentration 2-7 times higher than the unconjugated form. In the adrenal cortex, the content of 21-hydroxypregnenolone was significantly higher in the outer zone than in the inner zone and was present in amounts 3-100 times greater than the other unconjugated steroids in the outer zone. On the other hand, the content of pregnenolone was significantly greater in the inner zone than the outer zone, and was present in amounts 3-80 times greater than the other unconjugated steroids in the inner zone. With the exception of 21-hydroxypregnenolone and deoxycorticosterone, the steroid sulfoconjugates were significantly higher in the inner cortical zone. As in plasma, pregnenolone sulfate was the most abundant sulfoconjugated steroid. This report also describes preliminary studies concerning sulfurylated hydroxyl groups in different positions of 21-hydroxypregnenolone. The sulfoconjugate was prepared by using partially purified steroid sulfotransferase from the guinea pig adrenal. The results obtained indicated that of the total 21-hydroxypregnenolone conjugate formed, approximately 40% was the 21-sulfate and 20% the 3-sulfate, whereas 40% was non-hydrolyzable with the techniques used and was not further characterized.

Adrenal Cortex↗
PubMed1982

Refractory Cushing's disease caused by multinodular ACTH-cell hyperplasia.

A patient with pituitary-dependent hypercortisolism, unresponsive to resection of nodules in the anterior lobe, is described. Histochemical stains of the nodules showed multiple, focal, cellular expansions of the fibrovascular stroma. Transitions between normal and expanded adenohypophysial acini were present. Immunoperoxidase stains for ACTH and other pituitary hormones revealed that these multiple foci contained an excess of ACTH-positive cells. Less than 10% of the cells in these foci were negative for ACTH and positive for other hormones. Serial sections showed that these foci of predominantly ACTH-producing acini were not connected. Clinical, morphological, and immunohistochemical data indicated that ACTH-cell hyperplasia caused Crushing's disease in this patient. Pathologic study of individual cases should concentrate on determining whether hyperplasia or adenoma exist at the time of surgical exploration of the pituitary gland, since this determination is important to proper treatment. Tentative criteria to recognize ACTH-cell hyperplasia are: 1. Multiple foci of ACTH laden cells. 2. A minor subpopulation of cells of alternate hormone series. 3. Expansion without destruction of acini in the adenohypophysis.

Adenoma↗
PubMed1982

Localization of functional adrenal tumors by computed tomography and venous sampling.

Fifty-eight patients with functional lesions of the adrenal gland underwent radiographic evaluation. Twenty-eight patients had primary aldosteronism (Conn syndrome), 20 had Cushing syndrome, and 10 had pheochromocytoma. Computed tomography (CT) correctly identified adrenal tumors in 11 (61%) of 18 patients with aldosteronomas, 6 of 6 patients with benign cortisol-producing adrenal tumors, and 5 (83%) of 6 patients with pheochromocytomas. No false-positive diagnoses were encountered among patients with adrenal adenomas. Bilateral adrenal hyperplasia appeared on CT scans as normal or prominent adrenal glands with a normal configuration; however, CT was not able to exclude the presence of small adenomas. Adrenal venous sampling was correct in each case, and reliably distinguished adrenal tumors from hyperplasia. Recurrent pheochromocytomas were the most difficult to localize on CT due to the surgical changes in the region of the adrenals and the frequent extra-adrenal locations.

Adenoma↗
PubMed1982

Regulation of the pituitary-adrenal axis and corticosteroid-binding globulin-cortisol interaction in the guinea pig.

Adult male guinea pigs were used to examine pituitary-adrenal function and corticosteroid-binding globulin (CBG)-cortisol interaction. A biphasic pattern in the circadian rhythm of plasma cortisol was observed, with nadirs occurring at 0800 and 2400 h and peaks and 1600 and 0400 h. An excellent correlation was noted between total and free plasma cortisol levels. In contrast, no correlation was noted between CBG binding capacity and either the total or free plasma cortisol level. The free plasma cortisol concentration ranged from 0.6-5.8 micrograms/dl, representing 6.1-14.5% of the total cortisol concentration. The CBG binding capacity ranged from 12.2-161.7 micrograms/dl, and the binding affinity was 1.3-2.2 x 10(7) M-1 at 22 C, which is 20-fold lower than that of human CBG. These results suggest that CBG in the guinea pig has a relatively minor effect on the plasma distribution of cortisol, and that free plasma cortisol is dependent on cortisol binding to nonspecific plasma proteins as well as on the total plasma cortisol concentration. It was found that the guinea pig was relatively resistant to dexamethasone suppression, requiring at least 1 mg/kg BW to obtain essentially complete suppression of the pituitary-adrenal axis. In addition, it was found that administering dexamethasone 6 h before the time that the animals were killed led to suppression, whereas giving the steroid 12 h before killing the animals was totally ineffective. Stress induced by both ether vapor and histamine injection significantly increased plasma cortisol levels. When the guinea pigs were treated with a 1 mg/kg BW dose of dexamethasone 6 h before the stimulus, however, a marked suppression of the plasma cortisol increment secondary to application of the stressful stimulus occurred.

Animals↗
PubMed1981

Functional differences between the outer and inner zones of the guinea pig adrenal cortex.

The guinea pig adrenal cortex is grossly composed of two regions: an outer, yellow zone and an inner, brown zone. These zones, which represent 33% and 66% of the total adrenocortical volume, respectively, can be separated by blunt dissection. It has been previously reported that specific pregnenolone and pregnenolone sulfate binding proteins are present in the high speed supernatant fraction (cytosol) prepared from the whole adrenal cortex of the guinea pig. However, when cytosol was prepared from the separate outer and inner cortical zones, it was found that the steroid-binding proteins were concentrated in the inner zone. This correlated with the level of pregnenolone which was significantly greater in the cytosol of the inner zone where greater than 50% was found to be bound. In contrast, the concentration of cortisol was 30 times greater in the cytosol of the outer cortical zone and less than 4% was found to be bound. These data suggest that cortisol is produced primarily in the outer cortical zone, a region which comprises only one-third of the total cortical volume. On the other hand, the coexistence of pregnenolone and its binding protein in the inner cortical zone, a region which comprises two-thirds or the greatest cortical volume, indicates a different functional status for this zone. The exact hormonal control of these two vastly different regions (chromatically, morphologically, and functionally) remains to be determined. It is speculated that the inner cortical zone of the adult guinea pig adrenal is the counterpart of the fetal cortex which did not involute.

Adrenal Cortex↗
PubMed1979

Purification of bovine adrenocortical and brain tubulin. A comparative study.

Microtubules from the cow adrenal cortex and brain were purified by three cycles of the temperature-dependent polymerization-depolymerization procedure. Whereas tubulin comprised approximately 8--10% of soluble brain protein, it comprised only 0.5-1.0% of the soluble adrenocortical protein. The partially purified tubulin from both sources gave similar results in the following studies: (1) [3H]colchicine binding examined by Scatchard analysis revealed an apparent Ka of 1 . 10(6) M-1 and a colchicine/tubulin molar binding ratio of 0.4-0.6; (2) tyrosylation studies using a specific tubulin-tyrosine ligase (which adds a tyrosine residue to the C-terminal glutamate or glutamine of the alpha-chain) in conjunction with carboxypeptidase A (which recovers the tyrosine) and (3) amino acid analysis. Examination of protein bands, in addition to the tubulin doublet of 55 000 molecular weight, on sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a difference between the two tubulin preparations. The adrenocortical preparation had protein bands corresponding to apparent molecular weight of 36 000, 60 000, and 68 000. In contrast the brain preparation had only proteins of molecular weights greater than 200 000 (these bands were absent in all adrenal preparations). It would thus appear that if proteins which copurify with tubulin through repeated cycles of polymerization-depolymerization play a role in either microtubule formation or function there is a distinct difference between neural and non-neural tissue.

Adrenal Cortex↗
PubMed1979

Computed tomography in adrenal tumors.

Computed tomography (CT) was used to evaluate 26 patients with a variety of adrenal lesions. Surgical proof was available in 22 patients and clinical confirmation with a variety of other studies in the other four patients. Nine patients ahd aldosterone-producing adrenal adenomas and CT correctly identified seven. Four patients had cortisol-producing adenomas and five patients had cortisol-producing carcinomas; CT identified each of these tumors. Prominent but normal shaped glands were seen in each of the four patients with adrenal hyperplasia. Adrenal metastases from malignant melanoma in two patients were identified. Only one of two pheochromocytomas in two patients could be seen on CT. CT is a noninvasive method of localizing adrenal tumors and may be helpful in distinguishing adenomas from adrenal hyperplasia.

Adenoma↗
PubMed1978

Adrenal cortical tumors with low attenuation coefficients: a pitfall in computed tomography diagnosis.

Four cases of adrenal tumors with unusually low attenuation coefficients are reported. The tumors presented with values ranging from 8 to 17 EMI units (EU: 500 scale) instead of the expected 30 to 40 EU range of the remainder of our adrenal tumors. Two of these patients had primary aldosteronism and two had Cushing's syndrome. An unusually high lipid content may be responsible for the lucent appearance.

Adrenal Cortex Neoplasms↗