The Metabolism of [4-14c]-Progesterone by Adrenocortical Tissue From Patients With Cushing's Syndrome

Ward, Pamela J.; Grant, J. K.

doi:10.1677/joe.0.0260139

Cited by 39 publications

(17 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Earlier studies in which direct comparisons were made between hyperplastic and adenomatous adrenal tissue showed little or no difference between steroid secretion patterns (24)(25)(26). Only D'Agata et al (27), studying the in vitro activities of several adrenocortical enzymes (not including 11/3-hydroxylase) in six adrenal adenomas, found increased 21-hydroxylase activity in adrenal adenomas compared with that in normal adrenal tissue.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Adrenal Autonomy in Cushing's Syndrome: A Comparison betweenin Vivoandin VitroResponsiveness of the Adrenal Gland

Lamberts¹,

Zuiderwijk²,

Uitterlinden³

et al. 1990

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

We measured cortisol and precursor steroid production in response to ACTH, cholera toxin, and forskolin by the dispersed adrenocortical cells prepared from the adrenal glands of 10 patients with different forms of Cushing's syndrome. The cells prepared from the hyperplastic adrenal glands from 4 patients with Cushing's disease responded in a dose-dependent manner to ACTH, cholera toxin, and forskolin. The adrenal cells prepared from 4 encapsulated adrenal adenomas showed no (n = 2), a lowered (n = 1), or a clear (n = 1) response of cortisol release to ACTH. The cells prepared from the adrenal glands of 1 patient with dysplastic micronodular adrenal glands showed a limited response to ACTH, while the cells from an adrenocortical carcinoma, which secreted very little cortisol per cell, were unresponsive to ACTH, cholera toxin, and forskolin. The reaction of the dispersed adrenal cells from these 10 patients to ACTH, cholera toxin, and forskolin showed a close correlation (P less than 0.001 in all instances). This suggests that the defect in autonomous glands is not located at the level of the ACTH receptor, but, rather, involves the adenylate cyclase complex as a whole or its coupling to cAMP-dependent protein kinase. The release into the medium of the cortisol precursors deoxycortisol, 17-hydroxyprogesterone, and progesterone showed that the four autonomous nodules were characterized by a significantly higher deoxycortisol/cortisol ratio in the medium (P less than 0.01), suggesting a relative blockade of 11 beta-hydroxylase in these adrenal adenomas. This was further substantiated in cells from several adrenals by a significant increase in the release of these precursors in response to ACTH in the absence of a cortisol response. We conclude the following. 1) Adrenal adenoma formation in patients with Cushing's syndrome is accompanied by a parallel decrease in the stimulation of the release of steroid hormones in response to ACTH, cholera toxin, and forskolin. This points to a defect in the adenoma cells beyond the ACTH receptor. 2) Adrenal adenoma formation in patients with Cushing's syndrome is accompanied by a relative blockade of 11 beta-hydroxylase activity. 3) By comparing the preoperative dynamic tests of the pituitary-adrenal axis, the plasma ACTH concentration, the morphology of the adrenal glands, and their in vitro responsiveness, a gradual transition from pituitary to (partial) adrenal autonomy could be recognized in several patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of Adrenal Autonomy in Cushing's Syndrome: A Comparison betweenin Vivoandin VitroResponsiveness of the Adrenal Gland

Lamberts¹,

Zuiderwijk²,

Uitterlinden³

et al. 1990

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

show abstract

“…Although Race & Wu (1961) using whale tissue found that 17-oxosteroid concentrations in the zona reticularis were higher than those in other parts of the gland, and Ofstad, Lamvik, St0a & Emberland (1961) gave evidence for similar functional zonation in man, the work of Griffiths, Grant & Symington (1963) and Ward & Grant (1963) suggested that in man both the zona fasciculata and the z. reticularis can form testosterone and cortisol, and hence that these zones should be considered as a single functional unit. This view has been slightly modified by Jones & Griffiths (1968) who found that in guinea-pigs, sulphurylation of dehydroepiandrosterone may occur predominantly in the z. reticularis.…”

Section: Introductionmentioning

confidence: 99%

“…In man, dehydroepiandrosterone is a prominent secretory product, especially as the sulphate (Baulieu, 1965) while in incubation studies, testosterone has also been identified (Kase & Kowal, 1962;Ward & Grant, 1963). Other C19 steroids commonly found in adrenal studies of various species are androstenedione and 1 l/?-hydroxyandrostenedione (for review see Vinson & Whitehouse, 1970a).…”

Section: Introductionmentioning

confidence: 99%

Functional Zonation of Adrenocortical Tissue in the Brush Possum (Trichosurus Vulpecula)

Vinson¹,

PHILLIPSt²,

Jones³

et al. 1971

Journal of Endocrinology

View full text Add to dashboard Cite

The relationship of structure and function in the adrenal gland of the possum Trichosurus vulpecula, has been studied using in-vitro incubation techniques. It was shown that both 17\g=a\-hydroxycorticosteroids and 17-deoxycorticosteroids were produced from radioactive pregnenolone and progesterone, and that these transformations occurred both in the definitive cortex as well as in a special zone of hypertrophied tissue found only in the adult female.In support of earlier findings, it was also shown that the adrenal cortex of the possum has a remarkable capacity to produce C19 steroids (including androstenedione and testosterone) from the radioactive precursors. While most of the transformations occurred with equal efficiency in both types of tissue, the reduction of androstenedione to testosterone seemed to take place more readily in the special hypertrophied zone of the adult female.In studies in vivo, it was found that levels of testosterone in the peripheral blood of the adult female possum were extremely high compared with man. Variations in testosterone levels were not apparently correlated with the stage of the oestrous cycle. The possible pathways by which the adrenal products are synthesized, and their physiological implications are discussed.

show abstract

“…The main difference was the presence of an active 16a-hydroxysteroid dehydrogenase. The reason for the increase in activity of this enzyme is obscure but 16a-hydroxy compounds are important in oestrogen metabolism (Breuer & Nooke, 1959;Levitz, Rosen & Twombly, 1960), as metabolites of progesterone (Villee, Dimoline, Engel, Villee & Racker, 1962;Ward & Grant, 1963) and in connexion with the postulated salt-losing hormone (Neher, Desaulles, Vischer, Wieland & Wettstein, 1958;Cope & Parry, 1959). Any or none of these possibilities may apply, but histological techniques do not allow us to discriminate between them.…”

Section: Discussionmentioning

confidence: 99%

Hydroxysteroid Dehydrogenases in the Human Adrenal Cortex

Calman¹,

Baillie²,

Ferguson³

et al. 1966

Journal of Endocrinology

View full text Add to dashboard Cite

The histochemical utilization of 3\g=a\-,3\g=b\-,6\g=b\-,11\g=a\-,11\g=b\-,12\g=a\-,16\g=a\-,16\g=b\-, 17\g=a\-,17\g=b\-,20\g=a\-, 21-and 24-hydroxysteroids by three normal adult human adrenal glands, two human foetal adrenal glands, three adrenals from patients with Cushing's syndrome and one adrenal adenoma are described.The normal adult human adrenal showed high 16\g=b\-hydroxysteroid dehydrogenase activity in the zona glomerulosa. Activity restricted to the outer part of the zona fasciculata was recorded with 3\g=a\-,3\g=b\-,6\g=b\-, 11\g=b\-, 16\g=a\-,16\g=b\-, and 17\g=b\-hydroxysteroids. The zona reticularis utilized 3\g=a\-,3\g=b\-, 11\g=b\-,16\g=b\-and 17\g=b\-hydroxysteroids less well than the zona fasciculata.The adrenals of Cushing's syndrome showed activity only for 3\g=b\-and 16\g=b\-hydroxysteroiddehydrogenases; this activity was noted in all three zones. The activity pattern of the adrenal adenoma resembled that of the normal adult human adrenal except that greater activity for 16\g=a\-hydroxysteroid dehydrogenase was noted.The foetal part of the human foetal cortex was extremely active, showing 3\g=a\-,3\g=b\-,6\g=b\-,11\g=b\-,12\g=a\-,16\g=a\-,16\g=b\-,17\g=b\-,20\g=b\-and 21-hydroxysteroid dehydrogenase activity. The definitive cortex behaved similarly to the adult gland and possessed 3\g=a\-,3\g=b\-,11\g=b\-,16\g=b\-and 17\g=b\-hydroxysteroid dehydrogenases; some evidence of zoning of the definitive cortex was seen with the 16\g=b\-hydroxysteroid.The relevance of these findings in the light of current knowledge of adrenal zonation is discussed.

show abstract

The Metabolism of [4-14c]-Progesterone by Adrenocortical Tissue From Patients With Cushing's Syndrome

Cited by 39 publications

References 16 publications

Characterization of Adrenal Autonomy in Cushing's Syndrome: A Comparison betweenin Vivoandin VitroResponsiveness of the Adrenal Gland

Characterization of Adrenal Autonomy in Cushing's Syndrome: A Comparison betweenin Vivoandin VitroResponsiveness of the Adrenal Gland

Functional Zonation of Adrenocortical Tissue in the Brush Possum (Trichosurus Vulpecula)

Hydroxysteroid Dehydrogenases in the Human Adrenal Cortex

Contact Info

Product

Resources

About