Evidence of in Vivo Inhibition of 11<i>β</i>-Hydroxylation of Steroids by Dehydroepiandrosterone in the Dog<sup>1</sup>

Fragachán, F.; Nowaczynski, W.; Bertranau, E.; Kalina, Maria; Genest, Jacques; Robinson, Pauline; Mion, C

doi:10.1210/endo-84-1-98

Cited by 18 publications

(3 citation statements)

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“…In heminephrectomized female rats treated with testosterone, Colby et al 14 induced hypertension associated with elevated plasma levels of DOC. Fragachan et al 15 perfused dog adrenals in vivo with DHEA and competitively inhibited 11-hydroxylation of DOC to corticosterone and S to Cortisol. Female rats were rendered hypertensive after chronic treatment with methylandrostenediol by McCall et al 16 .…”

Section: Journal Of Pediatric Endocrinology and Metabolismmentioning

confidence: 99%

Hypertension and Virilization Caused by a Unique Desoxycorticosterone- and Androgen-Secreting Adrenal Adenoma

Soranno¹,

Prasad²,

David³

et al. 1999

Journal of Pediatric Endocrinology and Metabolism

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We describe a rare androgen and desoxycorticosterone (DOC)-secreting adrenal tumor in a non-Cushingoid 14 year-old Haitian girl with secondary amenorrhea, hypertension and virilization. Her steroid pattern simulated an 11 beta-hydroxylation defect with notable elevation of adrenal androgens, 11-desoxycortisol (S), DOC, 17 alpha-hydroxyprogesterone and pregnenelone. Exogenous ACTH stimulated steroidogenesis. A CAT scan unfortunately failed to delineate an adrenal mass. Dexamethasone (DEX) was administered, therefore, which partially suppressed androgen levels, reduced DOC and S by 80% and 82% respectively, and normalized blood pressure. Nevertheless, the response to glucocorticoid was incomplete and an MRI was obtained, which revealed a right adrenal tumor. Post surgery, the patient promptly resumed menses and became normotensive. This case illustrates that ACTH and DEX cannot reliably differentiate tumor from hyperplasia, whereas the simultaneous increase of delta 4 and delta 5 steroids, present here, may favor a tumor. This case also allows speculation that the hypersecretion of DOC may result from inhibition of 11 beta-hydroxylase activity by excess androgens. The importance of appropriate imaging for diagnosis is underscored.

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Section: Journal Of Pediatric Endocrinology and Metabolismmentioning

confidence: 99%

Hypertension and Virilization Caused by a Unique Desoxycorticosterone- and Androgen-Secreting Adrenal Adenoma

Soranno¹,

Prasad²,

David³

et al. 1999

Journal of Pediatric Endocrinology and Metabolism

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“…Plasma cortisol concentration has been widely used as an index of pituitary function (Landon, James & Stoker, 1965;Landon, Wynn & James, 1963;Greenwood, Landon & Stamp, 1966) and while it is obviously less satisfactory than direct measurement of plasma ACTH concentration, in most cases it provides an acceptable indirect guide. However, it has recently been shown by Fragachan, Nowaczynski, Bertranav, Kalina & Genest (1969) that dehydroepiandrosterone (DHA) inhibits 1 la-hydroxylation in vivo in the dog, and since plasma levels of DHA have been shown to increase markedly during the first 7 days of fasting in obese subjects (Hendrikx, Heyns & de Moor, 1968) it is possible that in these circumstances plasma cortisol is not a true index of ACTH secretion. In fact ACTH levels might be very high in a vain attempt to stimulate increased cortisol secretion during the stressful situation of total fasting.…”

Section: The Dissociation Between Renin and Aldosteronementioning

confidence: 99%

The Natriuresis of Fasting: Relationship to Changes in Plasma Renin and Plasma Aldosterone Concentrations

et al. 1970

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1. The relationship of changes in plasma renin and plasma aldosterone concentration to electrolyte balance was studied during total fasting and during sodium deprivation followed by total fasting.2. During simple sodium deprivation obese subjects lost significantly more sodium than lean subjects, but the rise in plasma renin concentration (PRC) was similar in the two groups.3. During total fasting there was a failure of PRC to increase in the expected manner despite a marked negative sodium balance. In the early stages of the fast, PRC decreased in nine of eleven subjects while subsequently it increased in all subjects. 4. During sodium deprivation PRC and plasma aldosterone concentration (PAC) rose in all subjects studied, but in the first few days of a period of total fasting immediately following, there was a fall in PRC in eight of ten subjects studied, while PAC continued to rise in five of six subjects in whom it was measured.5. These results are discussed in relation to the concept of the renin-angiotensin system as a regulator of aldosterone secretion.

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“…Partial deficiency of both enzymes can best be explained by the proposition that one defect is congenital and the other acquired as a result of the inhibitory effect of increased androgens on 1 18hydroxylation in patients with congenital 21-hydroxylase deficiency, or on 3p-hydroxy;A5-steroid dehydrogenase in patients with 1 1 B-hydroxylase deficiency. This phenomenon has been well documented in animals, both in vifro [26] and in vivo [27,28,29]. The levels of androgens critical for enzyme inhibition would be determined by the intra-adrenal concentrations achieved [30] as a result of the primary defect [2].…”

Section: Discussionmentioning

confidence: 98%

Late‐onset congenital adrenal hyperplasia in women with hirsutism

Arnaout

1992

Eur J Clin Investigation

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Hirsutism in women is a clinical manifestation of excessive production of androgens. The source of the excess androgen may be either the ovaries or the adrenal glands, or increased peripheral conversion of weak androgenic hormones to more potent androgens. Late-onset (non-classic) congenital adrenal hyperplasia is a cause of hirsutism in adult women, but its frequency and the patterns of abnormalities in adrenal hormone secretion are not well understood. The frequency of non-classical adrenal hyperplasia due to deficiencies of 3 beta-hydroxy-delta 5-steroid dehydrogenase, 21-hydroxylase, and 11 beta-hydroxylase among 65 women with hirsutism were determined. All enzyme defects were identified by comparing the patients' hormonal responses to 0.25 mg intravenous bolus of alpha 1-24-ACTH with those of age-matched normal women. The hormones measured in plasma during the ACTH stimulation tests were progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, DHEA-sulfate, androstenedione, testosterone, 11-deoxycortisol, and cortisol. Similarly these hormones were measured after overnight 1 mg oral dexamethasone. Twelve women (18.5%) had 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency, 24 (37%) 21-hydroxylase deficiency, and 14 (21.5%) 11 beta-hydroxylase deficiency. Women with 21-hydroxylase deficiency also had evidence of a partial deficiency in 11 beta-hydroxylase activity (12 of the 24 patients). Similarly, most (11 of the 14) of the women with 11 beta-hydroxylase deficiency also had evidence of a deficiency in 3 beta-hydroxy-delta 5-steroid dehydrogenase activity. Among the 15 patients with no adrenal biosynthetic defect, eight had high plasma androgen concentrations, and seven had normal concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

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Evidence of in Vivo Inhibition of 11β-Hydroxylation of Steroids by Dehydroepiandrosterone in the Dog¹

Cited by 18 publications

References 0 publications

Hypertension and Virilization Caused by a Unique Desoxycorticosterone- and Androgen-Secreting Adrenal Adenoma

Hypertension and Virilization Caused by a Unique Desoxycorticosterone- and Androgen-Secreting Adrenal Adenoma

The Natriuresis of Fasting: Relationship to Changes in Plasma Renin and Plasma Aldosterone Concentrations

Late‐onset congenital adrenal hyperplasia in women with hirsutism

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Evidence of in Vivo Inhibition of 11β-Hydroxylation of Steroids by Dehydroepiandrosterone in the Dog1

Cited by 18 publications

References 0 publications

Hypertension and Virilization Caused by a Unique Desoxycorticosterone- and Androgen-Secreting Adrenal Adenoma

Hypertension and Virilization Caused by a Unique Desoxycorticosterone- and Androgen-Secreting Adrenal Adenoma

The Natriuresis of Fasting: Relationship to Changes in Plasma Renin and Plasma Aldosterone Concentrations

Late‐onset congenital adrenal hyperplasia in women with hirsutism

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Evidence of in Vivo Inhibition of 11β-Hydroxylation of Steroids by Dehydroepiandrosterone in the Dog¹