The Adrenal Androgen-Stimulating Hormone Does Not Exist

Anderson, D. C.

doi:10.1016/s0140-6736(80)91889-9

Cited by 99 publications

(47 citation statements)

References 13 publications

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“…It is conceivable that this putative adrenal androgenstimulating hormone is suppressed more readily than ACTH by exogenous cortisol in patients treated for CAH, resulting in a far greater decrease in serum levels of DHEAS than of 17-OHP. The existence of such a hormone, however, has been challenged and alternative explanations have been suggested (2,22).…”

Section: Resultsmentioning

confidence: 99%

“…(1) normal linear growth; (2) normal bone age and normal rate of advancement of bone age; (3) no evidence of ongoing inappropriate virilization such as premature appearance of pubic hair or phallic or clitoral enlargement; (4) urinary 17 ketosteroids at or below age-related upper limits (14); (5) serum concentration of 17-hydroxyprogesterone (17-OHP) below 500 ng/dl (one patient with a serum level of 17-OHP of 757 ng/ dl was considered adequately controlled because the rest of the criteria were fulfilled); and (6) normal testicular size for age or regular menses in adolescent male and female subjects, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Disproportionate Supression of Dehydroepiandrosterone Sulfate (DHEAS) in Treated Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

et al. 1983

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SummarySerum concentrations of dehydroepiandrosterone sulfate (DHEAS) were measured in 28 patients (18 females, 10 males) with congenital adrenal hyperplasia due to 21-hydroxylase deficiency who were treated with oral hydrocortisone (non-salt losers) or hydrocortisone and 9-a-fluorohydrocortisone (salt-losers). Adequacy of therapy was assessed by clinical findings, determination of bone age, urinary excretion of 17-ketosteroids, and serum concentration of 17-hydroxyprogesterone. These allowed the separation of patients into three groups: poorly controlled, adequately controlled and overtreated. Individual values for serum levels of DHEAS were compared to mean normal values for age. In the adequately controlled and overtreated patients, mean serum concentrations of DHEAS were significantly lower than normal values for age ( P < 0.05). In the poorly treated patients, the mean serum concentration of DHEAS was not significantly different from normal values for age ( P = 0.50).These data indicate that the serum concentration of DHEAS is overly suppressed in treated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. This finding suggests that measurement of the serum levels of DHEAS has limited value in assessing the adequacy of therapy in this disease. Abbreviations CAH, congenital adrenal hyperplasia due to 21-hydroxylase deficiency DHEAS, dehydroepiandrosterone sulfate 17-OHP, 17-hydroxyprogesterone SDS, standard deviation score A major goal in long term management of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is to suppress the effects of excessive adrenal androgens. The adequacy of suppression has been traditionally monitored by periodic measurement of 24-h urinary excretion of 17-ketosteroids and pregnanetriol. The reliability of these assays, however, is hampered by inaccuracies in collection of 24-h urine specimens. A suitable compound that can be measured in blood, therefore, has been searched for by several investigators. Dehydroepiandrosterone sulfate (DHEAS), the most abundant adrenal androgen, seems to be a likely candidate for this purpose because it is almost exclusively synthesized by the adrenal glands (17,19). Moreover, as DHEAS has a long half-life (24, 26), its concentration in serum is less susceptible to diurnal variations (25).Recent studies have demonstrated that serum levels of DHEAS are increased in patients with untreated CAH (1 1, 15,23); however, data on the serum concentration of the hormone during therapy are very limited. Serum levels of DHEAS did not increase in six patients with CAH when therapy was discontinued for 3 days (33). Golden et al. (1 1) found elevated levels of serum DHEAS in patients with CAH only when they were overtly undertreated, but values for serum levels of DHEAS were not correlated with the age of the patients. Because secretion of DHEAS is age dependent (8,15,23), its role in the management of patients with CAH cannot be quantitated unless appropriate age-matched control values are applied. The ...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Disproportionate Supression of Dehydroepiandrosterone Sulfate (DHEAS) in Treated Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

et al. 1983

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“…The second group comprises hypotheses that suggest that specific hormone(s) act on some form of precursor cell type (either stem cells or differentiated zona fasciculata cells) to cause the development of the zona reticularis. The concept of an adrenal androgenstimulating hormone was popular during some periods of the past (Anderson 1980, Parker & Odell 1980, but over the subsequent decades, no such hormone was ever defined. Premature adrenarche is occasionally caused by a pituitary tumor (Iwatani et al 1992), but the secreted tumor products have not been shown to involve a specific adrenarche-stimulating hormone.…”

Section: Hypotheses Concerning the Establishment And Maintenance Of Zmentioning

confidence: 99%

Adrenarche: a cell biological perspective

Hornsby¹

2012

Journal of Endocrinology

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Adrenarche is a cell biological and endocrinological puzzle. The differentiation of the zona reticularis in childhood in humans requires special techniques for study because it is confined to humans and possibly a small number of other primates. Despite the rapid progress in the definition of adrenocortical stem/progenitor cells in the mouse, the factors that cause the differentiation of adrenocortical cells into zonal cell types have not been identified. There are, however, many candidates in the Wnt, Hedgehog, and other families of signaling molecules. A suitable system for identifying authentic stem cells, capable of differentiation into all zones, has yet to be developed. It is proposed here that the in vitro differentiation of pluripotent cells, combined with appropriate in vitro and in vivo methods for validating authentic adrenocortical stem cells, is a promising approach to solving these questions.

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“…possible mechanism is that of long-term exposure of the zona reticularis to cortisol as a consequence of blood flow through the adrenal from the outer cortex to the inner, which may bring about an alteration in the enzymes involved in adrenal androgen production (23). It has also been suggested that maturational changes in the activities of some adrenal enzymes (17-hydroxylase, 17-20-lyase and the 3b-hydroxysteroid dehydrogenase, D 4-5 isomerase system) may account for alterations in steroidogenesis favouring androgens (13)(14)(15).…”

Section: Figurementioning

confidence: 99%

“…Alternatively, factors outside the adrenal gland have been proposed, such as prolactin (16), growth hormone (17), insulin (18), sex steroids (19,20) and fragments of the ACTH precursor molecule, pro-opiomelanocortin, such as b-endorphin (21) and joining peptide (21,22). The existence of such a cortical androgen stimulating hormone has been disputed (23)(24)(25). The present study was designed to examine the influence of ageing and sex on the relative production of cortisol, androstenedione and dehydroepiandrosterone (DHEA), basally and in response to ACTH, and thus enable us to examine the influence of possible endogenous maturational changes that may influence differential production of cortisol and androgens.…”

Section: Introductionmentioning

confidence: 99%

Intra-adrenal factors are not involved in the differential control of cortisol and adrenal androgens in human adrenals

Fearon

Clarke²,

McKenna³

et al. 1998

European Journal of Endocrinology

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The differential control of adrenal androgens and cortisol may be due to intra-adrenal factors, which may be age-or sex-related, or due to extra-adrenal factors, such as circulating hormones. The purpose of this study was to identify any intrinsic differences that may exist in steroidogenic production occurring within adrenals obtained from males and females, and any maturational differences that may evolve with age. Using human adrenals from 48 transplant donors (32 males, 16 females; ages 5-60 years), the influences of age and sex on basal production of and ACTH-stimulated cortisol, androstenedione and dehydroepiandrosterone (DHEA) were examined in freshly prepared adrenal cell suspensions. Basal and ACTH-stimulated cortisol, androstenedione and DHEA production were similar in adrenals from males and females and did not correlate significantly with age when the whole group was examined. When steroidogenesis in male and female adrenals was examined separately against age, a significant correlation was observed only for basal and ACTH-stimulated androstenedione in adrenals from males in the younger age group, 5-30 years (basal: r ¼ 0.84, P ¼ 0.0001; ACTH-stimulated: r ¼ 0.52, P ¼ 0.007). Examination of the relationships between the steroids disclosed that the basal and ACTH-stimulated cortisol/androgen ratios did not correlate significantly with age, but the androstenedione/DHEA ratio showed a significant direct relationship with age in males only (basal: r ¼ 0.53, P ¼ 0.006; ACTH-stimulated: r ¼ 0.5, P=0.01).These data suggest that the influences of sex and age are minor in the modulation of adrenal steroidogenesis and support the concept that extra-adrenal factors dominate in the differential modulation of adrenal androgens and cortisol. The relationship between the androstenedione/ DHEA ratio and increasing age in men is consistent with the recently reported stimulatory effect of testosterone on adrenal steroidogenesis by induction of the conversion of DHEA to androstenedione.

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The Adrenal Androgen-Stimulating Hormone Does Not Exist

Cited by 99 publications

References 13 publications

Disproportionate Supression of Dehydroepiandrosterone Sulfate (DHEAS) in Treated Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Disproportionate Supression of Dehydroepiandrosterone Sulfate (DHEAS) in Treated Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Adrenarche: a cell biological perspective

Intra-adrenal factors are not involved in the differential control of cortisol and adrenal androgens in human adrenals

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