2 A critical review of the origin and control of adrenal androgens

McKenna, T. J.; Fearon, Ursula; Clarke, D.; Cunningham, S. K.

doi:10.1016/s0950-3552(97)80035-1

Cited by 47 publications

(25 citation statements)

References 75 publications

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“…Much of a woman's circulating androgens arise directly or indirectly from adrenal androgens, and these, like cortisol, respond to stress-induced secretions of ACTH (Parker 1991;McKenna et al 1997). Androgens in women have been shown to rise in response to a variety of stressors, including surgery (Batrinos et al 1999), cognitive tasks (Boudarene et al 2002), and endurance exercise such as running and cycling (Webb et al 1984;Keizeret al 1987;Copeland et al 2002).…”

Section: Adrenal Androgens: Environmental Influencesmentioning

confidence: 99%

Waist‐to‐Hip Ratio across Cultures: Trade‐Offs between Androgen‐ and Estrogen‐Dependent Traits

Cashdan¹

2008

Current Anthropology

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Section: Adrenal Androgens: Environmental Influencesmentioning

confidence: 99%

Waist‐to‐Hip Ratio across Cultures: Trade‐Offs between Androgen‐ and Estrogen‐Dependent Traits

Cashdan¹

2008

Current Anthropology

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“…The increase in steroidogenesis after ACTH stimulation is fueled by the use of cholesterol stored in liposomes within the adrenocortical cells, by uptake of cholesterol from the circulation, and by de novo synthesis of cholesterol (14). Although ACTH stimulates adrenal androgen production, it is well known that ACTH alone is unable to maintain a normal cortisol to androgen ratio (87). In fact, there are many physiological and pathological conditions in which there is a dissociation of adrenal androgen and cortisol production.…”

Section: Does the Extrapituitary-adrenocortical Stress Response Constmentioning

confidence: 99%

Adrenocorticotropin (ACTH)- and Non-ACTH-Mediated Regulation of the Adrenal Cortex: Neural and Immune Inputs

Bornstein

Chrousos

1999

The Journal of Clinical Endocrinology & Metabolism

276

121

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The maintenance of life depends on the capacity of the body to sustain its steady state or homeostasis; hence, the survival of the organism relies on its ability to react and adapt to the constant bombardment by physical and emotional threats or stressors (1, 2). To accomplish this, all living beings have developed an efficient but complex adaptive response system that allows the integration of the necessary defense mechanisms directed against both external and internal stressors. This coordinated response, the stress response, involves the nervous, endocrine, and immune systems. A qualitatively and quantitatively appropriate and time-limited stress response is a prerequisite for a healthy life. Inappropriate or inappropriately excessive and chronic hyperactivation of the stress system may lead to disease and, eventually, premature death.The two major peripheral limbs of the stress system are the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (1, 2). Their central components are, respectively, located in the hypothalamus and the brain stem. Stress-induced activation of the HPA axis is associated with release of hypothalamic CRH and vasopressin (AVP), the principal regulators of anterior pituitary corticotropin (ACTH) secretion, into the hypophyseal portal system. These hormones synergistically stimulate systemic ACTH secretion, which, in turn, stimulates the adrenal cortexes to secrete glucocorticoids. Central activation of the sympathetic neurons leads to activation of both the systemic sympathetic nervous system and, through the splanchnic nerves, the adrenal medullae (3). As the proper functioning of both the HPA axis and the sympathetic nervous system is crucial for survival and maintenance of health, it is not surprising that their regulation is developmentally plastic and complex, multilevel, and redundant. The regulation and central interaction of the HPA axis and the sympathetic nervous system and the immune system have been extensively studied and summarized in recent review articles (1, 3-5). The purpose of this brief review is to outline and discuss recent advances in the interactions and regulation of the adjacent peripheral limbs of the stress system, particularly the adrenal cortex and medulla, and to point out their implications for clinical endocrinology (Fig. 1).The adrenal gland has an astonishing capacity to adapt to various forms of acute and chronic stress (6 -8). After central activation of the HPA axis, ACTH triggers a physiologic, molecular, and morphological response of the adrenal cortex. This leads not only to glucocorticoid release, but also to up-regulation of steroidogenic cytochrome P 450 messenger ribonucleic acids (9, 10) and to conspicuous structural changes in the adrenal gland characterized by both hypervascularization and cellular hypertrophy and hyperplasia (11,12). These morphological changes are mirrored on the ultrastructural level; adrenocortical cells increase the number of their mitochondria, whereas their inner membranes form a dense vesi...

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“…DHEA is secreted mainly as its sulfoconjugate DHEA sulfate (DHEA-S), which is the most abundant circulating steroid hormone in both men and women. The divergence between the circulating levels of cortisol and both adrenal androgens (together referred to as DHEA(S)) observed during fetal and post-natal life suggests that the production of these steroids occurs, in part, through independent mechanisms (Parker & Odell 1980, McKenna et al 1997. This has led to speculation that hormones of extra-adrenal or intra-adrenal origin might selectively stimulate the production of DHEA(S).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Src tyrosine kinase stimulates adrenal androgen production

Sirianni

Carr²,

Andò

et al. 2003

Journal of Molecular Endocrinology

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A unique characteristic of the primate adrenal is the ability to produce 19-carbon steroids, often called the adrenal androgens. Although it is clear that the major human adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S), are produced almost solely in the adrenal reticularis, the mechanisms regulating production are poorly understood. Herein, we tested the hypothesis that the Src family of tyrosine kinases are involved in the regulation of adrenal androgen production. The NCI-H295R human adrenal cell line and primary human adrenal cells in culture were used to study adrenal androgen production and expression of enzymes involved in steroidogenesis. To examine the role of Src tyrosine kinase, cells were treated with PP2, a specific Src inhibitor. Alternatively, adrenal cells were transfected with an expression vector containing a dominant-negative form of Src. PP2 treatment inhibited basal cortisol production while significantly increasing the production of DHEA and DHEA-S (together referred to as DHEA(S)) in both adrenal cell models. The effect of PP2 on steroidogenesis occurred along with a rapid induction of steroidogenic acute regulatory (StAR) protein synthesis as revealed by Western analysis. Treatment with PP2 also increased mRNA levels for StAR, and cholesterol side-chain cleavage (CYP11A) and 17α-hydroxylase/17,20-lyase (CYP17) enzymes. Treatment of adrenal cells with the cAMP agonist dibutyryladenosine cyclic monophosphate (dbcAMP), stimulated the production of cortisol and DHEA(S). However, treatment of adrenal cells with a combination of PP2 and dbcAMP enhanced the production of DHEA(S) while inhibiting cortisol production. During dbcAMP treatment PP2 was able to augment the expression of CYP17 and to inhibit the induction of 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) levels. Increasing the CYP17 to HSD3B2 ratio is likely to promote the use of steroid precursors for the production of DHEA(S) and not for cortisol. Taken together these data suggest that the inhibition of Src tyrosine kinases causes adrenal cells to adopt a reticularis phenotype both by the production of DHEA(S) and by the steroidogenic enzymes expressed.

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2 A critical review of the origin and control of adrenal androgens

Cited by 47 publications

References 75 publications

Waist‐to‐Hip Ratio across Cultures: Trade‐Offs between Androgen‐ and Estrogen‐Dependent Traits

Waist‐to‐Hip Ratio across Cultures: Trade‐Offs between Androgen‐ and Estrogen‐Dependent Traits

Adrenocorticotropin (ACTH)- and Non-ACTH-Mediated Regulation of the Adrenal Cortex: Neural and Immune Inputs

Inhibition of Src tyrosine kinase stimulates adrenal androgen production

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