Stability of Adrenocortical Steroidogenesis over Time in Healthy Women and Women with Polycystic Ovary Syndrome

Yildiz, Bülent O.; Woods, Keslie S.; Stanczyk, Frank Z.; Bartolucci, A. A.; Azziz, Ricardo

doi:10.1210/jc.2004-0934

Cited by 29 publications

(22 citation statements)

References 40 publications

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“…3) [97]. Furthermore, in PCOS the within-subject responses of DHEA, A4 or F to ACTH stimulation remain relatively unchanged over time [100]. Taken together, these data suggest that ACTH-stimulated AA secretion is highly individualized, but relatively constant within individuals, consistent with the behavior of an inherited factor.…”

Section: Heritability Of Adrenal Steroidogenesis In Pcosmentioning

confidence: 61%

The adrenal and polycystic ovary syndrome

Yildiz

Azziz

2007

Rev Endocr Metab Disord

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115

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Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders characterized by androgen excess, oligo-ovulation and polycystic ovaries. Although ovaries are the main source of increased androgens in the syndrome, between 20 and 30% of patients with PCOS have adrenal androgen (AA) excess, detectable primarily by elevated dehydroepiandrosterone sulfate (DHEAS) levels. Patients with PCOS demonstrate a generalized hypersecretion of adrenocortical products, basally and in response to ACTH stimulation. The mechanisms of these abnormalities are unclear although AA excess in PCOS is likely a complex trait, modulated by both intrinsic and acquired factors. To date, no specific genetic defects have been identified. The production of AAs in response to ACTH appears to be closely related to altered factors regulating glucose-mediated glucose disposal, increased peripheral metabolism of cortisol, and to a less extent to the effects of extra-adrenal androgens, insulin resistance, hyperinsulinemia or obesity. Finally, DHEAS levels and the response of AAs to ACTH are relatively constant over time and are closely correlated between PCOS patients and their siblings suggesting that this abnormality is an inherited trait in PCOS.

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Section: Heritability Of Adrenal Steroidogenesis In Pcosmentioning

confidence: 61%

The adrenal and polycystic ovary syndrome

Yildiz

Azziz

2007

Rev Endocr Metab Disord

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115

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“…menopause and aging) , or associated female endocrinopathies involving an overproduction of DHEA (i.e. polycystic ovary syndrome) (Azziz et al 1998, Yildiz et al 2004. Likewise, deciphering the differences between Old World and New World primate adrenal and general biology provides greater insight into the appropriate usage of these animals as models for human disease.…”

Section: Discussionmentioning

confidence: 99%

Gender and gonadal status differences in zona reticularis expression in marmoset monkey adrenals: Cytochrome b5 localization with respect to cytochrome P450 17,20-lyase activity

Pattison

Saltzman

Abbott

et al. 2007

Molecular and Cellular Endocrinology

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Neonatal marmosets express an adrenal fetal zone comparable to humans. While adult males fail to express a functional ZR, with barely detectable blood DHEA levels, females produce higher levels of DHEA than males in adulthood. We investigated the presence of a putative functional ZR in adult female marmosets. In contrast to males, immunohistochemical analysis showed the ZR marker cytochrome b5 was elevated in the innermost zone in cycling females (compared to testis-intact males), further elevated in the adrenals from anovulatory females, and substantially elevated and continuous in ovariectomized females. As a functional test in vivo, following overnight dexamethasone treatment, cycling and anovulatory females showed higher levels of DHEA relative to males, but DHEA failed to increase in response to ACTH. In direct contrast, while ovariectomized females exhibited lower initial DHEA levels, clear increases were detectable after ACTH administration (p<0.05), suggesting an adrenal origin. The apparent differences in cytochrome b5 expression between groups were also further verified by western blotting of adrenal microsomes, and compared to 17,20-lyase activity; the two parameters were positively correlated (p<0.01) across multiple treatment groups. We conclude that the cycling female marmoset expresses a rudimentary ZR with at least a capacity for DHEA production that becomes significantly ACTH-responsive after anovulation. Expression of cytochrome b5 in this region may be directly or indirectly controlled by gonadal function, and is, at least in part, a critical determinant in the development of an adrenal ZR that is more defined and significantly ACTH-responsive.

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“…In some studies the calculation as proposed by Sodergard is used and validated by referencing to validation experiments in which the Vermeulen calculation is used (24,31,43 ).…”

Section: Emadi-konjin Et Al (20 ) and Morris Et Al (21 )mentioning

confidence: 99%

“…Calculated FT and bioT concentrations, most often obtained with the Vermeulen (15,(23)(24)(25)(26)(27)(28) and Sodergard (24,[29][30][31][32][33] methods, are used widely in the endocrinology literature. In most publications no arguments are given for the choice of a particular method for calculating FT or bioT although, as described above, choosing a particular set of constants will obviously influence results of calculated free and bioavailable hormone concentrations and thus might influence results of analyses.…”

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confidence: 99%