Steroidogenic alterations and adrenal androgen excess in PCOS

Doi, Suhail A.R.; Al-Zaid, Mona; Towers, Philip A.; Scott, Christopher J.; Al-Shoumer, Kamal A.S.

doi:10.1016/j.steroids.2006.05.005

Cited by 33 publications

(35 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This hypothesis agrees with a 3-4% decrease in the efficiency of cortisol biosynthesis in the zona fasciculata (derived from the increased ratio of corticosterone to cortisol at 60 min after ACTH administration; 34) of prenatally androgenized female monkeys, as well as an ∼14-fold increase in corticosterone versus an ∼8-fold increase in cortisol following ACTH administration (31). While enhanced 3beta-HSD II activity exists in some PCOS women with adrenal androgen excess (36), it is unclear whether this phenomenon translates into corticosterone hyperresponsiveness to ACTH in humans.…”

Section: Adrenal Hyperandrogenism In Adult Prenatally Androgenized Mosupporting

confidence: 74%

Fetal Programming of Adrenal Androgen Excess: Lessons from a Nonhuman Primate Model of Polycystic Ovary Syndrome

Abbott¹,

Zhou²,

Bird

et al. 2008

Disorders of the Human Adrenal Cortex

View full text Add to dashboard Cite

Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of DHEAS, typical of PCOS women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the 17-hydroxyprogesterone response and reducing the DHEA to 17-hydroxyprogesterone ratio. Since 60-min post-ACTH serum values for 17-hydroxyprogesterone correlate negatively with basal serum insulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys. Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS.

show abstract

Section: Adrenal Hyperandrogenism In Adult Prenatally Androgenized Mosupporting

confidence: 74%

Fetal Programming of Adrenal Androgen Excess: Lessons from a Nonhuman Primate Model of Polycystic Ovary Syndrome

Abbott¹,

Zhou²,

Bird

et al. 2008

Disorders of the Human Adrenal Cortex

View full text Add to dashboard Cite

show abstract

“…Higher baseline levels of DHEAS and 17-OHPE in hyperandrogenic patients also indicate higher P45017α complex activity in the Δ5 pathway. These observations are relevant because, in normal conditions, the human P450c17α enzyme possesses normal 17,20 lyase activity for the conversion of 17-OHPE to DHEA (Δ5 pathway) but minimal, if any, activity for the conversion of 17-OHP4 to A (Δ4 pathway) (26). Compared to healthy individuals, greater activity of 17,20 lyase was previously demonstrated in PCOS patients when they were diagnosed according to the Rotterdam criteria and taken as the only population group (14).…”

Section: Discussionmentioning

confidence: 99%

“…Hyperandrogenic patients may present decreased 3β-HSDII activity with a lower conversion rate of Δ5-3β-hydroxysteroids to Δ4-3β-hydroxysteroids (10,11), which results in a higher amount of substrates for androgen synthesis (26,27). Prior to the NIH/Rotterdam criteria, a non-classic clinical form of 3β-HSD deficiency was reported in hyperandrogenic patients with hirsutism and abnormal menstrual cycles (27,28), and different 3β-HSD activities have been reported in PCOS patients both before (27) and after the implementation of the Rotterdam criteria (26).…”

Section: Discussionmentioning

confidence: 99%

“…Prior to the NIH/Rotterdam criteria, a non-classic clinical form of 3β-HSD deficiency was reported in hyperandrogenic patients with hirsutism and abnormal menstrual cycles (27,28), and different 3β-HSD activities have been reported in PCOS patients both before (27) and after the implementation of the Rotterdam criteria (26). In the current study, normo-and hyperandrogenic PCOS patients demonstrated equal ratios of progesterones (17-OHP4/17-OHPE p = 0.837), suggesting equal 3β-HSDII activity in these groups for the conversion of 17-OHPE to 17-OHP4.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

New insights into steroidogenesis in normo- and hyperandrogenic polycystic ovary syndrome patients

Gil-Junior¹,

Barbosa

Isaías³

et al. 2013

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

Objective: This study sought to examine corticosteroidogenic enzyme activities in normo-and hyperandrogenic polycystic ovary syndrome (PCOS) patients. Subjects and methods: This cohort study included 81 patients with biochemical hyperandrogenism and 41 patients with normal androgen levels. Enzyme activities were assessed according to the serum steroid product/precursor ratios at baseline and after adrenal stimulation. Results: At baseline, in the delta 4 (Δ4) pathway, hyperandrogenic patients showed greater 17-hydroxylase and 17,20 lyase activities in converting progesterone (P4) into 17-hydroxyprogesterone (17-OHP4) and 17-hydroxypregnenolone (17-OHPE) into androstenedione (A) (p = 0.0005 and p = 0.047, respectively) compared to normoandrogenic patients. In the delta 5 (Δ5) pathway, the 17-hydroxylase and 17,20 lyase enzymes showed similar activities in both groups. Hyperandrogenic patients presented lower 21-hydroxylase, lower 11β-hydroxylase (p = 0.0001), and statistically significant increases in 3β-hydroxysteroid dehydrogenase II (3β-HSDII) activities (p < 0.0001). Following tetracosactrin stimulation, only the 17,20 lyase activity remained up--regulated in the Δ4 pathway (p < 0.0001). Conclusion: Hyperandrogenic patients had higher 17,20 lyase activity, both at baseline and after adrenal stimulation. Greater conversion of dehydroepiandrosterone (DHEA) into A with normal conversion of 17-OHPE to 17-OHP4 in hyperandrogenic PCOS patients indicated different levels of 3β-HSDII activity in adrenal cells, and hyperandrogenic patients had lower 11β-hydroxylase and 21-hydroxylase activities. Arq Bras Endocrinol Metab. 2013;57(6):437-44 Keywords Polycystic ovary syndrome; steroidogenesis; hyperandrogenism; enzyme activity; adrenal stimulation RESUMO Objetivo: O objetivo deste estudo foi examinar a atividade de enzimas responsáveis pela produção de corticosteroides em pacientes normo e hiperandrogênicas com síndrome de ovários policísticos (SOP). Sujeitos e métodos: A coorte estudada incluiu 81 pacientes com hiperandrogenismo bioquímico e 41 pacientes com níveis normais de androgênio. A atividade enzimática foi avaliada de acordo com as proporções de produto/precursor do esteroide sérico, no momento inicial do estudo e depois de estimulação adrenal. Resultados: No momento inicial, na via delta 4 (Δ4), as pacientes hiperandrogênicas mostraram maior atividade da 17-hidroxilase e 17,20 liase na conversão da progesterona (P4) em 17-hidroxiprogesterona (17-OHP4) e na conversão da 17-hidroxipregnenolona (17-OHPE) em androstenediona (A) (p = 0,0005 e p = 0,047, respectivamente) em comparação com pacientes normoandrogênicas. Na via delta 5 (Δ5), a 17-hidroxilase e a 17,20 liase mostraram atividades similares nos dois grupos. As pacientes hiperandrogênicas mostraram menor atividade da 21-hidroxilase, menor atividade da 11β-hidroxilase (p = 0,0001) e aumento estatisticamente significativo na atividade da 3β-hidroxiesteroide desidrogenase II (3β-HSDII) (p < 0.0001). Após a estimulação com tetracosactrin, apenas a ativi...

show abstract

“…3,[11][12][13]16 Because elevated androgens, such as dehydroepiandrosterone sulfate and testosterone (free and total), have been reported to associate with insulin resistance, 17 obesity, 18 and lipid metabolism 19 ; therefore, elevated androgens may raise the risk for cardiovascular disease. The present study demonstrated that the serum bioavailable and total testosterone levels were significantly and positively correlated with both SBP and DBP in young women with PCOS, independent of insulin resistance, obesity, and dyslipidemia.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Androgen Levels and Blood Pressure in Young Women With Polycystic Ovary Syndrome

et al. 2007

View full text Add to dashboard Cite

Abstract-The role of testosterone on the development of hypertension is controversial, especially in women with polycystic ovary syndrome (PCOS) who have higher prevalence of obesity and insulin resistance than women without PCOS. Little is known about the association between serum testosterone level and blood pressure in young women with PCOS. In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study, we measured the body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin, lipid profile, and hormone profiles. The free androgen index, total testosterone, and sex hormone-binding globulin, but not the level of dehydroepiandrosterone sulfate, significantly correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP). In multiple linear regression models adjusted for age, body mass index, and other anthropometric, metabolic, and hormonal variables, the level of serum free androgen index or total testosterone, but not the sex hormone-binding globulin, were independently related to SBP and DBP. The age-and body mass index-adjusted least-square mean of serum-free androgen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels. The high bioavailable testosterone levels (free androgen index: Ն19%) in women with PCOS increased the risk of elevated blood pressure (SBP Ն130 mm Hg and/or DBP Ն85 mm Hg) with an odds ratio of 3.817 (Pϭ0.029; 95% CI: 1.14 to 12.74) after adjustment for age, anthropometric measures, and metabolic profiles. Our results suggest that the characteristic hyperandrogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age, insulin resistance, obesity, or dyslipidemia. Key Words: polycystic ovary syndrome Ⅲ testosterone Ⅲ systolic blood pressure Ⅲ diastolic blood pressure Ⅲ hypertension W omen with polycystic ovary syndrome (PCOS) are characterized by clinical and/or biochemical hyperandrogenism, oligomenorrhea, and the presence of polycystic ovaries. 1 PCOS is a heterogenous medical condition. Because large individual variation is present with respect to hyperandrogenism in terms of clinical manifestations and biochemistry, not all women with PCOS have elevated testosterone levels. Indeed, some women with PCOS without elevated testosterone levels may have acne, hirsutism, and/or androgenic alopecia that may arise as a result of the elevated androgens secreted by adipose tissue and the adrenal glands rather than the testosterone secreted from the ovaries.Although the increased risk of atherosclerotic cardiovascular disease and hypertension in women with PCOS remains controversial, 2,3 a variety of intriguing metabolic disturbances related to the risk for cardiovascular disease and hypertension are commonly found in a large proportion of women with PCOS, such as obesity, insulin resistance, dyslipidemia, and the metabolic syndrome. 4 Women with PCOS have been reported to have reduced vascular compliance, 5 vascular endothelial...

show abstract

Steroidogenic alterations and adrenal androgen excess in PCOS

Cited by 33 publications

References 88 publications

Fetal Programming of Adrenal Androgen Excess: Lessons from a Nonhuman Primate Model of Polycystic Ovary Syndrome

Fetal Programming of Adrenal Androgen Excess: Lessons from a Nonhuman Primate Model of Polycystic Ovary Syndrome

New insights into steroidogenesis in normo- and hyperandrogenic polycystic ovary syndrome patients

Relationship Between Androgen Levels and Blood Pressure in Young Women With Polycystic Ovary Syndrome

Contact Info

Product

Resources

About