Studies on changes in the concentration of serum adrenal androgens in pubertal twins

Akamine, Yusuke; Kato, Kanefusa; Itoh, Hiroshi

doi:10.1530/acta.0.0930356

Cited by 31 publications

(17 citation statements)

References 10 publications

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“…There was no increase in the prevalence of balding in this U.S. population of male first-degree relatives. DHEAS levels were highly correlated between brothers and their proband sisters, consistent with a heritable trait (26)(27)(28)36). The same putative defect in steroidogenesis that we reported in the sisters of women with PCOS (12) could account for the observed DHEAS elevations in the brothers of PCOS probands.…”

Section: Discussionsupporting

confidence: 85%

“…There is a decline in circulating DHEAS levels with age (13,14,25), but this phenomenon was controlled for statistically in our analysis. Previous studies have suggested that there is a significant heritable component to circulating DHEAS levels in normal individuals (26)(27)(28). The heritability for DHEAS, however, has been found to be much less for men than for women (27), and heritability has also been noted to be stronger for T levels (26,27,29).…”

Section: Discussionmentioning

confidence: 98%

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Elevated Dehydroepiandrosterone Sulfate Levels as the Reproductive Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

Legro

Kunselman

Demers

et al. 2002

The Journal of Clinical Endocrinology &Amp; Metabolism

131

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There is an inherited susceptibility to polycystic ovary syndrome (PCOS). Some investigators have suggested that premature male-pattern balding is a male phenotype in PCOS families, but this remains controversial. We recently reported evidence for an autosomal monogenic abnormality in ovarian and adrenal steroidogenesis in the sisters of women with PCOS. We performed this study to determine whether we could identify a clinical or biochemical phenotype in the brothers of women with PCOS. One hundred nineteen brothers of 87 unrelated women with PCOS and 68 weight-and ethnicity-comparable unrelated control men were examined and had fasting blood samples obtained. The odds of balding (Hamilton score ≥ V) did not differ in the brothers of PCOS women compared with control men. Brothers of women with PCOS had significantly elevated dehydroepiandrosterone sulfate (DHEAS) levels [brothers 3035 ± 1132 ng/ml (mean ± SD) vs. control men 2494 ± 1172 ng/ml; P < 0.05]. There was a significant positive linear relationship between DHEAS levels in PCOS probands and their brothers (r = 0.35; P = 0.001). There was no significant bimodal distribution in DHEAS levels, and there were no significant differences in other parameters in brothers of PCOS women with high DHEAS levels compared with those with low DHEAS levels. There is familial clustering of elevated DHEAS levels in the brothers of women with PCOS, suggesting that this is a genetic trait. This might reflect the same underlying defect in steroidogenesis that we found in the sisters of women with PCOS. Balding was not increased in the brothers of women with PCOS. We conclude that there is a biochemical reproductive endocrine phenotype in men in PCOS families.Polycystic Ovary Syndrome (PCOS) is among the most common endocrinopathies of premenopausal women, affecting 5-10% of this population (1, 2). The syndrome is characterized by hyperandrogenism and chronic anovulation in the absence of specific Copyright © 2002 HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript disorders of the pituitary, ovaries, or adrenal glands (3). Familial aggregation of PCOS consistent with a genetic etiology has been well documented (4, 5). The male reproductive phenotypes that have been proposed in PCOS families include abnormalities in hair distribution, such as increased hair growth (6), and more commonly balding (7-10). This latter phenotype has been further refined to premature male balding defined as balding onset with an age of less than 30 yr (9, 10). Others have noted abnormalities in LH levels in male members of PCOS kindreds (11).We recently reported elevated T and dehydroepiandrosterone levels in the sisters of women with PCOS (12). There was a bimodal distribution of biologically available T levels in these sisters consistent with a monogenic trait controlled by alleles of a gene at an autosomal locus (12). If there was variation in such a gene regulating steroidogenesis, it was our hypothesis that this should result in a reproductive phen...

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 98%

Elevated Dehydroepiandrosterone Sulfate Levels as the Reproductive Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

Legro

Kunselman

Demers

et al. 2002

The Journal of Clinical Endocrinology &Amp; Metabolism

131

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“…Various data support the fact that inheritance plays a significant role in determining the circulating AA levels in normal individuals [93][94][95][96]. Circulating AA levels and their response to ACTH are highly individualized, compared to their secretion of glucocorticoids in normal women [97].…”

Section: Heritability Of Adrenal Steroidogenesis In Pcosmentioning

confidence: 95%

The adrenal and polycystic ovary syndrome

Yildiz

Azziz

2007

Rev Endocr Metab Disord

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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“…Enfin la survenue de cas familiaux de pubarche pr6coce [63], la plus grande similarit~ du timing et du d6veloppement de l'adr6narche observ6e chez les jumeaux monozygotes que chez les jumeaux dizygotes [2], et le fait que chez les enfants pr6-sentant un retard pubertaire simple, le retard d'adr6narche n'est qu'une des composantes d'un retard de croissance et de d~veloppement, sugg6rent fortement que la maturation du cortex surr~nal est, en partie tout au moins, sous le contr61e de facteurs g~n~tiques.…”

Section: Relations Entre Adrenarche Et Gonadarcheunclassified

La puberté surrénalienne

Forest

1997

Androl.

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RESUMELa surr~nale produit surtout des stdroides de la voie 45, la d~hydro~piandro-st~rone (DHA) et son sulfate (DHAS). Leurs taux tr~s ~lev~s ~ la naissance, d~croissent rapidement les premiers mois de vie, et sont tr~s bas de 1 ~ 6 an.q. Ils augmentent abruptement vers 7-8 ans dans les deux sexes, et vers 9-11 ans, avant tout signe de pubert~ gonadique, DHA et DHAS ont augment6 d'un facteur 10 et 20 respectivement, alors que la s~cr~tion du cortisol ne change pas. C'est la p~riode pr~-et parapubertaire des changements de biosynth6se des androgbnes surr~naliens que l'on individualise comme pubertd surrdnalienne ou adrdnarche. Elle est contemporaine du d~veloppement progressif de la zone r~ticul~e du cortex surr~nal et de l'activation du complexe enzymatique 17a-hydroxylase/17,20-1yase (P450c17) au d~triment de la 3fl-hydroxyst~roide d~shydrogdnase. L'adr~narche est un ph~nom~ne caractdristique de l'espbce humaine. A l'exception du chimpanz~, elle ne s'observe chez aucun autre mammif6re. Les facteurs responsables de l'adr~narche sont toujours mal connus. L'existence d'une r~gulation propre de la biosynthbse des androgbnes a ~td postulle. Plusieurs hypotheses ont ~t~ invoqu~es (inhibition de la 3B-ol par les ~estrog6nes ovariens, effet stimulant des gonadotrophines, de la GH ou de la prolactine) et r~fut~es ~ mesure que ronto. g~nie des s~cr~tions pubertaires se pr~-cisait. L'ACTH est un facteur trophique indispensable ~ une s~cr~tion normale d'androg~nes. La dissociation entre la r~ponse des s6cr~tions androgfiniques et celle du cortisol ~ I'ACTH a fait sugg~rer l'existence d'un facteur additionnel I'ACTH. L~hypoth~se que le CASH (cortical androgen-stimulating hormone) soit un segment de la pro-opiom~lanocortine attend confirmation. On a aussi invoqu~ l'effet des variations de gradient du cortisol intra-surr~nalien. Les facteurs g~ndtiques joueraient un certain r61e.En terme de d~veloppement le r61e de l'adr~narche apparait bien modeste. L'administration prolong~e de DHAS ou de DHA chez des enfants pr~sentant un retard d'adr~narche a montrd qu'ils n'avaient pas de r61e ddterminant sur la croissance somatique pr~pubertaire et le d~clenchement de la pubertY, et fait remettre en cause le concept classique qu'ils soient par eux-m~mes responsables de la pousse des poils sexuels. L'adr~-narche peut ~tre vue comme un index de maturation corporelle. En effet, la DHA est une pro-hormone, accessible au m~ta-bolisme p~riph~rique dans un grand nombre de tissus, dont le cerveau. Un 165 certain nombre de ses actions pourraient en d4river, en particulier celles qui sont li4es ~ la lutte contre le vieillissement.Enfin, des 4tudes 4pid4miologiques r4centes sugg~rent que des taux circulants bas de DHAS sont corr41~s avec une augmentation du taux de morbidit4 cardio-vasculaire chez l'homme ou de cancer du sein chez la femme. II n'est pas encore possible de conclure sur l'importance biologique de ces associations, et que les androgbnes surr4naliens soient une fontaine de jouvence, d'autant que la DHA peut avoir un r61e tout ~ fait i...

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Studies on changes in the concentration of serum adrenal androgens in pubertal twins

Cited by 31 publications

References 10 publications

Elevated Dehydroepiandrosterone Sulfate Levels as the Reproductive Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

Elevated Dehydroepiandrosterone Sulfate Levels as the Reproductive Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

The adrenal and polycystic ovary syndrome

La puberté surrénalienne

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