Adrenarche – physiology, biochemistry and human disease

Auchus, Richard J.; Rainey, William E.

doi:10.1046/j.1365-2265.2003.01858.x

Cited by 259 publications

(165 citation statements)

References 90 publications

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“…Circulating levels of DHEAS increase during foetal life, but decline rapidly after birth and remain low during early childhood, gradually increasing from about the age of 6 years (adrenarche) through puberty and reaching a peak in early adult life, followed by a continuous decline with age (Auchus and Rainey, 2004). Dehydroepiandrosterone sulphate can be converted both to more potent androgens and to oestrogens (Ibanez et al, 2000;Nicolas Diaz-Chico et al, 2007), but its physiological role is unclear and has been hypothesised to depend on the hormonal milieu (Ebeling and Koivisto, 1994).…”

Section: Discussionmentioning

confidence: 99%

Association of size at birth with adolescent hormone levels, body size and age at menarche: relevance for breast cancer risk

et al. 2008

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Birth size has been positively associated with age at menarche and height in adolescence and adulthood, but the relevant biological mechanisms remain unclear. Among 262 Norwegian term-born singleton girls, birth size measures (weight, length, ponderal index, head circumference and subscapular skin-fold thickness) were analysed in relation to adolescent hormone levels (oestradiol, prolactin, dehydroepiandrosterone sulphate, androstenedione and free testosterone index), age at menarche and adolescent (ages 12.7 -15.5 years) and body size (height, weight, body mass index and waist-to-hip ratio) using survival analysis and general linear modelling. The results were adjusted for gestational age at birth, age and menarcheal status at measurement in adolescence and maternal age at menarche. Birth weight, birth length and head circumference were positively associated with adolescent weight and height, and small birth size was associated with earlier age at menarche. Subscapular skin-fold thickness at birth was not associated with adolescent body size, but low fold-thickness was associated with earlier age at menarche. Measures of birth size were inversely related to circulating levels of dehydroepiandrosterone sulphate in adolescence, but there was no clear association with other hormones. These results suggest that physical and sexual development in puberty and adolescence is influenced by prenatal factors, and in combination, these factors may influence health and disease later in life. (Trichopoulos, 1990) has stimulated studies of birth size in relation to risk factors for BC (Okasha et al, 2003). Birth size is an indicator of foetal growth and may reflect intrauterine exposure to oestrogen, the key factor that was originally proposed to explain a possible association between intrauterine factors and adult BC (Trichopoulos, 1990). Studies have shown that relatively large birth size is associated with later age at menarche (Adair, 2001;Sloboda et al, 2007) and taller body height, both in adolescence (Pietiläinen et al, 2001;Romundstad et al, 2003) and in adulthood (Loos et al, 2002). Adult tallness is associated with higher BC risk, and the positive association between birth size and body height suggests that longitudinal growth in childhood and adolescence may be important determinants for subsequent BC (Michels and Willett, 2004). Birth size has also been inversely related to adrenal androgen production during childhood (Ong et al, 2004) and adolescence (Ibanez et al, 1999). Adult levels of both adrenal and gonadal androgens have been associated with BC risk (Kaaks et al, 2005a, b). The fact that small birth size is associated with earlier age at menarche and higher circulating levels of adrenal androgens cannot be easily reconciled with known BC risk factors, as small birth size may be related to reduced risk, and both early age at menarche and androgens are expected to increase risk.We have examined the relation between birth size characteristics and potential BC risk factors (ESHRE Capri Workshop Group, 2004),...

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Section: Discussionmentioning

confidence: 99%

Association of size at birth with adolescent hormone levels, body size and age at menarche: relevance for breast cancer risk

et al. 2008

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“…A further round of oxidative conversion of the hydroxylated form by CYP17 to form DHEA occurs in the zona reticularis but is absent from the zona fasciculata. Moreover, the dual activities of CYP17 in the zona reticularis are temporally expressed during the lifespan of an individual in a phenomenon known as adrenarche (Auchus & Rainey 2004).…”

Section: Role Of Cyp17 In Human Adrenal Cortex Physiologymentioning

confidence: 99%

Cytochrome b5 modulation of 17α hydroxylase and 17–20 lyase (CYP17) activities in steroidogenesis

Akhtar¹,

Kelly²,

Kaderbhai³

2005

Journal of Endocrinology

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CYP17 is a steroidogenic enzyme located in the zona fasciculata and zona reticularis of the adrenal cortex and gonad tissues and which has dual functions -hydroxylation and as a lyase. The first activity gives hydroxylation of pregnenolone and progesterone at the C 17 position to generate 17 -hydroxypregnenolone and 17 -hydroxyprogesterone, while the second enzymic activity cleaves the C 17 -C 20 bond of 17 -hydroxypregnenolone and 17 -hydroxyprogesterone to form dehydroepiandrosterone and androstenedione respectively. The modulation of these two activities occurs through cytochrome b 5 . Association of cytochrome b 5 and CYP17 is thought to be based primarily on electrostatic interactions in which the negatively charged residues pair up with positively charged residues on the proximal surface of the CYP17 molecule. Non-specific interactions of the hydrophobic membrane regions of cytochrome b 5 and CYP17 are also thought to play a crucial role in the association of these two haemoproteins. Although cytochrome b 5 is known to stimulate CYP activity by contributing the second electron in the catalytic cycle, in the case of CYP17, the mechanism of cleavage stimulation proceeds via an allosteric mode. It is hypothesised that cytochrome b 5 promotes the cleavage by aligning the iron-oxygen complex attack onto the C 20 rather than the C 17 atom of the steroid substrate molecule. Thus, further understanding of the mechanism of modulation by cytochrome b 5 of the hydroxylase and lyase activities should shed new insights on developing therapeutic targets in CYP17-linked biochemical processes such as adrenarche, polycystic ovary syndrome and prostate cancer.

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“…Since DHEA and DHEAS are weak or inactive as androgens, peripheral conversion of these steroids to testosterone and, subsequently dihydrotestosterone (DHT) is necessary to promote androgen-dependent hair growth in girls (6). It is apparent that adrenal androgens, independent of gonadal androgens, may drive axillary and pubic hair development, which is proven by a series of cases demonstrating the growth of androgen-dependent hair in the absence of gonadal steroids and conversely demonstrating the absence of pubarche in girls with adrenal insufficiency (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Puberty in a case with novel 17-hydroxylase mutation and the putative role of estrogen in development of pubic hair

Turan¹,

Bereket²,

Güran³

et al. 2009

European Journal of Endocrinology

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Objective: 17-Hydroxylase/17,20-lyase deficiency (17OHD) results from mutations in the CYP17A1 gene, leading to failure to synthesize cortisol, adrenal androgens, and gonadal steroids. Adrenarche is a consequence of the increased production of adrenal androgens. Here, we report a case carrying novel R239Q mutation causing complete functional loss of CYP17A1, and thus absence of adrenal and gonadal sex hormone production. The patient has had unexpected pubic hair development and insufficient breast development with estrogen replacement therapy. Possible mechanisms leading to pubic hair development and breast underdevelopment are discussed. Patient and methods: A 15-year-old female born to consanguineous parents presented with the lack of full breast development and irregular menses after the age of 14 years. She had Tanner III breast development on one side, Tanner I on the other side and Tanner I pubic hair and, no axillary hair development. The serum levels of FSH, LH, and progesterone were high and, estradiol was low. The measurement of basal and ACTH-stimulated steroids was consistent with the diagnosis of 17OHD. Genetic analysis revealed novel homozygous mutation R239Q in CYP17A1 gene. Therapy with hydrocortisone was initiated and followed by the addition of conjugated estrogen. Her breast development did not improve considerably, however, pubic hair development started after estrogen treatment in spite of undetectable serum levels of androgens. Conclusion: This case study suggests that estrogen exerts a permissive effect on pubic hair development in girls, even in the presence of very low-circulating androgens, and impaired breast development might be due to estrogen/progesterone imbalance in breast tissue.

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Adrenarche – physiology, biochemistry and human disease

Cited by 259 publications

References 90 publications

Association of size at birth with adolescent hormone levels, body size and age at menarche: relevance for breast cancer risk

Association of size at birth with adolescent hormone levels, body size and age at menarche: relevance for breast cancer risk

Cytochrome b5 modulation of 17α hydroxylase and 17–20 lyase (CYP17) activities in steroidogenesis

Puberty in a case with novel 17-hydroxylase mutation and the putative role of estrogen in development of pubic hair

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