Adrenarche: Postnatal Adrenal Zonation and Hormonal and Metabolic Regulation

Belgorosky, Alicia; Baquedano, María Sonia; Guercio, Gabriela; Rivarola, Marco A.

doi:10.1159/000157871

Cited by 60 publications

(47 citation statements)

References 140 publications

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“…It should also be recognized that adrenal androgen secretion of physiological significance is not unique to primates (Boonstra et al 2011) and may be very transient in other species (Pignatelli et al 2006). Adrenarche has been the subject of numerous reviews (Parker et al 1978, Havelock et al 2004, Campbell 2006, 2011, Nader 2007, Belgorosky et al 2008, Miller 2009, Conley et al 2011a) but seldom has the evidence for or against its occurrence in the NHP been reviewed objectively.…”

Section: Clinical Significance Of Adrenarchementioning

confidence: 99%

Adrenarche in nonhuman primates: the evidence for it and the need to redefine it

Conley¹,

Bernstein²,

Nguyen³

2012

Journal of Endocrinology

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Adrenarche is most commonly defined as a prepubertal increase in circulating adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfo-conjugate (DHEAS). This event is thought to have evolved in humans and some great apes but not in Old World monkeys, perhaps to promote brain development. Whether adrenarche represents a shared, derived developmental event in humans and our closest relatives, adrenal androgen secretion (and its regulation) is of considerable clinical interest. Specifically, adrenal androgens play a significant role in the pathophysiology of polycystic ovarian disease and breast and prostate cancers. Understanding the development of androgen secretion by the human adrenal cortex and identifying a suitable model for its study are therefore of central importance for clinical and evolutionary concerns. This review will examine the evidence for adrenarche in nonhuman primates (NHP) and suggest that a broader definition of this developmental event is needed, including morphological, biochemical, and endocrine criteria. Using such a definition, evidence from recent studies suggests that adrenarche evolved in Old World primates but spans a relatively brief period early in development compared with humans and some great apes. This emphasizes the need for frequent longitudinal sampling in evaluating developmental changes in adrenal androgen secretion as well as the tenuous nature of existing evidence of adrenarche in some species among the great apes. Central to an understanding of the regulation of adrenal androgen production in humans is the recognition of the complex nature of adrenarche and the need for more carefully conducted comparative studies and a broader definition in order to promote investigation among NHP in particular.

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Section: Clinical Significance Of Adrenarchementioning

confidence: 99%

Adrenarche in nonhuman primates: the evidence for it and the need to redefine it

Conley¹,

Bernstein²,

Nguyen³

2012

Journal of Endocrinology

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“…[175][176][177] IGF-1 stimulates 5α-reductase, adrenal and gonadal androgen synthesis, AR signal transduction, sebocyte proliferation and lipogenesis. [178][179][180][181][182][183][184] Milk consumption results in a significant increase in IGF-1 serum level and exerts strong insulinotropic effects comparable to high glycaemic food. 185,186 Insulin induces hepatic IGF-1 secretion, and both hormones amplify the stimulatory effect of GH on sebocytes and augment mitogenic downstream signaling pathways of insulin receptors, IGF-1 receptor and FGFR2b (Fig.…”

Section: Interleukin-1α Network In Keratinocytesmentioning

confidence: 99%

Role of FGFR2-signaling in the pathogenesis of acne

Melnik

2009

Dermato-Endocrinology

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It is the purpose of this review to extend our understanding of the fibroblast growth factor (FGF) receptor-2b-signaling network in the pathogenesis of acne. A new concept of the role of FGFR2b-signaling in dermal-epithelial interaction for skin appendage formation, pilosebaceous follicle homeostasis, comedogenesis, sebaceous gland proliferation and lipogenesis is presented. The FGFR2-gain-of-function mutations in Apert syndrome and unilateral acneiform nevus are most helpful model diseases pointing the way to androgen-dependent dermalepithelial FGFR2-signaling in acne. Androgen-mediated upregulation of FGFR2b-signaling in acne-prone skin appears to be involved in the pathogenesis of acne vulgaris. In organotypic skin cultures, keratinocyte-derived interleukin-1α stimulated fibroblasts to secrete FGF7 which stimulated FGFR2b-mediated keratinocyte proliferation. Postnatal deletion of FGFR2b in mice resulted in severe sebaceous gland atrophy. The importance of FGFR2b in sebaceous gland physiology is further supported by the mode of action of anti-acne agents which have been proposed to attenuate FGFR2b-signaling. Downregulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Downregulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity. Insulin-like growth factor-1 (IGF-1), the mediator of growth hormone during puberty, intracts with androgen-dependent FGFR2b-signaling and links androgen-and FGF-mediated signal transduction important in sebaceous gland homeostasis. The search for a follicular defect in the dermalepithelial regulation of growth factor-signaling in acne-prone skin appears to be a most promising approach to clarify the pathogenesis of acne.

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“…During fetal development, large amounts of DHEA and DHEAS are produced, but the production decreases rapidly after birth (1,2). The re-activation of the adrenal androgen production has been observed as early as 3 years of age and seems to be a gradual and ongoing process under ACTH stimulation (3,4).…”

Section: Introductionmentioning

confidence: 99%

The pubertal transition in 179 healthy Danish children: associations between pubarche, adrenarche, gonadarche, and body composition

Mouritsen

Aksglæde

Soerensen

et al. 2013

European Journal of Endocrinology

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Background: Pubertal onset is usually defined by breast development in girls and testicular growth in boys. Pubarche is defined as the attainment of pubic hair and is considered as a sign of pubertal transition. Pubarche is preceded by a gradual increase in production of adrenal androgens, DHEA and D4-androstenedione (Adione), a process termed adrenarche. Objective: To study the natural course of pubertal transition and the associations with adrenarche, body fat, and linear growth. Design and methods: A longitudinal study of 179 healthy children (89 girls) with higher socioeconomic background examined every 6 months for 5 years. Pubic hair stage, breast stage, genital stage, testicular volume (TV), height, weight, and four skinfolds were measured. Results: In girls, median age (25th and 75th percentiles) at thelarche (B2C) was 10.1 years (9.3-10.9). In boys, median age at attaining a TV O3 ml was 11.5 years (10.9-12.0). Median age at pubarche (PH2C) was 10.9 years (10.3-11.4) in girls and 11.6 years (10.8-12.4) in boys. Only 6.8% (4/59) of the girls and 24.6% (15/61) of the boys developed pubic hair as the first isolated sign of puberty. Serum DHEAS and Adione increased with age, although the increase in Adione was most pronounced in girls. No associations between early age at thelarche/testicular growth and increased body fat (BMI and sum of four skinfolds) were observed. Conclusion: Danish children rarely experience pubarche as the first sign of puberty. No associations between age at pubertal onset and body composition were found. Circulating levels of Adione, but not DHEAS, increased with the onset of puberty, although with large interindividual variability.

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Adrenarche: Postnatal Adrenal Zonation and Hormonal and Metabolic Regulation

Cited by 60 publications

References 140 publications

Adrenarche in nonhuman primates: the evidence for it and the need to redefine it

Adrenarche in nonhuman primates: the evidence for it and the need to redefine it

Role of FGFR2-signaling in the pathogenesis of acne

The pubertal transition in 179 healthy Danish children: associations between pubarche, adrenarche, gonadarche, and body composition

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