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Cited by 179Adrenal Hormones and DisordersSteroid Chemistry and BiochemistrySexual Differentiation and Disorders

Androgen biosynthesis from cholesterol to DHEA

Miller, Walter L·2002·Molecular and Cellular Endocrinology
DOI 10.1016/s0303-7207(02)00363-5
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Abstract

Androgens and estrogens are made from dehydroepiandrosterone (DHEA), which is made from cholesterol via four steps. First, cholesterol enters the mitochondria with the assistance of the steroidogenic acute regulatory protein (StAR). Mutations in the StAR gene cause congenital lipoid adrenal hyperplasia. Second, within the mitochondria, cholesterol is converted to pregnenolone by the cholesterol side chain cleavage enzyme, P450scc. Third, pregnenolone undergoes 17alpha-hydroxylation by microsomal P450c17. Finally, 17-OH pregnenolone is converted to DHEA by the 17,20 lyase activity of P450c17. The ratio of the 17,20 lyase to 17alpha-hydroxylase activity of P450c17 determines the ratio of C21 to C19 steroids produced. This ratio is regulated post-translationally by at least three factors: the abundance of the electron-donating protein P450 oxidoreductase, the presence of cytochrome b(5), and the serine phosphorylation of P450c17. Study of these and related factors may yield important information about the pathophysiology of adrenarche and the polycystic ovary syndrome (PCOS).

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Crossref · 10.1016/s0303-7207(02)00363-5

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  • Each month another follicle is recruited and stimulated by gonadotropins, presenting spontaneous breast development in affected girls.

    “Each month another follicle is recruited and stimulated by gonadotropins, presenting spontaneous breast development in affected girls26).”

    From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [26]

  • These steroid hormone levels are too low to suppress secretion of ACTH, gonadotropins, and angiotensin II.

    “However, these steroid hormone levels are too low to suppress secretion of adrenocorticotropic hormone (ACTH), gonadotropins, and angiotensin II26).”

    From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [26]

  • A severe defect in fetal testicular biosynthesis is evident because affected 46,XY genetic males are born with all female external genitalia, reflecting an absence of testosterone synthesis between 6 and 12 weeks of gestation.

    “A severe defect in fetal testicular biosynthesis is evident because affected 46,XY genetic males are born with all female external genitalia, reflecting an absence of testosterone synthesis between 6 and 12 weeks of gestation26).”

    From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [26]

  • Follicles that are not recruited remain unstimulated and constitute a reservoir of steroidogenic cells undamaged by the second hit of lipoid CAH, so a new undamaged follicle is recruited with each regular cycle, and estrogen is produced leading to cyclic uterine estrogen withdrawal bleeding that resembles a normal menstruation, but there is no progesterone, so these cycles are anovulatory.

    “Follicles that are not recruited remain unstimulated and constitute a reservoir of steroidogenic cells undamaged by the second hit of lipoid CAH, so a new undamaged follicle is recruited with each regular cycle, and estrogen is produced leading to cyclic uterine estrogen withdrawal bleeding that resembles a normal menstruation, but there is no progesterone, so these cycles are anovulatory26).”

    From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [26]

  • Unlike the testes and adrenal glands, the ovaries only start to make steroid hormones at the onset of puberty.

    “Unlike the testes and adrenal glands, the ovaries only start to make steroid hormones at the onset of puberty26).”

    From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [26]

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Authors
Miller, W. L.
Affiliations
University of California, San Francisco (US)
Corresponding author
Miller, Walter L
ORCID
Miller, Walter L
Venue
Molecular and Cellular Endocrinology
Publisher
Elsevier BV
Published
2002-12
Volume
198
Issue
1-2
Pages
7-14
ISSN
0303-7207 (ISSN-L)
DOI
10.1016/s0303-7207(02)00363-5
OpenAlex
W2080588524
Cited by
179
References
89
Citations by year
2026: 8 · 2025: 5 · 2024: 10 · 2023: 11 · 2022: 8 · 2021: 9 · 2020: 5 · 2019: 6 · 2018: 12 · 2017: 2 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 4 · 2012: 8
FWCI
2.63
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Molecular and Cellular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01dk042154-09)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-37922, DK 42154, R01DK037922)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD034449)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Keywords
androgen production, dehydroepiandrosterone, cholesterol, steroidogenic acute regulatory protein, congenital lipoid adrenal hyperplasia, cholesterol side-chain cleavage enzyme, P450scc, P450c17, pregnenolone, cytochrome P450 oxidoreductase, cytochrome b5, adrenarche, polycystic ovary syndrome
MeSH terms
Steroidogenic Acute Regulatory Protein, Adrenal Glands, Adrenal Hyperplasia, Congenital, Androgens, Animals, Cholesterol, Cholesterol Side-Chain Cleavage Enzyme, Dehydroepiandrosterone, Female, Humans, Lipidoses, Male, Mitochondria, Phosphoproteins, Polycystic Ovary Syndrome, Serine, Steroid 17-alpha-Hydroxylase

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