Decreased Androgen Receptor Gene Methylation in Premature Pubarche: A Novel Pathogenetic Mechanism?
Abstract
CONTEXT: Several studies found links between DNA methylation and gene expression. In patients with idiopathic hirsutism, a preferential methylation of the of shorter androgen receptor (AR) alleles was hypothesized to be responsible for the abnormal hair growth. OBJECTIVE: The objective of this study was to assess whether abnormalities in the AR function in both peripheral blood leukocytes (PBLs) and androgen target tissues are present in children with premature pubarche (PP). DESIGN: Human DNA was extracted from PBLs and pubic hair and CAG repeats length and methylation status of the AR gene were analyzed. SETTING: The study was performed at a Pediatric Endocrinology referral clinic. PATIENTS: Twenty-five girls with PP, 23 prepubertal children, and 10 girls with Tanner stage II pubertal development were studied. MAIN OUTCOME MEASURE: The main outcome measures were CAG repeat length and AR methylation pattern in PBLs and pubic hair. RESULTS: In PBLs from PP patients, AR gene methylation was significantly lower (P < 0.01) than that of prepubertal children and similar to that of girls with Tanner II stage pubertal development. A negative correlation between AR gene methylation in PBLs and the age of normal children was detected. PATIENTS with PP exhibited a hair follicle AR methylation pattern similar to that of Tanner stage II girls. The mean number of CAG repeats was lower in PP patients than in prepubertal and Tanner stage II girls, although it was within the normal range for the general population in both groups. CONCLUSIONS: The increased AR gene activity observed in PP patients, as indicated by the reduced AR gene methylation pattern, together with the presence of shorter CAG repeats, might lead to hypersensitivity of the hair follicles to steroid hormones and therefore to the premature development of pubic hair.
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Decreased methylation of the androgen receptor gene in hair follicles was shown to produce increased gene expression, more active androgen receptors, and increased sensitivity to androgens in children with IPP.
“In the latter, a decreased methylation of the androgen receptor gene in an androgen target tissue such as hair follicles was shown to produce an increased gene expression, and in turn, more active androgen receptors and increased sensitivity to androgens.”
From Relationship of CYP21A2 genotype and serum 17-hydroxyprogesterone and cortisol levels in a large cohort of Italian children with premature pubarche (2011) · cites this paper as [4]
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- Authors
- Vottero, A., Capelletti, M., Giuliodori, S., Viani, I., Ziveri, M., Neri, T. M., Bernasconi, S., & Ghizzoni, L.
- Affiliations
- University of Parma (IT)
- Ospedale di Parma (IT)
- Corresponding author
- Ghizzoni, L.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2006-03
- Volume
- 91
- Issue
- 3
- Pages
- 968-972
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2081880833
- Cited by
- 58
- References
- 27
- Citations by year
- 2025: 3 · 2023: 2 · 2021: 7 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 4 · 2014: 5 · 2012: 3
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- Università degli Studi di Parma
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- premature pubarche, androgen receptor, DNA methylation, CAG repeat length, idiopathic hirsutism, peripheral blood leukocytes, pubic hair, hair follicle, precocious puberty, pathogenesis
- MeSH terms
- Child, Female, Humans, Puberty, Precocious, Receptors, Androgen, Reference Values, Polymerase Chain Reaction, Hair Follicle, Trinucleotide Repeats, DNA Methylation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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