Size matters: Associations between the androgen receptor CAG repeat length and the intrafollicular hormone milieu
Language English Country Ireland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26404660
DOI
10.1016/j.mce.2015.09.015
PII: S0303-7207(15)30081-2
Knihovny.cz E-resources
- Keywords
- Androgen levels, Androgen receptor, CAG repeats, Follicular fluid, Human small antral follicles,
- MeSH
- Receptors, Androgen genetics MeSH
- Aromatase genetics MeSH
- Adult MeSH
- Trinucleotide Repeat Expansion * MeSH
- Follicular Fluid cytology metabolism MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Gonadal Hormones genetics metabolism MeSH
- Receptors, LH genetics MeSH
- Gene Expression Profiling methods MeSH
- Testosterone metabolism MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Receptors, Androgen MeSH
- AR protein, human MeSH Browser
- Aromatase MeSH
- CYP19A1 protein, human MeSH Browser
- Gonadal Hormones MeSH
- Receptors, LH MeSH
- Testosterone MeSH
Granulosa cell (GC) expressed androgen receptors (AR) and intrafollicular androgens are central to fertility. The transactivating domain of the AR contains a polymorphic CAG repeat sequence, which is linked to the transcriptional activity of AR and may influence the GC function. This study aims to evaluate the effects of the AR CAG repeat length on the intrafollicular hormone profiles, and the gene expression profiles of GC from human small antral follicles. In total, 190 small antral follicles (3-11 mm in diameter) were collected from 58 women undergoing ovarian cryopreservation for fertility preservation. The biallelic mean of the CAG repeat lengths were calculated for each woman, and grouped in three groups: Long CAG repeats (23-26 mean CAG); medium CAG repeats (20.5-22.5 mean CAG) and short CAG repeats (17.5-20.0 mean CAG). The following parameters were measured: follicle diameter, intrafollicular levels of Anti-Müllerian Hormone (AMH), progesterone, oestradiol, testosterone and androstenedione, and GC gene expression levels of FSHR, LHR, AR, CYP19A1, and AMH. The long CAG repeat lengths were associated with significantly decreased testosterone levels, as compared to medium CAG repeats (P = 0.05) and short CAG repeats (P = 0.003). Furthermore, in follicles 3-6 mm in diameter, the long CAG repeats were associated with significantly increased LHR and CYP19A1 gene expression levels compared to short CAG repeat lengths (P = 0.004 and P = 0.04 respectively), and significantly increased LHR expression compared to medium CAG repeat lengths (P = 0.03). In conclusion, long CAG repeat lengths in the AR were associated to significant attenuated levels of androgens and an increased conversion of testosterone into oestradiol, in human small antral follicles.
Department of Biomedicine University of Aarhus Aarhus Denmark
Laboratory of Reproductive Biology Rigshospitalet Copenhagen Denmark
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