Part of the Interindividual Variation in Serum Testosterone Levels in Healthy Men Reflects Differences in Androgen Sensitivity and Feedback Set Point: Contribution of the Androgen Receptor Polyglutamine Tract Polymorphism

Crabbe, Patricia; Bogaert, Veerle; Bacquer, Dirk De; Goemaere, Stefan; Zmierczak, Hans‐Georg; Kaufman, Jean

doi:10.1210/jc.2007-0117

Cited by 124 publications

(133 citation statements)

References 32 publications

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“…In a recent study on aging European men, significant positive associations of E2 and T with CAG repeat length were reported by Huhtaniemi et al (2009). In our study with relatively young men (geometric mean, 29.0 ± 5.9 yrs), a positive, but not significant, linear association between CAG and T levels was also observed, as has been reported in several studies (Crabbe et al, 2007;Mifsud et al, 2001a). The spline regression analysis confirmed that increased E2 levels indeed only occur in men with CAG repeats longer than median length.…”

supporting

confidence: 90%

“…This is unexpected when taking into account the reduced transactivation potential of receptors with short and long repeats as reported by Nenonen 20 et al (2010). However, although not statistically significant, testosterone levels were higher in men with long CAG repeats, which may compensate for reduced receptor activity in these men (Crabbe et al, 2007;Huhtaniemi et al, 2009). Analysis with flexible splines confirmed the u--shaped association of NAG, whereas increased levels of PSA were only apparent in the men with short CAG.…”

mentioning

confidence: 79%

“…Interpretation of these associations is further complicated by the intrinsic complexity of the interaction between AR and its ligands. For example, increased T levels may compensate for the weaker transactivating activity of receptors with short CAG/GGN repeats (Crabbe et al, 2007;Huhtaniemi et al, 2009). In a recent study, Davis--Dao et al (2012) showed an unexpected increased risk of cryptorchidism in cases with short CAG repeats.…”

Section: Ar Is Expressed In Leydig Cells Peritubular Myoid Cells Andmentioning

confidence: 99%

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Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men

Brokken¹,

Rylander²,

Jönsson³

et al. 2013

Molecular and Cellular Endocrinology

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Recently the dogma that there is an inverse linear association between androgen receptor (AR) CAG and GGN polymorphisms and receptor activity has been challenged. We analysed the pattern of association between 21 male reproductive phenotypes and AR CAG/GGN repeat lengths in 557 proven--fertile men.A linear association was only found between sperm DNA fragmentation index (DFI) and CAG length, and between inhibin B and GGN length. Men with longer CAG then the reference (22--24), had higher oestradiol levels, whereas men with shorter CAG stretches had a higher DFI and a higher proportion of Fas--positive germ cells. Subjects with either short or long CAG had increased seminal levels of prostate--specific antigen and neutral α--glucosidase activity. Compared to men with the median GGN length of 23, those with shorter GGN repeats had higher levels of inhibin B, higher proportions of normal and progressive sperm, and a higher fraction of Fas--positive sperm, while men with longer GGN had higher oestradiol levels.These data indicate that at least for some markers of male reproductive function the association with CAG or GGN repeat length is curvilinear.

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supporting

confidence: 90%

mentioning

confidence: 79%

Section: Ar Is Expressed In Leydig Cells Peritubular Myoid Cells Andmentioning

confidence: 99%

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Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men

Brokken¹,

Rylander²,

Jönsson³

et al. 2013

Molecular and Cellular Endocrinology

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“…Whether there exists a threshold at which T levels should be considered "deficient" is still the subject of substantial debate. [14][15][16] Although it is known that comorbidity and health behaviors influence T, 8,17 concurrent changes in health do not appear to account for agerelated declines in T. 8,18 In addition, T levels exhibit substantial random variability over periods of weeks or months. 19,20 The presence or absence of true age-related hypogonadism is therefore difficult to determine.…”

mentioning

confidence: 99%

The Natural History of Symptomatic Androgen Deficiency in Men: Onset, Progression, and Spontaneous Remission

Travison

Shackelton

Araujo

et al. 2008

J American Geriatrics Society

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OBJECTIVES-To describe the onset, progression, and remission of symptomatic androgen deficiency (SAD) using longitudinal data from the Massachusetts Male Aging Study (MMAS).DESIGN-A prospective, population-based study of men living in Boston, Massachusetts. Data were collected in three waves: T1 (1987/89), T2 (1995/97), T3 (2002/04). Onset, progression, and remission were defined in terms of transitions in SAD status from one wave to the next. SETTING-In-person, in-home interviews.PARTICIPANTS-Seven hundred sixty-six community-dwelling men aged 40 to 70 at baseline (T1) contributed data from T1 to T2 and 391 from T2 to T3. MEASUREMENTS-SADwas defined in terms of serum total and free testosterone (T) levels and symptoms associated with low circulating androgens. Total T and sex hormone-binding globulin (SHBG) were measured using radioimmunoassay. Free T was calculated from total T and SHBG measurements. RESULTS-At T2 or T3, the likelihood of SAD was markedly greater for subjects who had exhibited SAD at the previous wave (odds ratio = 3.8, 95% confidence interval = 1.9-7.4), overall 55% of subjects who exhibited SAD experienced remission by the next study wave. The probability of SAD was greater with older age and greater body mass index. Multivariate models demonstrated that the likelihood of remission was at least 50% for most subpopulations.CONCLUSION-Over approximately 15 years of follow-up, SAD did not represent a stable health state. The likelihood of SAD would remit exceeded the likelihood that it Keywords aging; men; androgen; population study Gradual decreases in serum testosterone (T) concentrations are generally believed to accompany male aging. 1-8 Low T levels have been shown to contribute to diabetes mellitus, Address correspondence to: Thomas G. Travison, PhD, New England Research Institutes, 9 Galen St., Watertown, MA 02474. ttravison@neriscience.com. HHS Public AccessAuthor manuscript J Am Geriatr Soc. Author manuscript; available in PMC 2017 August 15. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript low bone and muscle mass, impaired sexual function, and frailty, 9-13 so interventions intended to slow or reverse age-related declines in T have attracted a great deal of attention.Whether there exists a threshold at which T levels should be considered "deficient" is still the subject of substantial debate. [14][15][16] Although it is known that comorbidity and health behaviors influence T, 8,17 concurrent changes in health do not appear to account for agerelated declines in T. 8,18 In addition, T levels exhibit substantial random variability over periods of weeks or months. 19,20 The presence or absence of true age-related hypogonadism is therefore difficult to determine. 21 For these reasons, it has been proposed that a composite measure of T levels and seemingly related symptoms, many of them having to do with mood and self-assessed well-being, may represent a more clinically meaningful assessment of male hormonal status. [22][23][24][25][26][27][28] Implicit in thi...

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“…A reduced number is associated with higher AR transcriptional activity and, therefore, stronger androgen action (Tut et al 1997). Several studies have shown that the number of CAG repeats directly correlates with serum testosterone levels, indicating that the weaker AR activity may indeed be compensated by higher androgen levels (Krithivas et al 1999;Crabbe et al 2007;Huhtaniemi et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Spatial abilities are not related to testosterone levels and variation in the androgen receptor in healthy young men

Kubranská

Lakatošová²,

Schmidtová³

et al. 2014

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Abstract. Androgens modulate brain functions such as cognition, emotions and ability. Several studies have shown a correlation between testosterone levels and mental rotation. The aim of the present study was to confirm the influence of salivary testosterone levels, 2D/4D ratio (such as a putative marker of prenatal testosterone), and sensitivity of androgen receptor on the mental rotation in healthy young men. Seventy-five healthy young men (age, 21.86 year) volunteered in this study. Mental rotation scores of our subjects were assessed using the Vandenberg and Kuse Mental Rotation Test. The 2D/4D finger length ratio as an indicator of prenatal testosterone was used as an average measurement of both hands. Correlation analysis revealed no correlation between salivary testosterone levels and mental rotation. However, we have observed a trend towards a negative correlation. There were no statistically significant results between 2D/4D ratio and mental rotation or between polymorphic three-nucleotide (CAG) repeats and mental rotation tests. Future studies should focus on other genetic determinants of spatial abilities, potentially genes involved in testosterone metabolism.

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Part of the Interindividual Variation in Serum Testosterone Levels in Healthy Men Reflects Differences in Androgen Sensitivity and Feedback Set Point: Contribution of the Androgen Receptor Polyglutamine Tract Polymorphism

Cited by 124 publications

References 32 publications

Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men

Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men

The Natural History of Symptomatic Androgen Deficiency in Men: Onset, Progression, and Spontaneous Remission

Spatial abilities are not related to testosterone levels and variation in the androgen receptor in healthy young men

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