2nd to 4th digit ratios, fetal testosterone and estradiol
Introduction
The Homeobox genes Hox a and d control (a) the differentiation of the urinogenital system, and may therefore indirectly influence the prenatal production of testicular androgen and (b) the development of the digits [1], [2]. This observation has led to the suggestion that patterns of digit formation may relate to gonad function [3]. One likely candidate for such a link is the ratio between the length of the 2nd (the “index” finger) and 4th (the “ring” finger) digit (2D:4D). The 2D:4D ratio is a sexually dimorphic trait which is lower in men than women [3], [4], relative digit length is established as early as the 14th week [5], and the sex difference appears by two years and perhaps before birth [3].
2D:4D is associated with measures of size at birth in males [6], sperm counts [3], family size [7], age at breast cancer presentation [8] and age at myocardial infarction [9]. It is therefore important to understand the factors which lead to 2D:4D formation. There is indirect evidence that the sex difference in 2D:4D is causally related to relative concentrations of testosterone and oestrogen. Thus, (a) the waist/hip ratio of mothers, a positive correlate of testosterone and a negative correlate of estradiol, is negatively related to the 2D:4D ratio of their male and female children [10]; (b) some behavioural traits with an excess of males have been shown to be associated with low values of 2D:4D, e.g. left hand preference [11], good visual-spatial ability [12], autism and Asperger's syndrome [13]; (c) males and females with congenital adrenal hyperplasia, a trait associated with high prenatal testosterone, have low values of 2D:4D compared to controls [14], [15]; and (c) traits which show an excess of females, e.g. high verbal fluency [16] and high levels of emotional behaviour [17], are associated with high 2D:4D. However, these and similar observations may result from interactions between 2D:4D and sex-related factors other than prenatal androgen and estradiol. The purpose of this work was to examine the association between 2D:4D and relative concentrations of fetal testosterone (FT) and estradiol (FE).
Section snippets
Subjects and methods
FT and FE may be obtained from amniocentesis [18]. This test is offered to mothers in the second trimester of their pregnancy when there is an elevated risk of a fetus with a chromosomal abnormality. The mothers in this study had undergone routine amniocentesis in the Cambridge area in 1996 and 1997, and had all given birth to healthy singleton infants. The protocol was agreed by the local Ethics Committees and informed consent was obtained from the mothers.
The amniotic fluid was analysed in
Results
There were 33 children, 18 males and 15 females, in the sample. Means for hormonal concentrations were FT=0.72±0.46 nmol/l, FE=1013±379.05 pmol/l and FT/FE ratio 0.001±0.001. Male children had significantly higher levels of FT than females (males 0.91±0.31, females 0.52±0.53, t=2.62, p=0.01). There were no significant differences in FE between the sexes (males 979.77±372.30, females 1058.73±407.02, t=0.57, p=0.57). FT/FE ratios showed significantly higher values for males compared to females
Discussion
We have found that low 2D:4D ratios are associated with high FT in relation to FE levels, and high values of 2D:4D with low FT and high FE. The relationship is likely to reflect testosterone produced by the fetal gonads and adrenals as the fetus is isolated from maternal androgen by its conversion to estradiol within the placenta by the enzyme aromatase [20]. It may be noteworthy that all relationships between 2D:4D and fetal sex steroids were stronger in the right hand than the left. Traits
Acknowledgements
This work was submitted in part fulfillment of the degree of PhD by SL to the University of Cambridge. SBC and SL were supported by the MRC during the period of this work. RK was supported by an Overseas Research Studentship, Cambridge Overseas Trust, and Gonville and Caius College. We are grateful to the Gatsby Foundation for supporting the costs of biochemistry analysis.
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