| Developmental basis of sexually dimorphic digit ratios. | |
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MedLine Citation:
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PMID: 21896736 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Males and females generally have different finger proportions. In males, digit 2 is shorter than digit 4, but in females digit 2 is the same length or longer than digit 4. The second- to fourth-digit (2D:4D) ratio correlates with numerous sexually dimorphic behavioral and physiological conditions. Although correlational studies suggest that digit ratios reflect prenatal exposure to androgen, the developmental mechanism underlying sexually dimorphic digit development remains unknown. Here we report that the 2D:4D ratio in mice is controlled by the balance of androgen to estrogen signaling during a narrow window of digit development. Androgen receptor (AR) and estrogen receptor α (ER-α) activity is higher in digit 4 than in digit 2. Inactivation of AR decreases growth of digit 4, which causes a higher 2D:4D ratio, whereas inactivation of ER-α increases growth of digit 4, which leads to a lower 2D:4D ratio. We also show that addition of androgen has the same effect as inactivation of ER and that addition of estrogen mimics the reduction of AR. Androgen and estrogen differentially regulate the network of genes that controls chondrocyte proliferation, leading to differential growth of digit 4 in males and females. These studies identify previously undescribed molecular dimorphisms between male and female limb buds and provide experimental evidence that the digit ratio is a lifelong signature of prenatal hormonal exposure. Our results also suggest that the 2D:4D ratio can serve as an indicator of disrupted endocrine signaling during early development, which may aid in the identification of fetal origins of adult diseases. |
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Authors:
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Zhengui Zheng; Martin J Cohn |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-06 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-28 Completed Date: 2011-11-21 Revised Date: 2012-03-27 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 16289-94 Citation Subset: IM |
Affiliation:
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Howard Hughes Medical Institute and Department of Molecular Genetics and Microbiology and Department of Biology, University of Florida, Gainesville, FL 32610, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Androgens
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metabolism Animals Estrogens / metabolism Fingers / anatomy & histology* Humans Mice Receptors, Androgen / metabolism Receptors, Estrogen / metabolism Sex Characteristics* Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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R01 ES17099/ES/NIEHS NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Androgens; 0/Estrogens; 0/Receptors, Androgen; 0/Receptors, Estrogen |
| Comments/Corrections | |
Comment In:
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Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16143-4
[PMID:
21930921
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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