Male Sexual Development Protein Identified

Researchers studying developing mouse embryos have found that a protein called Desert Hedgehog (DHH) is required to induce the differentiation of Leydig cells, the site of synthesis of the male hormone testosterone. This finding was published in the June 1, 2002, issue of Genes & Development.

DHH is one of three mammalian homologs of Hedgehog, which was originally identified in the Drosophila fruit fly, where it regulates body pattern formation. While all three homologs have been found to have important signaling functions during development of the mammalian embryo, the current study established the primary role of DHH in inducing secondary male sex characteristics.

Investigators at Duke University Medical Center (Durham, NC, USA; www.mc.duke.edu) found that DHH and its receptor, Patched 1, were specifically expressed in XY (male) embryos in a temporally and spatially restricted pattern that corresponded to the correct time and place for fetal Leydig cell differentiation. Then, examining males from a strain of mice genetically engineered to lack DHH, they found that the Leydig cell precursors appeared intact, but the mice displayed defects in the differentiation of the precursors into Leydig cells.

While all fetal Leydig cells express the DHH receptor, Patched 1, not all Patched 1-expressing cells become fetal Leydig cells. This finding points to the existence of other signaling pathways that may act in conjunction with DHH/Patched 1 to fine-tune the specification of fetal Leydig cell fate.



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Duke U. Medical Center