Impaired development of the reproductive organs in mice lacking megalin, an endocytic receptor for steroid hormones

In the circulation, androgens and estrogens are transported by the carrier sex hormone binding globulin (SHBG). According to current hypotheses, carrier-bound steroid hormones are considered biologically inactive because they are blocked from entering target tissues. Rather, it is the small percentage of free hormones that is believed to enter cells by unspecific diffusion.

Contrary to this “free hormone hypothesis”, Dr. Annette Hammes (laboratory of Prof. Thomas Willnow) and collaborators at the University of Aarhus have now identified an endocytic receptor of the LDL receptor gene family in steroidogenic tissues that mediates the uptake of biologically active androgens and estrogens bound to SHBG. Lack of receptor expression in knockout mice results in impaired development of the male and female reproductive organs, similar to defects observed in animals treated with androgen or estrogen receptor antagonists. ( Cell doi: 10.1016/j.cell.2005.06.032.)

The researchers’ findings uncover the existence of endocytic pathways for protein-bound androgens and estrogens, and the crucial role that they play in urogenital development. More importantly, the identification of pathways for tissue-specific uptake of protein-bound active steroids represents an important paradigm shift in steroid hormone biology.



Pamela Cohen
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