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Publication : Role of endocytosis in cellular uptake of sex steroids.

First Author  Hammes A Year  2005
Journal  Cell Volume  122
Issue  5 Pages  751-62
PubMed ID  16143106 Mgi Jnum  J:115189
Mgi Id  MGI:3690825 Doi  10.1016/j.cell.2005.06.032
Citation  Hammes A, et al. (2005) Role of endocytosis in cellular uptake of sex steroids. Cell 122(5):751-62
abstractText  Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs.
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