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Role of endocytosis in cellular uptake of sex steroids

Item Type:Article
Title:Role of endocytosis in cellular uptake of sex steroids
Creators Name:Hammes, A. and Andreassen, T.K. and Spoelgen, R. and Raila, J. and Huebner, N. and Schulz, H. and Metzger, J. and Schweigert, F.J. and Luppa, P.B. and Nykjaer, A. and Willnow, T.E.
Abstract: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.
Keywords:Androgen Receptors, Androgens, Carrier Proteins, Cell Line, Endocrine System, Endocytosis, Estrogen Receptors, Estrogens, Eukaryotic Cells, Gene Expression Profiling, Gonadal Steroid Hormones, Immunohistochemistry, Knockout Mice, LDL-Receptor Related Protein 2, Pregnancy, Sex Hormone-Binding Globulin, Time Factors, Urogenital Abnormalities, Urogenital System, Animals, Mice
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:122
Number:5
Page Range:751-762
Date:9 September 2005
Official Publication:https://doi.org/10.1016/j.cell.2005.06.032
PubMed:View item in PubMed

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