1. Role of Endocytosis in Cellular Uptake of Sex Steroids
- Author
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Thomas E. Willnow, Robert Spoelgen, Herbert Schulz, Jochen Metzger, Annette Hammes, Florian J. Schweigert, Peter B. Luppa, Andreas Nykjaer, Norbert Hubner, Thomas K. Andreassen, and Jens Raila
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,medicine.drug_class ,Receptor expression ,Endocytic cycle ,Urogenital System ,Endocrine System ,urologic and male genital diseases ,Endocytosis ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Mice ,Sex hormone-binding globulin ,Pregnancy ,Sex Hormone-Binding Globulin ,Internal medicine ,medicine ,Animals ,Humans ,Gonadal Steroid Hormones ,Receptor ,Mice, Knockout ,biology ,Biochemistry, Genetics and Molecular Biology(all) ,Gene Expression Profiling ,Estrogens ,Sex hormone receptor ,Androgen ,Immunohistochemistry ,Low Density Lipoprotein Receptor-Related Protein-2 ,Eukaryotic Cells ,Endocrinology ,Receptors, Estrogen ,Receptors, Androgen ,Urogenital Abnormalities ,Androgens ,biology.protein ,Female ,Institut für Ernährungswissenschaft ,Carrier Proteins ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
SummaryAndrogens 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.
- Published
- 2005