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Role of Endocytosis in Cellular Uptake of Sex Steroids
- Source :
- Hammes, A, Andreassen, T K, Spoelgen, R, Raila, J, Huebner, N, Schulz, H, Metzger, J, Schweigert, F J, Luppa, P B, Nykjær, A & Willnow, T E 2005, ' Role of endocytosis in cellular uptake of sex steroids ', Cell, vol. 122, pp. 751-762 .
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
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.
- 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
Subjects
Details
- ISSN :
- 00928674
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....eb621e13362bc3e442a1743d5660048c