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Receptors for androgen-binding proteins: internalization and intracellular signalling
C S Porto1, M F Lazari, L C Abreu
1Department of Pharmacology, Escola Paulista Medicina, São Paulo, Brazil.
Summary
Testosterone-estradiol-binding globulin (TeBG) binds to membrane receptors, regulating cellular function. This interaction increases cAMP levels, suggesting a novel signaling pathway beyond steroid transport.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Testosterone-estradiol-binding globulin (TeBG) primarily transports steroid hormones in plasma.
- Previously, TeBG's sole function was thought to be regulating free steroid concentrations.
- Emerging evidence suggests TeBG interacts with specific membrane receptors.
Purpose of the Study:
- To review evidence of androgen-binding proteins interacting with membrane receptors.
- To explore TeBG's role in stimulating cAMP accumulation and cellular uptake.
- To investigate TeBG's signaling mechanism in MCF-7 breast cancer cells.
Main Methods:
- Review of existing scientific literature.
- Experimental studies involving MCF-7 breast cancer cells.
- Measurement of adenylate cyclase activity and cAMP accumulation.
Main Results:
- TeBG binding to MCF-7 cell membranes increases adenylate cyclase activity.
- Unligated TeBG increases intracellular cAMP levels by 30-35%.
- DHT addition after TeBG binding elevates cAMP by over 4-fold, unaffected by antiandrogens.
Conclusions:
- Extracellular sex hormone-binding globulin (SHBG) acts as a cellular function regulator.
- SHBG signaling occurs via a membrane receptor coupled to adenylate cyclase.
- Receptor-mediated endocytosis facilitates TeBG/ABP transfer into tissues.