Receptor-mediated transcytosis of follicle-stimulating hormone through the rat testicular microvasculature.
Accumulated data suggest that endothelial cells express specific receptors for several peptide and (glyco)protein hormones that may transport hormones across the cell to be delivered to the interstitial fluid and tissue target cells. Surprisingly, very little information is available on the actual endothelial organelles involved in this cellular process. In the present study the transfer of follicle-stimulating hormone (FSH) through the endothelial barrier of rat testes was examined by analysing the binding and transport of gold-tagged recombinant human (rh)FSH under various conditions using electron microscopy. At 4 degrees C the probe bound specifically to the luminal surface of the endothelial cells without internalization. The use of 125I-rhFSH, which allows precise quantitation of the binding, confirmed the specificity of hormone interaction with the testicular microvasculature. At 37 degrees C the hormone was internalized via coated pits and vesicles into an extensive subluminal tubulo-vesicular compartment and was transported across the endothelium via a system of tubules and vesicles. Moreover, monoclonal antibodies against the FSH receptor ectodomain coupled to colloidal gold followed the same route. In contrast, a non specific, fluid-phase uptake via caveolae was observed for a major plasma protein - rat serum albumin and a fluid-phase tracer - peroxidase. These results suggest that FSH transcytosis across the testicular endothelial barrier is receptor-mediated and involves luminal uptake via coated pits/vesicles, sorting at the level of luminal early endosomes, and transcellular transport through transcytotic tubulo-vesicular organelles. Similar receptor-mediated pathways are likely to be involved in the physiological functioning of a number of other protein and peptide hormones that must translocate specifically from blood to the target cells.
Vu Hai
Mai Thu
MT
Université << René Descartes >> -Paris V, Institut Fédératif de Recherche-95, Laboratoire de microscopie électronique et confocale, 45 rue des Saints Pères, 7500 Paris, France.
Lescop
Pierre
P
Loosfelt
Hugues
H
Ghinea
Nicolae
N
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D018699:Coated Vesicles / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008833:Microcirculation; D008854:Microscopy, Electron; D010477:Perfusion; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011962:Receptors, FSH / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000098:blood supply* / Q000378:metabolism* / Q000648:ultrastructure
D000906:Antibodies; D011962:Receptors, FSH; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP