HOW PROTEIN HORMONES REACH THEIR TARGET-CELLS - RECEPTOR-MEDIATED TRANSCYTOSIS OF HCG THROUGH ENDOTHELIAL-CELLS

In many organs the vascular endothelium forms a barrier which impedes the free diffusion of large molecules. The mechanism by which protein hormones are transported through the endothelial cells to reach their target cells is unknown. We have examined the transport of human chori onic gonadotropin (hCG) in rat testicular microvasculature by electron microscopy and by analysing the transfer of radiolabeled hormone and antibodies. Surprisingly, we have observed that the same receptor mole cule which is present in target Leydig cells is also involved in trans cytosis through the endothelial cells. The hormone was internalized by coated pits and vesicles on the luminal side of the endothelium. It w as then localized in the endosomal compartment and subsequently appear ed to be delivered by smooth vesicles into the subendothelial space. M oreover, anti-LH/hCG receptor antibodies were efficiently transported via the same system and delivered into the interstitial space. If gene ralized, these observations may define a new level of modulation of ho rmone action and may be of importance for drug targeting into the nume rous organs which are responsive to the various protein hormones.