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 chorionic 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 molecule which is present in target Leydig cells is also involved in transcytosis through the endothelial cells. The hormone was internalized by coated pits and vesicles on the luminal side of the endothelium. It was then localized in the endosomal compartment and subsequently appeared to be delivered by smooth vesicles into the subendothelial space. Moreover, anti-LH/hCG receptor antibodies were efficiently transported via the same system and delivered into the interstitial space. If generalized, these observations may define a new level of modulation of hormone action and may be of importance for drug targeting into the numerous organs which are responsive to the various protein hormones.