Intracellular metabolism of hCG

After administration of hCG, hormone enters pseudopregnant rat ovarian cells rapidly. Although evidence for small amounts of hCG bound to receptor exists within cells, the major fraction of internalized hCG is free and not receptor bound. The intracellular site of dissociation of hCG from its receptor is unknown. With internalization the hCG molecule is altered so that most of the hormone will no longer bind to concanavalin A. No free hCG alpha or hCG beta was observed for up to 24 hours after internalization. Immunoreactive hCG in cytosol eluted before native highly purified hCG and that altered hCG form may reflect changes in the carbohydrate component of hCG, metabolism of the protein core, or both. Most of the immunoreactive hCG within cytosol remains biologically active for several hours after internalization. The biologic to immunologic (B/I) ratio remained greater than 1.0 for the first six hours after a single injection of hCG. To ascertain whether internalized hCG was predominantly metabolized by lysosomal enzymes in vivo, pseudopregnant rats were pretreated with chloroquine. For the first few hours after hCG stimulation, those animals pretreated with chloroquine attained greater hCG concentrations within the cytosol but membrane bound hCG was lower than that attained for controls. That disparity probably reflected a combination of altered recycling of free hCG receptor in response to chloroquine as well as chloroquine's protecting hormone from lysosomal proteases for a short time after internalization.(ABSTRACT TRUNCATED AT 250 WORDS)