Intracellular pathways of electron-opaque gonadotropin-releasing hormone derivatives bound by cultured gonadotropes.

A metabolically stable GnRH agonist (D-Lys6-GnRH) has been coupled to electron-opaque markers (colloidal gold and ferritin) to characterize the intracellular pathway of the releasing hormone bound by pituitary gonadotropes. This approach has the advantage of increasing the resolution of localization to a "circle of uncertainty" about 10- to 20-fold smaller than that which can be obtained by autoradiography. After an initial uniform distribution on the cell surface, the derivatives were taken up individually as well as in small clusters in coated and uncoated membrane invaginations and moved to the lysosomal compartment either directly or after passage through the Golgi apparatus. The results suggest that labeled GnRH or GnRH-receptor complex may be routed to two distinct intracellular compartments: the lysosome and the Golgi cisternae. It is unclear whether each releasing hormone-marker conjugate must be transported through both compartments before degradation.