Multiple interactions between pituitary hormones and the mannose receptor

The macrophage mannose receptor, which has a well-documented role in the in nate immune system, has an additional function in the clearance of pituitar y hormones. Clearance is mediated by the recognition of sulphated terminal N-acetylgalaadsamine residues (SO4-4GalNAc) on the hormones. Previous studi es with an SO4-4GalNAc-containing neoglycoprotein suggest that the SO4-4Gal NAc-binding site is localized to the N-terminal cysteine-rich domain of the receptor, distinct from the mannose/N-acetylglucosamine/fucose-specific C- type carbohydrate-recognition domains (CRDs). The present study characteriz es the binding of natural pituitary hormone ligands to a soluble portion of the mannose receptor consisting of the whole extracellular domain and to a truncated form containing the eight CRDs but lacking the N-terminal cystei ne-rich domain and the fibronectin type II repeat. Both forms of the recept or show high-affinity saturable binding of lutropin and thyrotropin. Bindin g to the full-length receptor is dependent on pH and ionic strength and is inhibited effectively by SO4-4GalNAc but only partly by mannose. In contras t, binding to the truncated form of the receptor, which is also dependent o n pH and ionic strength, is inhibited by mannose but not by SO4-4GalNAc. Th e results are consistent with the presence of an SO4-4GalNAc-specific bindi ng site in the cysteine-rich domain of the mannose receptor but indicate th at interactions between other sugars on the hormones and the CRDs are also important in hormone binding.