Continuan~ of vertebrate species and maintenance of mgtabolim~ have an absolute requirement for the glycoprotein hormones of the anterior pituitary gland. It is now firmly accepted that the N-glycans of these and the related placental hormone, ehorionic gonadotropin, have ~ntial if undefined roles in their mechanism of action. However, recent investigations by Weisshaar and his eolleagu~ on the oligosaeeharides of haman luteinizing hormone and chorionie gonadotropin, do not support the generally accepted view of carbohydrates in hormone-rc~ptor interactions and a further concept is propo~xl that invokes negative charges and changes in structured water.Glycoprotein hormone; N-Glycan; Structured waterThe placental glycoprotein hormone, chorionic gonadotropin (CG), is closely related in structure to three hormones that are synthesized and secreted by the anterior pituitary gland in all vertebrates, viz. follicle-stimulating hormone (FSH, follitropin), luteinizing hormone (LH, lutropin) and thyroid stimulating hormone (TSH, thyrotropin). FSH and LH are intrinsic components of the reproductive process, CG like LH stimulates ovary and testis and TSH is an essential regulator of thyroid structure and function.Each hormone consists of two dissimilar subunits and fl, which are highly cross-linked by disulphide bonds, five in each ~ and six in each fl subunit. While the primary structures of the former and their sites of carbohydrate alttachment are virtually the same in all four hormones, the amino acid sequences of the fl elements are unique, in part homologous, and their oligosaceharides differ. The oligosaeeharides in the pituitary glycoprotein hormones are attached through a proximal N-acetylglucosamine residue to the amide nitrogen of asparagine.Chorionic gonadotropin differs in having a C-terminal extension of 30-35 residues in the ,6 subunit that contains four additional oligosaceharide chains Olinked to serine residues in the human hormone. Each subunit is biologically inert, but when associated noncovalently they form the hormonally active heterodimer the specificity of which is conferred by theft component [1].Correspondence address: A. Reawicl~, Department el' Bioehemi~try, University of Auckland, Private Bag 92019, Auckland, New Zealand. Fax: (64) (9) 302 1795.The functions of the N-glycans in the biological actions of these hormones have been inferred from numerous investigations that mainly employed hCG and it is now widely accepted that while the sugar chains are not required for hormone-receptor binding, their presence is essential for activation of the adenylate cyclase system [2-6]. More recent reports provide evidence for subunitand site-specific functions of these oligosaeeharides; those on the ~ subunito primarily at Ash-52, are seemingly more important with respect to hormone assembly, secretion and signal transduction [7][8][9].While crystals of hCG suitable for X-ray diffraction have been obtained [10], no data are yet available. However, one model [3] suggests that the N-glycans of hCG may intera...