Infertility and polysaccharides
Almost all blood and cell surface proteins are not "pure" proteins, but glycoproteins – complex molecules whose properties depend on the composition of not only amino acid chains, but also carbohydrate components (usually polysaccharides). Changing carbohydrates in the composition of glycoproteins is one of the most common ways in nature to modify the properties of proteins, including peptide hormones. Experts believe that different carbohydrate residues determine the ability of proteins to perform various functions or change the nature of their activity depending on changing conditions. However, it has not yet been possible to obtain unambiguous evidence of this hypothesis.
Scientists at the University of Washington, working under the leadership of Professor Jacques Baenziger, have identified a complex of polysaccharides that modify luteinizing hormone and are a link in the feedback mechanism between the pituitary gland, reproductive organs and liver. This mechanism is regularly activated, providing periodic increases in the levels of other reproductive hormones and triggering regular processes, such as the release of an egg by the ovary.
Using genetic methods, the researchers blocked the activity of one of the enzymes that attach carbohydrate residues to luteinizing hormone molecules in mice. This enzyme is only one of a class of its own kind, so its inactivation led to a change in the ratio of carbohydrates modifying luteinizing hormone, and not to their complete absence.
At first, scientists did not notice any features associated with the manipulation. However, it later became clear that, compared with the norm, mice bring about 50% more mice, and their liver removes the altered hormone from the blood much slower. In addition, the females of such mice mature faster, constantly respond to calls for mating and have an altered ovulatory cycle. At the same time, the levels of sex hormones (estrogen and testosterone) are increased in both females and males. It is also interesting that the females of such mice are good mothers – they are less likely than ordinary mice to eat their young.
Based on the results obtained, it can be assumed that some infertility problems in humans are caused by defects in this complex regulatory system – perhaps a change in the profile of carbohydrate residues of a hormone molecule or a receptor for it.
The authors have already received funding to continue their work on the study of the effect of carbohydrate modifications on the activity of reproductive hormones and hope for further success in their work.
Article by Mi Y et al. Ablation of GalNAc-4-sulfotransferase-1 enhances reproduction by altering the carbohydrate structures of luteinizing hormone in mice was published in the Journal of Clinical Investigation on April 21, 2008.