title: [New achievements in the development and study of the mechanisms of action of the low molecular weight agonists of receptors of the thyroid-stimulating and the luteinizing hormones].
abstract: Pituitary glycoprotein hormones, luteinizing (LH) and thyroid-stimulating (TSH), exert their regulatory effects on cells through the G protein-coupled receptors, specifically binding to their extracellular domain. There is an alternative way of activation of LH and TSH receptors, when low molecular weight organic molecules bind to an allosteric site of the receptors which is localized within their transmembrane channel. Low molecular weight agonists have many advantages over glycoprotein hormones, among them a high efficiency not only in the case of the parenteral but also in the oral administration, low immunogenicity, chemical stability, and a low cost. Unlike pituitary glycoprotein hormones with the agonistic activity, low molecular weight compounds may be either agonists or inverse agonists and neutral antagonists. Recently it was shown that low molecular weight agonists of LH receptor are able to stimulate its mutant forms by restoring the processing of receptor in a cell, and by increasing its sensitivity to LH, which is important for the treatment of reproductive dysfunctions caused by mutations in the LH receptor. This review summarizes the recent achievements that are linked with the development of low molecular weight regulators of TSH and LH receptors and the study of their mechanisms of action. It also presents the author' data concerning the creation of new low molecular weight agonists of LH receptor based on the thienopyrimidine structure, which are effective both in vitro, and in vivo in different ways of administration.
authors.forename: A O
authors.initials: AO
authors.lastname: Shpakov
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D015195:Drug Design; D005786:Gene Expression Regulation; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D011974:Receptors, LH / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011989:Receptors, Thyrotropin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000378:metabolism
chemical_list: D011974:Receptors, LH; D011989:Receptors, Thyrotropin; D054852:Small Molecule Libraries; D007986:Luteinizing Hormone; D013972:Thyrotropin