title: Uteroglobin: a steroid-inducible immunomodulatory protein that founded the Secretoglobin superfamily.
abstract: Blastokinin or uteroglobin (UG) is a steroid-inducible, evolutionarily conserved, secreted protein that has been extensively studied from the standpoint of its structure and molecular biology. However, the physiological function(s) of UG still remains elusive. Isolated from the uterus of rabbits during early pregnancy, UG is the founding member of a growing superfamily of proteins called Secretoglobin (Scgb). Numerous studies demonstrated that UG is a multifunctional protein with antiinflammatory/ immunomodulatory properties. It inhibits soluble phospholipase A(2) activity and binds and perhaps sequesters hydrophobic ligands such as progesterone, retinols, polychlorinated biphenyls, phospholipids, and prostaglandins. In addition to its antiinflammatory activities, UG manifests antichemotactic, antiallergic, antitumorigenic, and embryonic growth-stimulatory activities. The tissue-specific expression of the UG gene is regulated by several steroid hormones, although a nonsteroid hormone, prolactin, further augments its expression in the uterus. The mucosal epithelia of virtually all organs that communicate with the external environment express UG, and it is present in the blood, urine, and other body fluids. Although the physiological functions of this protein are still under investigation, a single nucleotide polymorphism in the UG gene appears to be associated with several inflammatory/autoimmune diseases. Investigations with UG-knockout mice revealed that the absence of this protein leads to phenotypes that suggest its critical homeostatic role(s) against oxidative damage, inflammation, autoimmunity, and cancer. Recent studies on UG-binding proteins (receptors) provide further insight into the multifunctional nature of this protein. Based on its antiinflammatory and antiallergic properties, UG is a potential drug target.
authors.affiliation: Section on Developmental Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institute of Health, Building 10, Bethesda, Maryland 20892-1830, USA. mukherja@exchange.nih.gov
authors.forename: Anil B
authors.initials: AB
authors.lastname: Mukherjee
authors.forename: Zhongjian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Chilton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D014598:Uteroglobin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
chemical_list: D012739:Gonadal Steroid Hormones; D007155:Immunologic Factors; D010455:Peptides; D011994:Recombinant Proteins; D014598:Uteroglobin