In vertebrates, endocrine glands are specialized organs that secrete hormones into the endocrine signaling system. Hormone secretion occurs in response to specific biochemical signals and is often subject to negative feedback regulation. For instance, high blood sugar (serum glucose concentration) promotes insulin synthesis. Insulin then acts to reduce glucose levels and maintain homeostasis, leading to reduced insulin levels. Upon secretion water soluble hormones are readily transported through the circulatory system. Lipid-soluble hormones must bond to carrier plasma glycoproteins (e.g., thyroxine-binding globulin (TBG)) to form ligand-protein complexes. Some hormones are completely active when released into the bloodstream (as is the case for insulin and growth hormones), while others are prohormones that must be activated in specific cells through a series of activation steps that are commonly highly regulated. The endocrine system secretes hormones directly into the bloodstream, typically via fenestrated capillaries, whereas the exocrine system secretes its hormones indirectly using ducts. Hormones with paracrine function diffuse through the interstitial spaces to nearby target tissue.