Paracrine hormones

Being a gas, NO is freely diffusible and penetrates cell membranes easily. NO is produced by and acts within the endothelium and platelets but is also a paracrine hormone targeting vascular smooth muscle cells (VSMC) and white blood cells. 

NO fulfills many criteria required to qualify as an intracellular and intercellular messenger. NO is formed with the help of specific enzyme systems activated by extracellular and intracellular signals. NO is synthesized intraceUularly and reaches its effector molecules, which may be localized in the same cell or in neighboring cells, by diffusion. Thus, it has the character of an autocrine or paracrine hormone, as well as an intracellular messenger. 

TEicosanoids are paracrine hormones, substances that act only on cells near the point of hormone synthesis instead of being transported in the blood to act on cells in other tissues or organs. These fatty acid derivatives have a variety of dramatic effects on vertebrate tissues. They are known to be involved in reproductive function in the inflammation, fever, and pain associated with injury or disease in the formation of blood clots and the regulation of blood pressure in gastric acid secretion and in a variety of other processes important in human health or disease. 

Hormones can also be classified by the way they get from the point of their release to their target tissue. Endocrine (from the Greek endon, within, and krinein, to release ) hormones are released into the blood and carried to target cells throughout the body (insulin is an example). Paracrine hormones are released into the extracellular space and diffuse to neighboring target cells (the eicosanoid hormones are of this type). Autocrine hormones are released by and affect the same cell, binding to receptors on the cell surface. 

Arginine vasopressin (AVP) is a potent vasoconstrictor that preferentially reduces renal medullary blood flow through the stimulation of the vasopressin Via receptor (VlaR). Studies have also shown that the vasopressin V2 receptor (V2R) may modulate AVP-mediated vasoconstriction. The transcriptional and translational sites of the VlaR and V2R in micro-dissected intrarenal vascular segments from both the cortex and medulla was studied [154]. The results indicate that VlaR mRNA and proteins are present in the isolated cortical or medullary vasculature, but the V2R mRNA and proteins were not found. This study suggests that the vasoconstrictor action of AVP within the renal medulla is mediated through the VlaR and that the modulatory V2R- mediated vasodilation is probably through the release of paracrine hormones found within the renal interstitial or tubular cells. 

Hormones are classified by the distance within which they act. Autocrine hormones act on the same cell that releases them. An example is interleukin-2. Paracrine hormones act on cells close to the cell that releases them. Examples are prostaglandins and polypeptide growth hormones. Endocrines act on cells at a distance. Examples are the endocrine hormones insulin and epinephrine, which are released into the bloodstream by endocrine glands. (The term endocrine signifies internal secretions directly into the bloodstream, whereas the term exocrine signifies secretions through a duct.) A table of various endocrine hormones is provided in the cited reference. Most hormones consist variously of polypeptides, amino acid derivatives, or steroids. Some examples of sources and functions are as follows. 

Arachidonic acid (20 4n - 6) is one of two major PUFA synthesized by the D6D/D5D pathway (Fig. 4). In many tissues and cell types, 20 4n - 6 is esterified to the sn-2 position of membrane PL, and is used for the eicosanoid-mediated signaling to perform specialized cell functions. Arachidonic acid esterified in PL is a storage form of this fatty acid and is hydrolyzed from the PL by phospholipases prior to enzymatic conversion into eicosanoids (Chapter 13). Eicosanoids are autocrine/paracrine hormones that mediate a variety of localized reactions, such as inflammation, homeostasis, and protection of digestive tract epithelium. D6D deficiency in humans leads to severe food intolerance and growth retardation (J. Nwankwo, 2003). These symptoms are reversed by arachidonic acid supplementation to the diet, which supports the essential role of eicosanoids in the protection of digestive tract mucosa in humans. 

In the brain, NO acts both as a neurotransmitter and as a paracrine hormone. Its functions involve regulation of synaptogenesis, synaptic plasticity, memory formation, cerebral blood flow, olfaction, visual transduction, and neuroendocrine secretion (Schmidt and Walter, 1994). In brain ischemia-reperfusion phenomena -NO has been reported to serve a protective role by inducing vasodilation and reducing neutrophil/platelet adhesion and aggregation, thus leading to increased blood flow, tissue perfusion, and attenuation of the ischemic insult. -NO may also protect the patient from ischemic-induced brain injury by -NO-mediated down-modulation of N-methyl-D-aspartate (NMDA) receptors, thus diminishing NMDA-induced neurotoxicity (Lipton et al., 1993 Choi, 1993 Wink et al., 1993). 

Endothelins are peptide vasoconstrictors formed in and released by endothelial cells in blood vessels. Endothelins are believed to function as autocrine and paracrine hormones in the vasculature. Three different endothelin peptides (ET-1, ET-2, and ET-3) with minor variations in amino acid sequence have been identified in humans. Two receptors have been identified, both of which are G protein-coupled. 

Paracrine hormones, also termed local mediators, peptide hormones involved in biochemical communications which are directed to surrounding cells by diffusion. 

Chalones are extracellular signal molecules that are produced and secreted by differentiated tissue and that act on adjacent cells (target cells) of adjacent tissue (target tissue) which are mitotically active. The chalones act to inhibit mitosis (see Chapter 7). Chalones are a special category of paracrine hormones and are thus not found in a circulating form. There is controversy concerning the nature and existence of chalones. 

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