The Molecular Basis of Hormones Endocrine glands and their hormones Introduction Father of Endocrinology Claude Bernard 1849 What is an endocrine gland cid 127 An endocrine gland or tissue is usually defined as a group of cells which synthesizes a chemical that is released into the surrounding medium usually the blood cid 127 Consists of cells with clearly identifiable intracellular secretory machinery cid 127 Contrast with exocrine gland secretes molecules into a duct leading to the exterior of the body cid 127 Classic endocrine glands gonads thyroid adrenals parathyroids pancreatic islets of Langerhans pituitary cid 127 GI tract hormones of particular interest to endocrinologists trying to determine the mechanisms involved in the regulation of food intake hunger and appetite cid 127 CNS the hypothalamus the pineal gland Placenta during pregnancy many hormones are produced by this tissue often in conjunction with the developing fetus feto placental unit cid 127 Other endocrine tissues liver kidneys heart blood adipose tissue lymphoid tissue What is a hormone cid 127 A hormone is that molecule produced by a certain cell or cells the endocrine gland or tissue which is exported out of the cells and it transported to its target cells by a circulating fluid medium the blood Part of the homeostatic response to an altered environment First messengers excludes nutrients excretory products neurotransmitters cid 127 Hormones have specific receptors on the target cells cid 127 Can be released into or enter other circulating fluids such as CSF seminal fluid amniotic fluid lymph cid 127 Most hormones exert their endocrine effect on distant cells but some ex nitric oxide have an effect on nearby adjacent cells paracrine effect and some have an immediate effect on their own cells of production autocrine effect cid 127 Cryptocrine describes the actions of molecules such as hormones which a cell produces and which act within a closed space associated with its cell of production Hormones versus neurotransmitters cid 127 Hormones form a regulatory system which functions to maintain the body s homeostasis in response to perturbing influences stimuli from within as well as from outside the body cid 127 One important part of the brain which plays an essential role in regulating our internal environment is the hypothalamus controls a number of peripheral endocrine glands cid 127 The hypothalamus together with the pituitary is generally called the hypothalamo pituitary axis HPA Some hormones are now known to be produces in the CNS by either neurons or other cells such as glia cid 127 Neurotransmitters and many hormones are essentially released from vesicles into the surrounding fluid by very similar mechanisms involving calcium ions and an expulsion system called exocytosis Similar mechanisms of action essentially involving either ion channels or G protein related receptor Some differences between neurotransmitters and hormones Neurotransmitters Hormones Across synaptic cleft By blood or other fluid Direct to specific neurons or other cells Can be some distance from source cells Milliseconds From seconds up to days cid 127 Hormones can be amines polypeptides proteins or steroids cid 127 Most hormones are either hydrophilic lipophobic polypeptide and protein hormones or hydrophobic lipophilic steroid cid 127 There are other molecules which are very small can have very short lives and which do not readily fall into either of the two main categories these include gaseous molecules such as nitric oxide and carbon monoxide and amines which are amino acid derived hormones share properties of both of the main groups Polypeptide and protein hormones cid 127 Consist of chains of amino acids Polypeptides are chains of 2 100 amino acids while proteins are 100 Transmission Target cells Speed of action Synthesis of Hormones hormones cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 Often synthesized initially as larger precursor molecules called prohormones which are cleaved to form more than one product including the known hormone s cid 127 Organelles ER Golgi complex secretory granules cid 127 The synthesis of a polypeptide hormone generally begins with the formation of an initial larger protein called a pre prohormone moves from its ribosome into the rough ER where it is cleaved into the prohormone then passes into the Golgi complex where it can be modified and or enzymatically cleaved into the biologically active hormone cid 127 Vesicles are an important storage source of the hormone Steroid hormones Synthesized from the same initial precursor cholesterol cid 127 Lipid soluble can pass through the cell membrane Synthesis process involves the activation of specific intracellular enzymes which catalyze chemical conversions such as hydroxylation and aromatization cid 127 Amino acid derived hormones Iodothyronines thyroid gland and cathecholamines adrenal medulla have very specific synthesis pathways Initial precursor molecule is an amino acid and this is enzymatically altered to produce the final bioactive molecule cid 127 Receptors are located on the plasma membranes of their target cells cid 127 The eicosanoids Prostaglandins thromboxanes prostacyclins and leukotrienes Prostaglandins are lipids derived from 20 carbon essential fatty acids called eicosanoids series 1 derived from gamma linolenic acid series 2 from arachidonic acid series 3 from eicosapentanoic acid Series 2 includes the thromboxanes prostacyclins leukotrienes cid 127 Ubiquitous lipids which have physiological and pathological effects within the cells in which they are formed autocrine or on adjacent cells paracrine Precursor substrates are released from the cell membrane phospholipids by the action of specific enzymes The gaseous molecules Nitric oxide and carbon monoxide Very short half lives measured in seconds act only on cells in close proximity to the cells producing them NO was first shown to be produced in living cells in the 1980s numerous physiological effects in maintaining homeostasis synthesized in many body tissues NO is particularly important as a vascular regulator Nitric oxide has a short half life of only a few seconds because it is rapidly inactivated by superoxides ROS The chemical structure of a hormone will play an important part in determining whether or not the hormone is stored prior to its release Storage of hormones Protein and polypeptide hormones the vesicles Amino acid derived hormones Present in the