Mechanisms of humoral regulation of autonomic functions Hormones and Endocrine Secretion Hormones are proteins or lipids which can stimulate target cells even at very low concentrations. They help regulate metabolic processes and homeostasis. Definition endocrine secretion of hormones: A hormone is a molecule such as a protein or a lipid that a cell secretes into interstitial fluid that travels in the blood and acts on target cells. Exocrine secretion releases substances into ducts or a tube that is connected to the outside environment. Endocrine glands control the different metabolic functions: rates of chemical reactions in the cells; transport of substances through the cell membrane; growth; secretions. NATURE OF HORMONS 1. General hormones that are secreted by specific endocrine glands (epinerphine, norepinerphine, ect.); 2. Local hormones that are secreted by different tissues and have specific local effect (secretin, cholecytokinin, ect.). A few general hormones affect all cells of the body (growth hormone, thyroid hormones). Other hormones affect only specific tissues. There tissues have the specific target cell receptors that bind the hormone to initiate their actions (for example, adrenocorticotropin stimulates the adrenal cortex). General hormones – products of endocrine glands Properties of hormones Formed by specialized cells of the endocrine glands (epithelial cells, neuroendocrine cells, myoendocrine cells) Secreted into the blood or other fluids circulating Specificity of action Distant action High activity NOTE:– each hormone has its own onset and duration of action. hormones act in very small concentrations an the blood: a few picograms in one millimiter (1 picogram = 10ˉ¹² g) Properties of local hormones Have a short time of life There are those tissues where formed (or have a paracrine effect - operate on nearby tissues) A basic mechanism of transport is diffusion in a tissue ( in blood does not act) Effects of local hormones Provide rapid self-regulation of tissue processes : local circulation of blood permeability of vessels migratory activity of cells proliferation activity differentiation of cells Main features of humoral regulation Transmitters of information of neural regulation chemicals electric signals, chemicals Ways of passed to information blood and lymphatic vessels, intercellular gaps Method of transmitting Information transfer of chemicals from the blood stream, realization of nervous impulses secretion of neurotransmitters slow, and long duration rapid and immediate by principle "All, who will answer” high addressness, adjusting regulation Speed Addressness nerves Hormone classification By anatomic principle: hormones of hypothalamus hormones of adenohypophysis hormones of neurohypophysis hormones of thyroid gland hormones of parathyroid glands hormones of adrenal cortex hormones of adrenal medulla hormones of sexual glands hormones of pancreas By chemical structure: Steroid hormones mineralocorticoids glucocorticoids female sexual hormones male sexual hormones hormone-active form of vitamin D Amines thyroid hormones catecholamins melatonin Polypeptides and proteins Releasing hormones Vasopressin Oxytocin Anterior pituitary hormones Pancreatic hormones Calcitonin Steroid or steroidlike compounds are lipids: derived from cholesterol. Note the 4 rings. Hormones that contain nitrogen's are the amine, peptide, protein, and glycoprotein hormones. Note the amino group: -NH2 By functional effect: Effector hormones Tropic hormones Releasing hormones By value for the body: Hormones that provide physical, sexual and mental development of the organism: • • • • somatotropic hormone gonadotropic hormones sex hormones neuropeptides Adaptive hormones: • • thyroid hormones glucocorticoids Homeostatic hormones: • • • • aldosterone vasopressin paratyryn insulin Regulation of endocrine glands Neural regulation Neuro-endocrine regulation Endocrine regulation Non-endocrine regulation Metabolites, ions Nervous impulsis Releasing hormones Thropic hormones Adrenal medulla, hypothalamus Anterior lobe of hypophysis Adrenal cortex, thyroid gland, ovaries, testes Parathyroid glands, pancreases STORAGE AND SECRATION OF HORMONES All the protein hormones are formed by the granular endoplasmatic reticulum of the glandular cells (large-molecular preprohormone then is cleaved to smaller prohormone). Final active protein hormone is formed by the Golgi apparatus and compacted into small secretory vesicles. Hypothalamus-pituitary-thyroid axis Hypothalamus-pituitary-gonad axis CONTROL OF HORMONAL SECRETION by negative feedback: Principle of regulation: gland has tendency to over secrete its hormone; target organ performs its function more and more; alteration of function causes a negative effect in the gland to decrease its secretory rate. NOTE: the important factor to be controlled is not the secretory rate of the hormone itself but the degree of the target organ. HORMONAL RECEPTORS Hormones first combine with specific protein receptor on the surface of the cell or inside the cell. The combination of hormone and receptor (H/R) usually initiates a cascade of reactions in the cell. Each stage of reaction in the cascade becomes more powerful than previous stage, so even small initiating hormonal stimulus leads to a large final effect. There are from 2 000 to 100 000 receptors for single hormone in each cell. LOCATION OF THE RECEPTORS: 1. surface of the cell membrane (for protein hormones); 2. in the cell cytoplasm (for steroid hormones); 3. in the cell nucleus (for thyroid hormones) – in direct association with the chromosomes. REGULATION OF NUMBER OF RECEPTORS Receptors may be inactivated and reactivated; receptors may be destroyed and manufactured again. Therefore the responsiveness of the target tissue to the hormone may increase or decrease (up-regulation and down-regulation of receptors). MECHANISM OF HORMONE ACTION 1. Change in membrane permeability opening or closing membrane ion channels (for example, epinerphine). 2. Activation of intracellular enzymes immediately inside the cell membrane with second messenger system (for example, insulin). 3. Activation of genes by building with intracellular receptors: complex of H/R (steroid, thyroid) activates specific portions of DNA that initiates transcription of specific genes to form messenger RNA and appear newly formed proteins; Complex of H/R (growth hormone, perhaps insulin) enhances the translation of messenger RNA in the cytoplasm. Nonsteroid Hormones Amine, peptide, and protein hormones combine with receptors that are located on the surface of the on the target cell membrane. They bind at specific receptor binding sites which activates the receptor. The activity site of the receptor interacts with other membrane proteins that reach across the phospholipid bilayer. Receptor binding can trigger a cascade of biochemical reactions leading to the synthesis of a second messenger such as cyclic AMP. Second Messengers The hormone is the first messenger. Cyclic AMP is a second messenger. Hormone-receptor complex activates a G protein which activates adenylate cyclase which converts ATP to cAMP. cAMP activates protein kinases Protein kinases are enzymes that transfer phosphate groups from ATP to proteins and thereby activates them. These proteins often are regulatory proteins which control metabolism and bring about cellular changes. Phosphodiesterase deactivates cAMP