Physiology of Endocrine System PDF

# Physiology of Endocrine System ## Introduction to the Endocrine System **Mohamed Barhoma** [email protected] **Department of Physiology** **New Valley University** **Egypt** **September 30, 2024** ## Outline 1. **Definitions** 2. **Messengers** 3. **Hypothalamus** **Barhoma (F.V.Ms)** **E...

# Physiology of Endocrine System ## Introduction to the Endocrine System **Mohamed Barhoma** [email protected] **Department of Physiology** **New Valley University** **Egypt** **September 30, 2024** ## Outline 1. **Definitions** 2. **Messengers** 3. **Hypothalamus** **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Definitions * **Endocrine:** Intercellular chemical communication. * **Endocrine system:** Is actually a collection of organs with similar properties. * **Endocrinology:** Is the science which studies hormones, their receptors, their intracellular signaling pathways, and diseased conditions associated with them. * **Endocrine glands:** Are ductless glands that pour their secretion (hormones) directly to the bloodstream which carries these hormones to their site of action (target organ). * **Hormones:** Are chemical substances produced in the body that control and regulate the activity of certain cells or organs. * **Homeostasis:** Is to maintain the internal environment constant. It is crucial for life and so regulation of the body function to maintain this state is important. Generally regulation in mammals' bodies occurs in two methods: * **Neural** * **Hormonal** **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Regulation 1. **Neural Regulation:** Is a fast-acting and occurs within seconds to minutes. It is not a long-lasting mechanism. 2. **Hormonal:** This is with a delayed onset but is long-lasting. ## Common Endocrine Glands 1. **Hypothalamus** 2. **Pituitary gland** (anterior and posterior) 3. **Thyroid gland** 4. **Parathyroid gland** 5. **Adrenal gland** 6. **Pancreases** (islets of Langerhans) 7. **Pineal body** 8. **Thymus** 9. **Gonads** **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Note **Enrichment Knowledges:** * All these glands are important for regulation and normal body function. However, the anterior pituitary, parathyroid, and adrenal cortex are important for life. * Besides these glands, there are other organs that secrete some hormones like: * **Kidney:** secret renin, erythropoietin, calcitriol (active form of vitamin D). * **Heart:** secret ANP (atrial natriuretic factor). **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## General Properties of Hormones 1. They have no direct effect on the gland that secretes them. 2. Some hormones affect all body cells like thyroxine and growth hormone. While others affect only a specific organ (target organ). 3. They trigger certain biochemical changes that continue for sometimes after they disappear from the blood. 4. Some hormones induce other effects besides their main action. For example, insulin stimulates protein synthesis (has an anabolic effect) besides its main hypoglycemic action. 5. Stimuli that stimulate the release of some hormones inhibit the release of other hormones that exert antagonistic effects. For example, hypoglycemia stimulates insulin secretion but suppresses the secretion of the growth hormone and glucagon. 6. Many hormones show cyclic changes in their rate of secretion throughout 24 hours (circadian rhythm). 7. Some hormones are secreted relatively inactive and changed into more active hormones at their target organ. 8. Hormone acts in a very low concentration. 9. Hormones, unlike enzymes, are constantly lost from circulation either by excretion or by their metabolism, i.e. of fading nature. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Local Hormones Apart from these general hormones, there are other types of hormones called local hormones that act near their sites of secretion. Examples include: * Gastrointestinal hormones, e.g. gastrin hormone, CCK. * Various chemical transmitters released by nerve endings. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Forms of Hormones in Blood Most of the hormones are circulating in two forms: 1. **Free form:** This is a very small amount and considers the active form of the hormone. 2. **Bounded form:** This is relatively inactive and found to bind to plasma protein and act as a reservoir for the free form. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## General Function of Hormones 1. Regulate all the metabolic process. 2. Control growth and metamorphosis. 3. Essential for homeostasis. 4. Resistance of stress. 5. Essential for reproduction, particularly sex hormones. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Chemical Nature of Hormones According to chemical nature, hormones may be: * **Lipid-related groups:** As cholesterol derivatives (steroids hormones of the adrenal cortex and sex hormones) and Arachidonic acid derivatives as prostaglandins and leukotrienes. * The steroid hormone is lipid soluble (hydrophobic) so they can easily pass the cell membrane. * **Nitrogen-related groups:** * **Derived from single amino acid:** such as catecholamine's (derived from phenylalanine) and the thyroid gland hormone (derived from tyrosine). * **Chain of peptide (3-200):** such as hypothalamic hormones. * **Protein hormones:** When the peptide chain is attached to other groups like carbohydrates to form glycoprotein hormone (growth hormone, insulin, and corticotrophins). This group is hydrophilic and cannot pass through the cell membrane except with special carrier, so the receptors of these hormones are located at the cell membrane. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Communication of Hormones * **Endocrine communication:** Hormones are secreted into the blood to have an effect on distant target cells (circulatory hormone). * **Paracrine communication:** Endocrine cells secrete hormones into the surrounding extracellular space to the neighboring target cells by diffusion (tissue or local hormone). The local hormones are also called neurotransmitter if they're secreted in the nervous system or chemical mediator when they're secreted in non-nervous system tissue like acetylcholine in the neuromuscular junction (motor end plate). * **Neuro-endocrine communication:** Special nerve cells secrete hormone via one of two paths: * **Directly into the blood:** (norepinephrine from sympathetic nerves). * **Into brain interstitial space:** From which it is drained by portal circulation and transported to target cells (oxytocin, vasopressin from the hypothalamus to the posterior pituitary gland). **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Pheromones These substances (mostly volatile) are secreted by exocrine or endocrine glands to the external environment and carried by air, water, or contact (e.g. licking). ## The Hormone Cycle This includes all hormones' stages, such as: * Synthesis * Storage * Release * Transmission * Trapping * Utilization and action * Inactivation * Excretion **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hormone Synthesis Hormones biosynthesis inside the gland requires raw materials such as: * Tyrosine and iodine in the case of thyroxine hormone. * Cholesterol in the case of steroid hormones. This process also needs energy in the form of ATP and enzymes. The peptide hormones are composed of amino acids. They are synthesized in the ribosome and then transported into the cistern of the rough endoplasmic reticulum and then to the Golgi apparatus. Finally vesicles containing hormones are released from the terminal cistern of the Golgi apparatus. On the other hand, steroid hormones are synthesized with the smooth endoplasmic reticulum. A complex multiple enzyme system is required for the synthesis of steroids. These enzymes are present in the mitochondria and cytoplasm **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Storage and Release * **Storage:** Most of the hormones are after synthesis either inside the cell (pituitary gland and pancreas) or inside the lumen of the follicles as those of the thyroid gland. Hormones inside the cells are stored as granules. During secretion, the granules move to the plasma membrane of the cell where the granule surface membrane fuses with the cell membrane. The membranes are then rupturing, and the granular contents are liberated to the precapillary space. * **Release:** Hormones are released in response to a variety of stimulant agents for the endocrine glands. These may include: * Hormones (as in the thyroid gland, adrenal gland). * Organic substances (glucose in the case of pancreatic islets). * Neural agents (as in the hypothalamus). **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hormone Transporte Hormones are usually transported through a carrier, which is mostly one of the plasma globulins specific for certain hormone. For example: * Thyroxine-binding globulin. * Corticosteroid-binding globulin (transcortin). ## Half-Life Of Hormones This refers to the time required for half of the hormone molecules to become inactivated or removed from circulation. * Smaller peptides, like oxytocin hormone, have a short half-life (2-30 minutes). * Large protein hormones (TSH) have longer half-lives (60 minutes). ## Importance of Carrier * With a carrier, the hormone is inactive, thus it prevents generalization of the hormone effect. * It protects the hormone from enzymes and chemicals. * It facilitates the passage of the hormone through the capillary membrane. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Utilization (Hormone Receptors) Hormonal interaction with target cells begins with reversible binding to highly specific protein receptors (R), forming the H-R complex. * **First messenger:** peptide hormones (hydrophilic) as well as catecholamines present on the cell membrane of target organs (membrane R). * **Steroid hormones (hydrophobic):** These pass through the cell membrane and bind with their specific receptors within the cytoplasm (intracellular R). * **The steroid-receptor complex:** This then migrates to the nucleus where it interacts with specific chromosomal protein. * **Thyroxin (T4):** The major thyroid hormone, is first converted to T3 in the target cell cytoplasm and then interacts directly with chromatin receptors (nuclear R). This is somewhat similar to steroid hormones. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Notes **Receptors Number:** The number of receptors is not fixed. There is a reversible relationship between the receptors number and the hormone concentration. * **Synergistic effect:** Some hormones act together, e.g. estrogen and oxytocin, to increase the number of receptors. * **Antagonistic effect:** Other hormones decrease the number of other hormone receptors e.g. cortisone reduces the insulin receptors. The ability of a hormone to stimulate a cell is regulated by the type and amount of receptors present on the cell membrane. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Down Regulation or Desensitization This phenomenon is observed when the cell is exposed under chronic conditions to relatively high tissue concentrations of a given hormone. This may be due to: * Increase in the number of receptors occupied by hormones * The presence of antibodies that may block the receptor sites * The decrease of synthesis and turnover of the receptors protein by the cell. **N.B.** The number of receptors increases if the level of hormone in the blood is decreased (**up-regulation**). **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hormone Action ### Mechanism of Hormone Action Hormones do their action via binding certain receptors in the target organ. This combination forms a complex (hormone receptor or HR), which leads to the metabolic change in the target, leading to the required response. According to the location of the receptors, there are two types of hormonal action: * **Action that occurs at the level of the intracellular level:** The receptors are located inside the cell and this includes intracytoplasmic receptors (as steroid hormones) and intraneuclear receptors (as those for thyroxine hormone). * **Action at the level of cell membrane:** The receptors are located on the surface of the cell (membrane receptors) and this includes all protein hormones. They do their action via binding to membrane receptors and G protein. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Cell Membrane Receptors A diagram depicts the structure of a cell membrane receptor. The diagram includes: * **GPCR** * **Agonist** * **Ga** * **GDP** * **GTP** * **Beta** * **Gamma** **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Messengers Hormone itself considers the _1st_ messenger and their binding to the receptors leads to the release of the _2nd_ messenger, which may be: * **Cyclic AMP:** Binding of the hormones to their receptors leads to the activation of adenylylcyclase enzyme, which leads to the formation of cyclic AMP. This in turn activates protein kinase A, which catalyzes the phosphorylation of protein, and leads to a conformational change in the target organ cells. Hormones that act via cyclic AMP are calcitonin, glucagon, parathyroid hormone, FSH, LH, TSH, MSH, Gn-RH, and some catecholamines. * **N.B.** Some hormones act by decreasing cyclic AMP, like somatostatin, catecholamines' on alpha2 receptors, and dopamine on D2. * **(IP3): Inositol Triphosphate and Diacylglycerol (DAG):** Binding of these hormones to their receptors results in the activation of phospholipase C, which leads to the cleavage of the phosphatidyl inositol 4,5 piphosphate pip2, forming IP3 and DAG. IP3 diffuses to the endoplasmic reticulum and causes the Ca++ release to the cytoplasm. While DAG leads to the formation of protein kinase C (as protein kinase A in cyclic AMP). This alters the cell function. Hormones that act via this method are norepinephrine on alpha1 receptors and vasopressin in v1 receptor. * **Cyclic GMP:** Binding hormone to receptors lead to activating guanyle cyclase enzyme, which catalyzes the formation of cyclic GMP from GTP. In turn, cyclic GMP activates specific kinase enzymes, which produce the physiological effect. Hormones that act via this method are like atrial natriuretic factors. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Inactivation and Excretion As the hormone gives its cellular response, it's rapidly inactivated and excreted outside the body. * **Peptide and protein hormone:** These are inactivated by peptidase in the liver and kidney. Some hormones are inactivated at the site of their action. In the liver, the protein hormones are degraded by the action of various proteolytic enzymes after inactivation. For example, insulin is inactivated by insulinase enzymes, then it's degraded by various proteolytic enzymes in liver cells. * **Thyroid hormones:** These are usually deiodinized and become inactive. * **Steroid hormones:** These are usually metabolized in liver cells, where they are inactivated. Then they are conjugated to glucuronic acid or sulfate (making them water soluble). These conjugated hormones are rapidly excreted in the urine, and some are excreted through bile to the intestine and then excreted in feces. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Pathway of IP3 and DAG A diagram depicts the pathway of IP3 and DAG. The diagram includes: * **Phospholipac C** * **Cleavage** * **PIP2** * **IP3** * **increase** * **Ca++** * **DAG** * **Activation** * **protein kinase C** **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Inactivation and Excretion Cyclic nucleotides produced by hormone action are rapidly metabolized. c.AMP and cGMP specific phosphodiesterases cleave the cyclic bonds within the cAMP and cGMP to produce inactive 5AMP and 5GMP respectively. Phosphoprotein phosphatase within the cell was dephosphorylate the proteins that were phosphoyrated by cyclic nucleaotid-dependaet protein kinases. Thus the cellular activity is returned to rapidly to the basal level. **Enrichment Knowledges:** Caffeine enhances the stimulatory effect of the cell by inhibition of phosphodiesterase enzymes that convert the cyclic AMP and cGMP to inactive 5-AMP and 5GMP, respectively. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Role Of Calcium In Hormone Action and Secretion * The action of most protein hormones is inhibited in the absence of calcium, even through the ability to increase or decrease cAMP. * Calcium may act as the terminal signal for hormonal action, rather than cAMP. Protein hormones increase the uptake of extracellular calcium, whereas cAMP mobilizes tissue-bound calcium. So hormones increase ionic cytoplasmic calcium. * Secretion of all hormones stored in granules requires calcium. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Pathophysiological Correlates of Hormone Action Hormones deplete its receptors, so deficiency of a certain hormone concentration leads to an increase in its receptors. Conversely, exposure of a cell to a high level of a given hormone results in a decrease in its tissue receptors. **Example:** Thyroxine hormone increases the number of the β-adrenergic receptors in cardiac muscle and vascular tissues. This accounts for the enhancement of sympathetic nervous activity that's usually a symptom of hyperthyroidism. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Some Hormones Receptors Issues * **Myasthenia Gravis:** Myasthenia gravis is an example of an autoimmune disease where antibodies to cholinergic receptors have been developed within the body. These antibodies block the acetylcholine receptors at the neuromuscular junction, which leads to muscular dysfunction and weakness. * **Grave's disease:** In patients with Grave's disease, there's a circulating immunoglobulin that binds to thyrotropin receptors in the thyroid gland, resulting in an excessive increase in T3 and T4. This results in hyperthyroidism. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hypothalamus ### Structure and Endocrine Function of the Hypothalamus * The hypothalamus is the basal part of the diencephalons, lying below the thalamus. * The hypothalamus forms the wall and lower part of the 3rd ventricle of the brain. * It's surrounded cranially by the optic chiasma, caudally by the mammillary body, dorsally by the thalamus, and ventrally by the tuber cinereum. * The lower part of the tuber cinereum is called the median eminence. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hypothalamus A diagram depicts the hypothalamus. The diagram includes: * **Hypothalamus** * **Pituitary** * **Water balance & Stress** * **Hunger** * **Reproduction** * **Thermoregulation** * **Sleep-wake** * **Satiety** * **Optic chiasm** * **Pituitary** **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Anatomical Consideration * **Hypothalamo-hypophysial portal system:** This is a vascular connection between the median eminence and the pituitary. * **Hypothalamic nuclei:** These are neural collections located around the 3rd ventricle. These nuclei are the supraoptic and (SON) and para ventricular nuclei (PNV). These nuclei are composed of cell bodies whose axons extend into the median eminence and then into the neurohypophysis (posterior pituitary). **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Anatomical Consideration * **Magnocellular system:** This refers to the neurosecretory neurons composed of supraoptic and paraventricular neurons, which synthesize oxytocin and vasopressin. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Magnocellular System A diagram depicts the magnocellular system. The diagram includes: * **Paraventricular nucleus** * **Neurosecretory neurons** * **Supraoptic nucleus** * **Hypothalamic-posterior pituitary stalk** * **Anterior pituitary** * **Hypothalamus** * **Vasopressin (ADH)** * **Oxytocin** * **Posterior pituitary** * **Systemic arterial inflow** * **Systemic venous outflow** **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hypothalamic Hormones A diagram depicts the endocrine functions of the hypothalamus and pituitary gland. The diagram includes: * **Posterior Lobe** * **Hypothalamus** * **Neurosecretory cells** * **Hormone** * **Posterior Pituitary** * **Blood vessel** * **Anterior Lobe** * **Neurosecretory cells** * **Blood vessel** * **Releasing hormones from the hypothalamus** * **Endocrine cells of the anterior pituitary** * **Pituitary hormones** * **Anterior pituitary** * **TSH** * **ACTH** * **FSH** * **LH** * **Growth hormone (GH)** * **Prolactin (PRL)** * **Endorphins** * **Oxytoxin** * **ADH** * **Uterine muscles** * **Kidney tubules** * **Mammary glands** * **Thyroid** * **Adrenal cortex** * **Testes or ovaries** * **Entire body** * **Mammary glands** * **Pain receptors in the brain** **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Endocrine Function of Hypothalamus * **Hypothalamic hormones:** It consists of neurosecretory neurons, which secrete neurohormones (hypophysiotropic factors) that regulate adenohypophysial function. * **Connections:** The neurons of the hypothalamus are connected to the rest of the central nervous system by synapses from which it connects other neural elements (cerebral cortex, thalamus, limbic system, spinal cord, and visual centers). * **Information flow:** Information flow from other brain centers is relayed to hypophysiotropic neurons, which then secrete their hypophysiotropic hormones into the portal circulation of the pituitary. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## The Hypophysiotropic Hormones 1. **Thyrotropin-releasing hormone (TRH):** * It's a tripeptide composed of three amino acids (glutamic, histidine, and proline). * It has a potent stimulating action on thyroid-stimulating hormone (TSH). * It also increases the release of PRL in humans, cattle, sheep, and rats. * An increase in the level of circulating TSH or free T3 and T4 blocks the TRH release. * Stress and cold environments enhance TRH secretion. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hypophysiotropic Hormones 2. **Somatostatin (SS) or somatotropin Release-inhibiting hormone (STR-IH) or Growth hormone inhibiting hormone (GHIH):** * This is a polypeptide hormone that inhibits the release of STH or GH and TSH, and to a lesser extend prolactin and ACTH. * This peptide has a widespread effect on the brain, endocrine, and exocrine function of the pancreas and gut function. * Somatostatin lowers blood glucose levels, and this is associated with an inhibition of glucagon and stimulates insulin secretion. * It also inhibits the secretion of renin, parathormone, calcitonin, gastric HCL, and TRH. * It also inhibits the aggregation of the blood platelet. * It's stimulated by somatomedin C from the liver, and acetylcholine from the parasympathetic nerves. * Estrogen blocks its secretion. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hypophysiotropic Hormones 3. **Somatocrinin or Somatotropin releasing hormone (growth hormone releasing hormone (GH-RH):** * It's a polypeptide hormone composed of 44 amino acids, which stimulate STH secretion, and to a lesser extent, prolactin from the pituitary gland. * Somatocrinin is also isolated form human pancreases. * Somatomedin c from liver, GH, morphine, anti-serotonin, and B-adrenergic agonists block its secretion. Its secretion increased by estrogen, serotonin, and stress, and during sleep. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hypophysiotropic Hormones 4. **Gonadotropin Releasing Hormone (GnRH):** * Mammalian GnRH is a decapeptides (10a.a) whose primary structure appears to be similar between mammalian species. * The mechanism by which the GnRH differentially stimulates FSH and LH secretion from folliculotrops and luteotrops at different times during the estrus cycle is unknown. * The GnRH (which is sometimes known as FSH/LH-RH) regulates both the secretion of FSH and LH. * The secretory ratio of FSH and LH differs considerably during the estrus cycle. For example, GnRH mainly stimulates the secretion of LH at the time of ovulation, whereas, at proestrus and estrus (follicular phase), GnRH stimulates the secretion of FSH. * GnRH is controlled by negative feedback with sex hormones. * Increases in its secretion after coitus in cat, camel, and rabbit (induced ovulators) leads to LH surge after 15 minutes, and consequently, ovulation occurs. **Note:** Pheromones could stimulate GnRH release. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hypophysiotropic Hormones 5. **(Corticotropin Releasing Hormone (CRH):** * It's a polypeptide (41a.a) synthesized within the neurons of the hypothalamus. It stimulates the secretion of adrenocorticotrophic hormone (ACTH) from the pituitary gland. * The release of CRH is influenced by stress and circadian light-dark cycles. In diurnal animals, ACTH is high in the early morning and low at night, whereas the reverse is true in nocturnal animals like rats and cats. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hypophysiotropic Hormones 6. **Prolactin Release inhibiting Factor (PIF):** * Prolactin (PRL) secretion from the pars distalis is under an inhibitory control by the hypothalamus. * So hypothalamus lesion or section cause the elevation of prolactin. * Dopamine inhibits PRL secretion from the anterior pituitary. So many authors consider dopamine to be the PIH. * It's the only hypothalamic hormone which is not a peptide hormone (tyrosine). * Dopamine secretion is enhanced by serotonin and inhibited by prolactin, estrogen, tranquilizers, and suckling. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Hypophysiotropic Hormones 7. **Prolactin Releasing factor (PRF):** * There is some experimental evidence for the existence of PRF. TRH is a potent stimulus for PRH. 8. **Melanocyte stimulating Hormone-inhibiting factor (MSH-IF) or Melanostatin:** * Melanocyte-stimulating hormone (MSH) is under an inhibitory control by the hypothalamus. Damage of the hypothalamus results in enhanced MSH secretion. * **N.B.** Posterior pituitary hormones are secreted from the cranial part of the hypothalamus and pass through axons of neurons of paraventricular and supraoptic nuclei to store in the pituitary lobe. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Control of Hypothalamic-Hypophysial Hormone Secretion There are two mechanisms controlling the hypothalamic hypophysial hormones: **A).Role of CNS (neurohormones)** * **Stimuli:** Extrinsic or intrinsic stimuli received through sensory neurons are conducted through neuronal routs to the brain. This information may be inhibitory or stimulatory to hypophysiotropic hormones secretion. * **Conduction:** Conduction of the sensory information involves neuronal elements, and each one releases a neurotransmitter to affect synaptic transmission. * **Neurotransmitters:** These are composed of dopamine, serotonin, epinephrine, and norepinephrine. The axon of the neurons within the brain (extra hypothalamic sites) pass to the hypothalamus where they innervate hypophysiotropic neuron-producing cells. * **Nerve ending:** The nerve ending of these neurons, releases neurotransmitters which may stimulate or inhibit the hypophysiotropin secretion from the peptidergic neuron, and this may inhibit or stimulate pituitary hormones secretion. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Control Of Hypothalamus 1. **Control of the CRH secretion:** * **Stress:** This is a potent stimulus to ACTH secretion. * **Atropine:** This response is diminished by atropine implantation in one or more cholinergic pathways included in the control of ACTH secretion. * **Acetylcholine:** Acetylcholine acts as a stimulatory neurotransmitter for CRH from the hypothalamus. On the other hand, nor epinephrine and epinephrine inhibit stress-induced ACTH secretion. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Control of Hypothalamic Hormones 2. **Control of PIF secretion:** * **Suckling:** During suckling, direct tactile breast stimulation is the normal stimulus to PRL secretion. * **Neuroendocrine reflex:** This neuroendocrine reflex involves the inhibition of dopamine release, which causes the inhibition of PIF, which maintains a tonic inhibition of PRL secretion. * **Neurotransmitters:** Serotonin, GABA, and histamine act as neurotransmitters and play a role in the control of PRL secretion. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Control Of Hypothalamic Hormones 3. **Control of somatotropin releasing hormone secretion** * **Neurotransmitters:** Dopamine, noradrenaline, and serotonin systems are involved in the control of STH secretion but the relationship of these neurotransmitters system to somatostatin or STH releasing hormone is unclear. Gastrin of the GIT and hypothalamic origin are involved in the STH secretion. 4. **Control of the GnRH secretion:** * **Neurotransmitters:** Norepinephrine and dopamine participate in the control of GnRH secretion. The action of dopamine on LH secretion may be dependent on the presence or absence of gonadal steroids. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Control Of Hypothalamic Hormones 5. **Control of TRH secret:** * **Noradrenergic neurons:** These neurons stimulate TSH secretion, apparently by a stimulatory action on TRH-secreting neurons. **b)Feedback Mechanism** * **Hypothalamic hormones:** These cause the release of the pituitary hormones, such as TSH and gonadotropins, into general circulation, where they circulate to their target tissues. * **Target tissues stimulation leads to increased secretion:** This includes target tissue hormones, such as thyroid hormone, adrenal corticosteroids, and Gonadal steroids. * **Circulation to target organs:** These hormones then circulate to their respective target organ to do their action. * **Target organs:** The pituitary gland and hypothalamus themselves are target organs for these hormones. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Mechanisms of Feedback Accordingly, there are three mechanisms of feedback control of hypophysiotropin and hypophysial hormones secretion recognized: * **Long-loop system:** The peripheral target tissue hormones may be feedback through the long-loop system to act at the level of the pituitary, at the hypothalamus, or even higher brain centers. * **Short-loop mechanism:** Hypophysial hormones affect hypothalamic releasing hormone secretion by the short-loop mechanism * **Auto-inhibition or auto feedback inhibition:** The secreted hypophysial hormones may inhibit their own cells by auto-inhibition or auto feedback inhibition. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024** ## Control of Posterior Pituitary Hormones * **Neurohypophysial hormonescontrol:** Neurohypophysial hormones are not controlled by hormonal feedback. They are regulated through reflex mechanisms elicited by other sensory receptors. **Reflex controlling posterior pituitary hormones:** * **Suckling:** Suckling of the breast leads to the secretion of oxytocin from the neurohypophysis. * **Blood volume:** On the other hand, a decrease in blood volume or an increase in electrolytes concentration stimulates vasopressin secretion. **Barhoma (F.V.Ms)** **Endocrine glands** **September 30, 2024**