1/06/2021

Endocrine System

 

Introduction: 

  • The Endocrine System consists of endocrine glands separated from each other by a wide distance.

  • Endocrine glands consist of secretory cells present between a network of capillaries.

  • Secretion of the endocrine gland is called “Hormone”, the hormones secreted diffuse in blood directly and transfer to the target organs.

  • Endocrine glands are also called “Ductless Glands”.

  • It plays a vital role in maintaining homeostasis along with the Nervous system.

  • The branch of science that deals with the study of Endocrine glands is called Endocrinology.

Important Endocrine Glands:

  • Pituitary Gland.

  • Thyroid Gland.

  • Parathyroid Glands.

  • Adrenal Glands.

  • Pineal Gland.

Hormones:

  • The chemicals secreted by Endocrine Glands are called Hormones.

  • Hormones are classified on the basis of the chemical structures as follows,

  • A) Amine Hormones:

    • The hormones that are derived from single amino acids with modified groups in their structures.

    • E.g. Noradrenaline.

    • Melatonin

    • Thyroxin

  • B) Peptide Hormones:

    • The hormones derived from multiple amino acids and contain shorter peptide chains than proteins are called peptide hormones.

    • E.g.

    • ADH (AntiDiuretic Hormone)

    • Oxytocin.

    • Calcitonin

  • C) Protein Hormones: 

    • The hormones derived from multiple amino acids and contain longer peptide chains than peptide hormones are called protein hormones.

    • E.g. Insuline.

    • Growth Hormone.

    • Glucagon.

  • D) Steroid Hormones:

    • Hormones containing steroidal nucleus in their structure are called steroidal hormones.

    • E.g. Testosterone

    • Progesterone.

    • Estrogen

Mechanisms of Hormone Action.

  • The message sent by the endocrine gland through hormone is received in cell by hormone receptor.

  • The receptor then processes the message by initiating various cellular mechanisms to produce target cells' response.

  • The processing is done by one of the either pathways,

    • Pathway involving intracellular hormone receptors.

    • Pathway involving extracellular hormone receptors.

  • Pathway involving intracellular hormone receptors:

    • The lipid soluble hormones like steroidal hormones easily pass the cell membrane.

    • They then attach to the hormone receptor present in the cytoplasm or nucleus of the cell.

    • The hormone receptor complex then attaches to a chromatin and generates a mRNA (messenger RNA) which comes out into cytoplasm.

    • The information written in mRNA is used to synthesize the proteins which in turn produce the target cell’s response.

  • Pathway involving extracellular hormone receptors:

    • Hydrophilic hormones such as Angiotensin II  having lesser lipid solubility cannot pass easily inside a cell.

    • Such hormones attach with a receptor located on a cellular membrane to form a “Hormone - receptor complex”.

    • The formed hormone receptor complex then initiates a cascade of events by forming a second molecule (Second Messenger), resulting in the target cell’s action.

    • Hormone receptor complex works from either of the following pathways,

      • cAMP

      • Phospholipase C.

    • Cyclic Adenosine Mono Amino Phosphate (cAMP) Pathway:

      • The hormone receptor complex activates a cellular component called “G Protein”.

      • The activated G Protein then activates an enzyme “Adenylate cyclase” which causes conversion of ATP (Adenosine Triphosphate) to cAMP.

      •  cAMP activates a type of enzyme called “Protein kinase” which turns cause cascade of phosphorylation events of many proteins activating different enzymes resulting in target cell’s action.

      • The cAMP action is checked by an enzyme “Phosphodiesterase”.

      • E.g. Calcitonin, Glucagon.

    • Phospholipase C pathway:

      • The hormone receptor complex activates a cellular component called “G Protein”.

      • The activated G Protein then activates an enzyme “Phospholipase C” which causes cleavage of a phospholipid from cellular membrane to produce,

        • diacylglycerol (DAG) 

        • inositol triphosphate (IP3)

      • Diacylglycerol activates protein kinase like cAMP while inositol triphosphate causes mobilisation of calcium ions from endoplasmic reticulum, which activates many proteins or enzymes.

      • E.g. Angiotensin II


Pituitary Gland.

Watch the video lecture "Here".

  • Most important gland in the human body, also called “Master Gland”.

  • Pituitary gland along with Hypothalamus forms a “Hypothalamus-Pituitary Complex” which is considered as “Command Center” for the entire endocrine system.

  • Location:

    • It is located below hypothalamus in “hypophyseal fossa” of the sphenoid bone.

    • It is connected with hypothalamus with a string called “Infundibulum”.

  • Structure:

    • Pituitary gland is a bean shaped gland.

    • 1 to 1.5 cm in length.

    • 500 mg in weight.

    • It is divided into two lobes,

      • Anterior Lobe (Adenohypophysis)

      • Posterior Lobe (Neurohypophysis)

  • Anterior Lobe of pituitary gland:

    • Also called “Adenohypophysis”.

    • Secretion of hormones is controlled by hypothalamic hormones.

    • It secretes six hormones as following,

  • 1) Growth Hormone / Somatotropin (GH). (promotes growth).

  • 2) Thyroid Stimulating Hormone / Thyrotropin (TSH). (Stimulates thyroid gland).

  • 3) Adrenocorticotropic Hormone (ACTH). (Stimulates Adrenal Gland).

  • 4) Follicle Stimulating Hormone (FSH). (Stimulates ovaries and testes)

  • 5) Luteinizing Hormone (LH): (Stimulates sex hormone production in gonads).

  • 6) Prolactin: (Stimulates milk production in breasts).

  • Posterior Lobe of pituitary gland:

    • Also called “Neurohypophysis”.

    • It is made up of neural tissues.

    • The hormones from this lobe are actually produced in hypothalamus, it just acts as a storage reservoir.

    • It secretes two hormones as following;

  • 1) Oxytocin (OT): (Contractions of uterus and ejection of milk).

  • 2) AntiDiuretic Hormone  / Vasopressin (ADH): (Increase water reabsorption)

  • Disorders of Pituitary Gland:

  • 1) Pituitary Dwarfism:

    • Characterized by low levels of GH causing impaired growth of the childrens.

  • 2) Gigantism: 

    • Characterized by high levels of GH causing overgrowth of the childrens.

  • 3) Acromegaly:

    • Characterized by high levels of GH causing overgrowth of the feet / face/ limb bones of adults whose growth is stopped.

  • 4) Diabetes insipidus:

    • Characterized by abnormally low levels of ADH causing increased urine formation leading to water loss and hence dehydration

Thyroid Gland:

Watch the video lecture "Here".

  • Location:

    • Present in the neck region just below the larynx. .

  • Structure:

    • Weight is 30 gms.

    • Butterfly shaped.

    • Two lobes, right and left lobe joined by the middle part called “Isthmus”.

    • Each of the thyroid lobes are embedded with parathyroid glands, primarily on their posterior surfaces

    • Thyroid gland is made up of a large no. of follicles called “Thyroid Follicles”.

    • Follicles contain a lumen containing a ground substance called “Colloid” surrounded by cuboidal epithelial cells called “Follicular cells”.

    • Some cells that can not reach the lumen are called “Parafollicular cells / C Cells (Clear Cells)”.

    • Colloid is a sticky liquid that is the center for production of thyroid hormones T3 and T4 from an essential item “Iodine”.

    • C cells secrete a hormone called “Calcitonin” which plays a role in calcium homeostasis.

  • Synthesis Storage & Release of Thyroid Hormones:

  • Steps involved in thyroid hormone synthesis,

    • 1) Thyroglobulin synthesis.

    • 2) Iodide trapping.

    • 3) Oxidation of iodide to iodine.

    • 4) Iodination of thyroglobulin

    • 5) Coupling of two iodinated tyrosine molecules to form T3 / T4.

    • 6) Secretion.

    • Under influence of TSH follicular cells start trapping iodide ions (I-) from blood. (Concn. Of “I” is much higher in cells than in blood).

    • In the lumen of follicular cells the two iodide ions get oxidized to form a molecular iodine molecule “I2” under influence of an enzyme called “Thyroperoxidase”.

    • The formed I2 is then released in the colloid.

    • The follicular cells also release a protein called “Thyroglobulin” in colloid.

    • The colloid Thyroid Peroxidase enzyme links the “Tyrosine” molecule with iodine.

    • Two intermediate are formed

      • Tyrosine attached with one iodine.

      • Tyrosine attached with two iodine molecules.

    • These intermediates fuse with each other to form,

      • Triiodothyronine (T3)

      • Tetraiodothyronine / Thyroxine (T4).

    • The hormones in colloid remain bound with Thyroglobulin.

    • Under influence of TSH the colloid is taken inside the follicular cells by endocytosis.

    • Inside the follicular cell the lysosomal enzymes break down the thyroglobulin and free the hormones T3 and T4.

    • T3 and T4 are lipid soluble diffuse from cell membrane into blood stream.

    • In blood only 1% of thyroid hormones remain unbound.

    • 99% of thyroid hormones are bound to special proteins called “thyroxine-binding globulins (TBGs)”, albumins and other plasma proteins.

    • As plasma concentration of unbound thyroid hormones falls the bounded hormones get released to maintain the ratio.

  • Regulation of thyroid hormone synthesis:

    • In response to decreased blood levels of T3 & T4, Hypothalamus secretes a hormone called “Thyrotropin releasing hormone (TRH)” to the pituitary gland.

    • Pituitary gland in response to TRH releases “Thyroid Stimulating Hormone (TSH) / Thyrotropin”.

    • Thyroid glands under influence of TSH secrete T3 and T4 in blood.

    • Increased levels of T3 & T4 in blood inhibits secretion of TRH & TSH.

  • Functions of Thyroid Hormones:

    • Thyroid hormones attach their receptors present on mitochondria and increase Basal Metabolic Rate (BMR)

    • Also stimulate formation of ATPs in the cell.

    • Stimulates carbohydrate, protein and fat metabolism.

    • Essential for normal brain development.

    • Essential for physical as well as mental growth.

    • Along with sex hormones they are involved in maintaining fertility.

  • Disorders of Thyroid Gland:

  • 1) Cretinism:

    • Also called “Neonatal Hypothyroidism”.

    • It is caused due to low levels of thyroid hormones during birth.

    • It causes severe mental retardness and bone deformities, hearing and speech problems.

  • 2) Myxedema:

    • Caused due to decreased thyroid activity (hypothyroidism).

    • Characterized by facial edema (swelling), lethargy, low body temp., pale skin, muscular weakness, lowered heart rate.

  • 3) Grave’s Disease:

    • Autoimmune disease.

    • Body produces antibodies that mimic the action of TSH.

    • It results in hyperactivity of the Thyroid gland.

    • It is characterized by an increased metabolic rate, excessive body heat and sweating, diarrhea, weight loss, tremors, and increased heart rate.

    • The person's eyes bulge out called “Exophthalmos

  • 4) Goiter:

    • It results due to deficiency of iodine.

    • It is characterized by hypothyroidism.

    • Due to continuous stimulation by TSH the size of thyroid gland increases.


Calcitonin:

  • It is secreted by “C” cells (Parafollicular cells).

  • Released in response to increased blood calcium levels.

  • It decreases blood calcium levels by following mechanisms,

    • Inhibiting the activity of osteoclasts, bone cells that release calcium into the circulation by degrading bone matrix

    • Increasing osteoblastic activity

    • Decreasing calcium absorption in the intestines

    •  Increasing calcium loss in the urine

  • Sometimes used in treatment of “Osteoporosis”.

Parathyroid Glands.

  • Introduction:

    • The parathyroid glands are tiny, round structures usually found embedded in the posterior surface of the thyroid gland.

    • A thick connective tissue separates them from thyroid tissue.

    • Most people have 4 parathyroid glands, but some may have many,

  • Location:

    • They were found embedded in the posterior surface of the thyroid gland.

    • In cases of variation they may present in the neck, chest i.e. in “Thymus” also.

  • Structure:

    • Parathyroid glands contain two types of cells,

      • Chief cells: Secrete “Parathyroid Hormone (PTH)”.

      • Oxyphil cells: Function is unknown yet.

  • Parathyroid Hormone:

    • It is a peptide hormone released in response to low calcium blood levels.

    • It acts in the following ways to correct the lowered blood levels of calcium.

      • It activates Osteoclasts” and mobilises calcium in blood by eroding the bones.

      • It inhibits the “Osteoblasts” and hence prevents calcium deposition in bones.

      • It increases reabsorption of Calcium and Magnesium from kidney tubules.

      • Increases intestinal absorption of calcium.

    • Its secretion is inhibited by increased blood calcium levels : Negative feedback mechanism.

  • Disorders:

    • Hyperparathyroidism:

      • Hyperactivity of parathyroid gland results in high calcium blood levels, causing severe bone deformities and spontaneous fractures.

      • Impairment of body functions.

      • Reduced responsiveness of the nervous system.

    • Hypoparathyroidism:

      • Decreased activity of parathyroid glands results in muscle spasm, convulsions, muscle paralysis.

Adrenal Gland

  • Introduction:

  • Also called “Suprarenal Gland”.

  • Adrenal glands receive one of the highest rates of blood flow in the body.

  • They secrete many essential hormones.

  • Location:

  • Adrenal gland consists of glandular and neuroendocrine tissue adhering to the top of the kidneys by a fibrous capsule.

  • As they are present on top of the kidney they are called “Suprarenal Glands”.

  • Structure:

  • Each adrenal gland is 3-5 cm in height, 2-3 cm in width and about 1 cm thick with a weight of 3.5-5 gm.

  • Each gland consists of two parts.

    • Adrenal cortex – the outer part

    • Adrenal medulla – the inner part

  • Adrenal cortex:

  • The adrenal cortex is divided into three zones

  • Each zone secretes different hormones,

    • Zona glomerulosa – the outer zone secretes mineralocorticoids.

    • Zona fasciculata – the middle zone secrets glucocorticoids.

    • Zona reticularis – the inner zone secrets androgens.

  • Mineralocorticoids:
  • The major mineralocorticoid is aldosterone

  • It maintains water and electrolyte balance in the body.

  • It is secreted in response to 

    • Low Sodium levels.

    • Low blood volume.

    • Low blood pressure.

    • High Potassium levels.

  • Once secreted it,

    • Increases Potassium secretion.

    • Causes Sodium and water retention.

    • Corrects blood volume and blood pressure.

  • Glucocorticoids:
  • Important glucocorticoids are,

    • Cortisol (Hydrocortisone), 

    • Corticosterone and 

    • Cortisone.

  • They have a powerful effect on metabolism.

  • Cortisol is the most active Glucocorticoid, released by the body to handle the stress, hence called “stress hormone”.

  • They possess powerful “Anti-inflammatory action”.

  • In high doses they cause depression of immunity.

  • Androgens:
  • They are steroidal sex hormones produced by Zona reticularis the deepest are of the adrenal cortex.

  • Their amount is very small hence the effect is very minimal.

  • Sex hormones are secreted by gonads on puberty in large quantities.

  • In tissues they get converted to testosterone and estrogen.

  • Adrenal medulla:

  • Adrenal medulla is a part of the sympathetic nervous system and releases hormones namely adrenaline and noradrenaline.

  • These hormones increase activity of heart, blood pressure and metabolism.

  • Disorders of Adrenal Gland:

  • 1) Cushing’s Syndrome:

    • It is caused due to a pituitary tumor causing increased secretion of ACTH which results in high blood levels of cortisol.

    • It is characterized by abnormally high blood glucose levels and accumulation of lipids on the face and neck causing “moon face”.

    • It leads to type II diabetes, weight gain, hair loss, decreased immunity.

  • 2) Addison’s disease:

    • It is a rare disorder.

    • Caused due to hyposecretion of corticosteroids by Adrenal glands.

    • It results in increased potassium and decreased sodium level in blood, low blood pressure, dehydration, weight loss, muscular weakness, decreased cardiac output.


Pineal Gland:

  • Present inferior and slightly posterior to the hypothalamus.

  • Pinealocytes the cells of Pineal gland secrete a hormone called “Melatonin”.

  • Melatonin is responsible for induction of sleep and wakefulness.

  • Secretion of melatonin is dependent on light.

  • Day light causes decreased blood levels of melatonin and induces wakefulness.

  • As light starts to fall after evening blood levels of Melatonin start rising inducing sleep.

  • It helps in maintaining circadian rhythms of the body.

  • It promotes growth and also possesses antioxidant action.

  • Its supplements are used to treat jet lags.

Pancreas

  • The pancreas is a long, slender organ, most of which is located posterior to the bottom half of the stomach.

  • Although pancreas has a main exocrine function some part of it also has endocrine function.

  • Alpha, Beta, Delta and PP cells of Islets of Langerhans of Pancreas have endocrine functionality.

  • Cells and Secretions of the Pancreatic Islets

  • The pancreatic islets each contain four varieties of cells:

  • 1) The alpha cell :

    • Produces the hormone glucagon and makes up approximately 20 percent of each islet. 

    • Glucagon increases blood glucose levels; low blood glucose levels stimulate its release.

  • 2) The beta cell :

    • Produces the hormone Insulin and makes up approximately 75 percent of each islet. 

    • Insulin decreases blood glucose levels; high blood glucose levels stimulate its release.

  • 3) The Delta cell:

    • Produces the hormone Somatostatin and makes up approximately 4 percent of each islet. 

    • Somatostatin is also released by hypothalamus as GHIH (Growth hormone releasing hormone) and gastric mucosa.

    • Pancreatic somatostatin inhibits secretion of insulin and glucagon.

  • 4) The PP cell:

    • Secretes a hormone Pancreatic Polypeptide, and accounts for only 1 percent of the islet.

    • Pancreatic polypeptide hormone regulates exocrine as well as endocrine functions of pancreas.

    • It also regulates appetite and is released during fasting.

  • Disorders of pancreas

  • Diabetes mellitus:

  • It is caused due to deficiency or absence of insulin. 

  • It leads to high blood glucose level and glucose comes in the urine (glycosuria).

  • Symptoms of diabetes mellitus are polyuria (excessive urine production), Polydipsia (excessive thirst) and polyphagia (excessive eating).

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