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).