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).