HUMAN ANATOMY AND PHYSIOLOGY-I (Theory)

Unit I37

Unit II6

Unit III34

Unit IV12

Unit V20

Endocrine system

Endocrine system

The endocrine system is the collection of glands that produce hormones that regulate metabolism, growth and development, tissue function, sexual function, reproduction, sleep, and mood, among other things.

The Endocrine System. The Classification of Hormones

 
A hormone is classically defines as a chemical that is secreted into the blood and acts on a distant target in very low concentrations.

Hormones can be classified according to source or location - heart, liver, pineal gland, hypothalamus, pituitary, thyroid, parathyroid, thymus, pancreas, adrenal cortex, adrenal medulla, kidney, skin, testis, ovaries, adipose tissue, and placenta.

Hormones can be divided into 3 main chemical classes:
  1. Peptide and protein hormones composed of linked amino acids
  2. Steroid hormones are derived from cholesterol
  3. The amine hormones are derivatives of tryptophan or tyrosine
Most hormones are Peptides or Proteins
If a hormone is not a steroid or a amine it is probably a peptide.
A steroid-producing cell would have extensive smooth Endoplasmic Reticulum; a protein-producing cell would have lots of Rough Endoplasmic Reticulum.
Usually made in tissues all over the body unlike steroids that are made only in a few organs
  1. Peptide Hormone Synthesis, Storage and Release
    1. The initial peptide that comes off the ribosome is a large inactive protein called a preprohormone. Preprohormones contain the copies of the peptide hormone and a signal sequence that directs the protein to the lumen of the ER.
    2. Moving through the ER and the Golgi Complex the signal sequence is removed - creating a smaller inactive - Prohormone
    3. Post translation Modification. In the Golgi-apparatus the prohormone is packed in secretory vesicles with proteolytic enzymes that chop the prohormone into active and inactive fragments. 
    4. The secretory vesicle is stored in the cytoplasm until the cell receives a signal for secretion. 
    5. Vesicles move to the cell membrane and release their contents by calcium dependent exocytosis. All the hormones from the prohormone are released together into the extracellular fluid - co-secretion
  2. Post-translation Modification of Prohormones
    1. TRH - has multiple copies of the same hormone 
    2. Proopiomelanocortin - has three active peptides and an inactive fragment
    3. Proinsulin is cleaved in to active insulin and a C-Peptide. The C-peptide is used to measure endogenous secretion of Insulin in diabetics. 
  3. Transport in the Blood and half-life of Peptide hormones
    1. Peptides are water soluble, dissolve easily in the extracellular fluid
    2. Short half life - minutes
  4. Cellular Mechanism of Action of Peptide Hormones
    1. Lipophobic - they are unable to enter the target cell, bind to the target cell membrane receptor. 
    2. Signal transduction system is activated - activation of second messenger systems may activate genes
    3. Most peptide hormones work through cAMPsecond messenger systems. 
    4. Few peptide hormone receptors, such as Insulin, have a tyrosine kinaseactivity or work through other signal transduction pathways
    5. The second messenger system modifies channels and modulate metabolic enzyme or transport proteins.
    6. Effect on target: Modification of existing proteins and induction of new proteins
Steroid Hormones are Derived from Cholesterol
All have a similar structure as they are derived from cholesterol. Steroid hormones are made only in a few organs unlike Peptide hormone synthesis. Three types of steroid hormones are made in the adrenal cortex:
  • Aldosterone - (acts on the Kidney  for Sodium Potassium homeostasis)
  • Cortisol - (acts on many tissues in Stress Response)
  • Androgens - (acts on many tissues in female sex drive) 
The gonads produce sex steroids - estrogen, progesterone, and androgens. Pregnant women placenta is a source of steroid hormones. 
  1. Steroid Hormone Synthesis and Release
    1. Cells that secrete steroid hormones have large amount of smooth Endoplasmic Reticulum, the organelle in which steroids are synthesised.
    2. Steroids are lipophillic and diffuse across membranes, both out of the parent cell and into the target cell.
    3. This means that steroid producing cells cant store hormones in secretory vesicles - they synthesize hormone on demand
    4. The steroid hormone moves out of the cell by simple diffusion
  2. Transport in the Blood and half-life of Steroid Hormones
    1. Bound to carrier proteins: Steroids are not water soluble and need to be transported using a transport protein like albumin. Corticosteroid binding globulin is specific carrier protein for cortisol
    2. The binding to carrier proteins protects the hormone from enzymatic degeneration and results in an extended half life. Cortisol, produced by the adrenal cortex, t1/2 = 60-90 minutes. This is a long half life. Aldosterone has a short half life for a steroid hormone, about 20 minutes - suggesting that it not bound to plasma proteins as much as other steroids. 
    3. The lipophobic protein in the carrier-steroid complex cant diffuse into the target cell, so the steroid remains inactive. Only unbound steroid hormone can diffuse to the target cell. 
    4. Thank God that only a small amount of steroid is needed to produce a response. The Kd - dissociation constant - obeys the law of mass action.
  3. Cellular Mechanism of Action of Steroid Hormones
    1. Location of receptor: cytoplasm or nucleus; some have membrane receptors also. 
    2. Response to receptor ligand binding: Activation of genes for the transcription and translation. Usually acts as a transcription factor that activates or repressing one or more genes - the genomic effect. 
    3. There is a lag between hormonal binding and the first new protein manufactured - the lag can be as much as 90 minutes. Consequently, steroid hormones do not mediate reflex pathways that require rapid responses.
    4. Induction of new protein synthesis. 
    5. There are also membrane receptors for pathways of estrogens and aldosterone - that linked to signal transduction pathways - these receptors initiate rapid non-genomic responses.
Amine Hormones are derived from One of Two Amino Acids - derivatives of tryptophan or tyrosine

The amine hormones are small molecules created from tryptophan or tyrosine.
The amine melatonin is derived from tryptophan, all the other amines hormones, catacholamines (dopamine, norepinepharine and epinepharine) and thyroid hormones are derived from tyrosine.
The catacholamines have one thyrosine and the tyroid molecules have two thyrosine molecules plus iodine.
The catacholamines are neurohormones that bind to cell membrane receptors as peptide hormones do.
The tyroid hormones, produced in the tyroid, act like steroid hormones, with intracellular receptors that activate genes.

Mechanism of hormone action

Each hormone has receptors that are found on the cell membrane of the target organ. Once the hormone bind to its designated receptor, a series of actions are initiated to release secondary messengers inside the cell. These secondary messengers are responsible for relaying information to the nucleus or other organelles. Based on their structure, receptors are of different types:

Internal receptors– they can be either nuclear or cytoplasmic. Nuclear receptors are found on the nuclear membrane while the cytoplasmic receptors are found in the cytoplasm of the cell. These receptors are for the steroid hormones.

External receptors– These are the transmembrane receptors which are embedded in the lipid layer of the cell membrane. These receptors are for the protein ones.

The mechanism of action hormone can be of two types: First, where the receptors are fixed and the second, where the receptors are mobile.

Fixed Receptor Mechanism

 (Image Source: biology-spaces.info)

This mechanism of action hormone is seen in the protein hormones such as Adrenaline, insulin, ADH, TSH etc. As mentioned earlier, since they are water soluble, they cannot pass through the cell membrane as it is made up of a lipid layer. So, they bind to their extracellular receptors present on the membrane.

Once the protein hormone binds to the receptor, a series of reactions occur beginning with the production of adenyl cyclase enzyme. This enzyme leads to the production of cyclic AMP or cAMP which is the secondary messenger. This cAMP can now enter the cell and cause the effect it was meant to bring about.

Mobile Receptor Mechanism

 

 

This kind of mechanism is seen in the steroid hormone that is insoluble in water. They are made up of fats and therefore can freely cause the lipid layer of the cell membrane. Their receptors are intracellular and not extracellular like those for the protein ones. The intracellular receptors can be floating in the cytoplasm, on the nuclear membrane or inside the nucleus. For this reason, their receptors are known as mobile receptors.

pituitary gland

 

The pituitary gland is a part of your endocrine system. Its main function is to secrete hormones into your bloodstream. These hormones can affect other organs and glands, especially your:

The pituitary gland is sometimes called the master gland because it’s involved in so many processes.

Pituitary gland anatomy and function

The pituitary gland is small and oval-shaped. It’s located behind your nose, near the underside of your brain. It’s attached to the hypothalamus by a stalklike structure.

The hypothalamus is a small area of your brain. It’s very important in controlling the balance of your bodily functions. It controls the release of hormones from the pituitary gland.

The pituitary gland can be divided into two different parts: the anterior and posterior lobes.

Anterior lobe

The anterior lobe of your pituitary gland is made up of several different types of cells that produce and release different types of hormones, including:

  • Growth hormone. Growth hormone regulates growth and physical development. It can stimulate growth in almost all of your tissues. Its primary targets are bones and muscles.
  • Thyroid-stimulating hormone. This hormone activates your thyroid to release thyroid hormones. Your thyroid gland and the hormones it produces are crucial for metabolism.
  • Adrenocorticotropic hormone. This hormone stimulates your adrenal glands to produce cortisol and other hormones.
  • Follicle-stimulating hormone. Follicle-stimulating hormone is involved with estrogen secretion and the growth of egg cells in women. It’s also important for sperm cell production in men.
  • Luteinizing hormone. Luteinizing hormone is involved in the production of estrogen in women and testosterone in men.
  • Prolactin. Prolactin helps women who are breastfeeding produce milk.
  • Endorphins. Endorphins have pain-relieving properties and are thought to be connected to the “pleasure centers” of the brain.
  • Enkephalins. Enkephalins are closely related to endorphins and have similar pain-relieving effects.
  • Beta-melanocyte-stimulating hormone. This hormone helps to stimulate increased pigmentation of your skin in response to exposure to ultraviolet radiation.

Posterior lobe

The posterior lobe of the pituitary gland also secretes hormones. These hormones are usually produced in your hypothalamus and stored in the posterior lobe until they’re released.

Hormones stored in the posterior lobe include:

  • Vasopressin. This is also called antidiuretic hormone. It helps your body conserve water and prevent dehydration.
  • Oxytocin. This hormone stimulates the release of breast milk. It also stimulates contractions of the uterus during labor.

Thyroid gland

The thyroid gland is a butterfly-shaped organ located in the base of your neck. It releases hormones that control metabolism—the way your body uses energy. The thyroid's hormones regulate vital body functions, including:

  • Breathing
  • Heart rate
  • Central and peripheral nervous systems
  • Body weight
  • Muscle strength
  • Menstrual cycles›
  • Body temperature
  • Cholesterol levels
  • The thyroid gland is about 2-inches long and lies in front of your throat below the prominence of thyroid cartilage sometimes called the Adam's apple.
  • The thyroid has two sides called lobes that lie on either side of your windpipe, and is usually connected by a strip of thyroid tissue known as an isthmus. Some people do not have an isthmus, and instead have two separate thyroid lobes

How the Thyroid Gland Works

The thyroid is part of the endocrine system, which is made up of glands that produce, store, and release hormones into the bloodstream so the hormones can reach the body's cells. The thyroid gland uses iodine from the foods you eat to make two main hormones:

  • Tri-iodothyronine (T3)
  • Thyroxine (T4)

It is important that T3 and T4 levels are neither too high nor too low. Two glands in the brain—the hypothalamus and the pituitary communicate to maintain T3 and T4 balance.

The hypothalamus produces TSH Releasing Hormone (TRH) that signals the pituitary to tell the thyroid gland to produce more or less of T3 and T4 by either increasing or decreasing the release of a hormone called thyroid stimulating hormone (TSH).

  • When T3 and T4 levels are low in the blood, the pituitary gland releases more TSH to tell the thyroid gland to produce more thyroid hormones.
  • If T3 and T4 levels are high, the pituitary gland releases less TSH to the thyroid gland to slow production of these hormones.

T3 and T4 travel in your bloodstream to reach almost every cell in the body. The hormones regulate the speed with which the cells/metabolism work. For example, T3 and T4 regulate your heart rate and how fast your intestines process food. So if T3 and T4 levels are low, your heart rate may be slower than normal, and you may have constipation/weight gain. If T3 and T4 levels are high, you may have a rapid heart rate and diarrhea/weight loss.

Listed below are other symptoms of too much T3 and T4 in your body (hyperthyroidism):

  • Anxiety
  • Irritability or moodiness
  • Nervousness, hyperactivity
  • Sweating or sensitivity to high temperatures
  • Hand trembling (shaking)
  • Hair loss
  • Missed or light menstrual periods

The following are other symptoms that may indicate too little T3 and T4 in your body (hypothyroidism):

  • Trouble sleeping
  • Tiredness and fatigue
  • Difficulty concentrating
  • Dry skin and hair
  • Depression
  • Sensitivity to cold temperature
  • Frequent, heavy periods
  • Joint and muscle pain

Parathyroid glands

Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods that produce parathyroid hormone. Humans usually have four parathyroid glands, variably located on the back of the thyroid gland. Parathyroid hormone and calcitonin (one of the hormones made by the thyroid gland) have key roles in regulating the amount of calcium in the blood and within the bones.

Parathyroid glands share a similar blood supply, venous drainage, and lymphatic drainage to the thyroid glands. Parathyroid glands are derived from the epithelial lining of the third and fourth pharyngeal pouches, with the superior glands arising from the fourth pouch, and the inferior glands arising from the higher third pouch. The relative position of the inferior and superior glands, which are named according to their final location, changes because of the migration of embryological tissues.

Hyperparathyroidism and hypoparathyroidism, characterized by alterations in the blood calcium levels and bone metabolism, are states of either surplus or deficient parathyroid function

Structure

  • The parathyroid glands are two pairs of glands usually positioned behind the left and right lobes of the thyroid.
  • Each gland is a yellowish-brown flat ovoid that resembles a lentil seed, usually about 6 mm long and 3 to 4 mm wide, and 1 to 2 mm anteroposteriorly. 
  • There are typically four parathyroid glands. The two parathyroid glands on each side which are positioned higher are called the superior parathyroid glands, while the lower two are called the inferior parathyroid glands.
  • Healthy parathyroid glands generally weigh about 30 mg in men and 35 mg in women. These glands are not visible or able to be felt during examination of the neck.
  • Each parathyroid vein drains into the superior, middle and inferior thyroid veins. The superior and middle thyroid veins drain into the internal jugular vein, and the inferior thyroid vein drains into the brachiocephalic vein.

Function

The major function of the parathyroid glands is to maintain the body's calcium and phosphate levels within a very narrow range, so that the nervous and muscular systems can function properly. The parathyroid glands do this by secreting parathyroid hormone (PTH).

Parathyroid hormone (also known as parathormone) is a small protein that takes part in the control of calcium and phosphate homeostasis, as well as bone physiology. Parathyroid hormone has effects antagonistic to those of calcitonin.

  • Calcium. PTH increases blood calcium levels by directly stimulating osteoclasts and thereby indirectly stimulating osteoblasts (through RANK/RANKL mechanism) to break down bone and release calcium. PTH increases gastrointestinal calcium absorption by activating vitamin D, and promotes calcium conservation (reabsorption) by the kidneys.
  • Phosphate. PTH is the major regulator of serum phosphate concentrations via actions on the kidney. It is an inhibitor of proximal tubular reabsorption of phosphorus. Through activation of vitamin D the absorption (intestinal) of Phosphate is increased.

 

 

 

 

 

 

 

 

 

 

 

 

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