Introduction To Endocrinology

Question 1

Nervous system

Answer 1

• Rapid control system
• Rapid response
• Effect lasts briefer
• Acts on specific targets

Question 2

Endocrine system

Answer 2

Slower control system

• slower response
• effect lasts longer
• broader influence (acts also on distant organs)

Is a chemical messenger system, circulatory system= mean of propagation

Question 3

Endocrine system: functions

Answer 3

• Metabolism
• Growth= longitudinal and development of mature tissues (GH VS dwarfism)
• Development
• Water and electrolyte balance
• Reproduction (Sex hormones VS lack of sexual development)
• Behavior

Thyroxine and triiodothyronine VS sluggish reactions body
Insulin VS lack of energy taken up from carbohydrates

Question 4

Neurotransmitters

Answer 4

Are released by the axon terminals of neurons into the synaptic junctions and act locally to control nerve cell functions

Extra: It is a type of chemical messenger which transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron (nerve cell) to another “target” neuron, muscle cell, or gland cell.

Examples: acetylcholine, GABA, dopamine, serotonin, glutamate, norepinephrine

Question 5

Endocrine

Answer 5

Are released by glands or specialized cells into the circulating blood. Influence the function of target cells at another location in the body

Question 6

Neuroendocrine

Answer 6

Are released by neurons into the circulating blood and influence the function of target cells at another location in the body

Neuroendocrine cells are cells that receive neuronal input (neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release message molecules (hormones) into the blood.

Examples: somatostatin, vasopressin, corticotropin- , growth hormone and thyrotropin- releasing hormones

Question 7

Paracrine

Answer 7

Are released by cells into the extracellular fluid and affect neighboring cells which can be of the same or of a different cell types

Question 8

Autocrine

Answer 8

are secreted by cells into the extracellular fluid and act on the same cell that secretes them

Question 9

Cytokines

Answer 9

Are peptides secreted by cells into the extracellular fluid
Can function as paracrines, autocrines or endocrine hormones

Ex: interleukins secreted often by CD4 T lymphocytes
Adipokines secreted by adipose tissue

Question 10

Endocrine glands

Answer 10

• Ductless
• Products are secreted into the blood
• Can reach distant tissues

Examples: Langerhans cells in the pancreas that secrete insulin and glucagon and somatostatin

Question 11

Examples of peptide and protein hormones (1), steroid hormones (2) and hormones derivative of the amino acid tyrosine (3)

Answer 11

1.Anterior and posterior pituitary gland
Pancreas= insulin and glucagon
Parathyroid gland = parathyroid hormone

2.Adrenal cortex= cortisol and aldosterone
Ovaries= estrogen and progesterone
Testis= testosterone

3. Thyroid= thyroxine and triiodothyronine
   Adrenal medullas= epinephrine and norepinephrine

Question 12

Peptide and protein hormones

Answer 12

Peptide hormones <100 amino acids
Proteins >= 100 amino acids
Water soluble

Synthesized in the rough end of the ER as larger proteins which are not active (preprohormones)
Then cleaved into the ER to form pro hormones
Transferred to the Golgi apparatus where packed into vesicles (in which enzymes cleave them into a biologically active and and inactive fragment)
Secretion of the contents of the vesicles through exocytosis

Stimulus : increase in cytosolic calcium concentration caused by depolarization of the plasma membrane
Stimulation of an endocrine cell surface receptor—> increased cAMP and activation of protein kinases —> secretion of hormone

Question 13

Steroid hormones

Answer 13

Structure similar to cholesterol
Formed by three cyclohexyl rings and one cyclopentyl ring
Lipid soluble - diffuse through the plasma membrane

Steroid producing endocrine cells have few storage for steroid hormones
BUT large storage of cholesterol esters in cytoplasm vacuoles which after a stimulus are mobilized for steroid synthesis

Cholesterol

• comes from plasma
• de novo synthesis

Question 14

Amine hormones derived from tyrosine

Answer 14

Both synthesized by enzymes in the cytoplasmic compartments of glandular cells

Thyroid hormones: synthesized and stored in the thyroid gland, incorporated into thyroglobulin, stored in the thyroid follicles.
When amines are split from thyroglobulin and free hormones are released in the cytoplasm—> hormones enter in the blood. Most of the thyroid hormones combine with plasma proteins especially thyroxine-binding globulin.

Adrenal medullary hormones= epinephrine and norepinephrine
They are taken up into preformed vesicles and stored until secreted.
Released by exocytosis
Can exist in plasma in free form or in conjugation to other substances

Question 15

Negative feedback

Answer 15

After a stimulus causes release of a hormone, conditions or products resulting from the action of the hormone tend to suppress its further release. The controlled variable is sometimes not the secretory rate of the hormone itself but the degree of activity of the target tissue.
Feedback regulation can occur at all levels, including gene transcription and translation involved in synthesis of hormones, steps involved in processing and releasing stored hormones

Question 16

Negative feedback: examples

Insulin and glucose

Answer 16

Eat—> stimulus: rising blood glucose level—> high blood glucose level is detected by insulin- secreting cells of pancreas—>pancreas secretes insulin—> liver cells take up glucose and store it as glycogen and also most body cells take up more glucose—> glucose levels in the blood decrease—> insulin release stops—> return to homeostatic blood glucose level

Question 17

Negative feedback example: TSH and TRH

Answer 17

TRH is secreted by hypothalamus—> it is detected by some specific cells of the anterior pituitary—> stimulated by TRH they produce TSH—> TSH is detected by TSH receptors in the thyroid gland—> production of thyroid hormones T3 and T4.
Thyroid hormones exert a negative feedback effect on the hypothalamus and on the pituitary—> reduce production of TSH and TRH (VS hyperthyroidism = The term hyperthyroidism refers to any condition in which there is too much thyroid hormone produced in the body. In other words, the thyroid gland is overactive)

Question 18

Positive feedback

Answer 18

The biological action of the hormone causes additional secretion of the hormone

Question 19

Positive feedback: examples

Uterus dilation

Answer 19

Baby’s growth takes up all the space in the uterus—> stretch receptors in the uterus detect the dilation—> brain signals for release of oxytocin—> contractions of uterine muscles (they get stronger until the baby is delivered)

Question 20

Positive feedback: examples

Milk release

Answer 20

Stimulus: baby suckles at nipples—> suckling sends impulses to the hypothalamus—> hypothalamus signals posterior pituitary to release oxytocin—> stimulates milk ejection—> milk is released and the baby continues to feed.

Question 21

Cyclical variations

Answer 21

Superimposed on the negative and positive feedback are periodic variations in hormone release that are influenced by seasonal changes, stages of development and aging, daily cycle and sleep.
In many cases these changes are due to changes in neural pathways which control hormone release

Question 22

Pulsatility

Answer 22

Pulsatile secretion is a biochemical phenomenon in which a chemical, such as a hormone, is secreted in a burst-like or episodic manner rather than constantly. Examples of hormones that are secreted pulsatilely include gonadotropin-releasing hormone (GnRH) and growth hormone (GH).

Pulsatility is a fundamental property of the majority of hormone secretion and denotes the recurrence of individual punctuated events interrupting a more or less constant baseline process.

Question 23

Hormone transport

Answer 23

The majority of hormones are peptides= hydrophilic
Cathecolamines= hydrophilic
—> they can travel through the bloodstream easily since they are water soluble
They are usually degraded by enzymes in the blood and tissues and rapidly excreted by kidneys and liver

Steroid and thyroid hormones are hydrophobic= lipid soluble
—> to travel through the bloodstream they bind to transport proteins = become water soluble
Only unbound hormones can leave the blood capillary and get to the target cell
Bound hormones are cleared at much slower rates

Question 24

Concentration of a hormone in the blood

Answer 24

Two factors can increase or decrease the concentration of a hormone in the blood.

1) Rate of hormone secretion in the blood
2) Rate of removal of hormone in the blood a.k.a metabolic clearance rate

Question 25

Metabolic clearance rate= milliliters of plasma cleared of the hormone per minute

Answer 25

Rate of disappearance of the hormone from the plasma/ plasma concentration of the hormone

Question 26

Clearance ways

Answer 26

Hormones are cleared from the plasma 1) metabolic destruction by the tissues 2) binding with the tissues 3) excretion by the liver into the bile 4) excretion by the kidneys into the urine 5) sometimes degraded at target cells by endocytosis of cell membrane hormone- receptor complex: the hormone is metabolized in the cell while the receptor is recycled back to the cell membrane

Question 27

Non lipid soluble hormonal action

Answer 27

Peptides and cathecolamines have receptors in or on the cell plasma membrane. Therefore they cannot have a direct effect inside the target cell. They use intracellular intermediaries to exert effects. CASCADE MECHANISM Among the second messengers ( the intracellular intermediaries) there is cAMP; calcium ions and associated calmodulin; products of membrane phospholipid breakdown

Question 28

The number and sensitivity of hormone receptors are regulated Downregulation

Answer 28

Receptors can be destroyed, inactivated vs manufactured, activated In general this effect is due to binding of the hormone The down-regulation can result from 1) inactivation of receptors 2) inactivation of intracellular protein signaling molecules 3) sequestration of the receptor inside the cell (cell membrane receptors) 4) destruction of receptors by lysosomes after being internalized 5) decreased production of receptors —> tissue’s responsiveness to hormone decreases The up-regulation can result from 1) activation of receptors 2) manufacture of receptors —> tissue becomes more sensitive to hormone

Question 30

G protein-linked hormone receptors

Answer 30

Receptors that indirectly regulate activity of other proteins (enzymes or ion channels) by coupling with groups of cell membrane proteins (G proteins= heterotrimeric GTP binding proteins) 7 transmembrane segments STEPS: Ligand binds to receptor—> change of conformation of GPCR—> activation of G protein through replacement of GDP with GTP in alpha subunit (stimulatory or inhibitory)—> alpha subunit associates to other target proteins and regulates them

Question 31

Ion channel-linked receptors

Answer 31

Virtually all the neurotransmitter substances such as acetylcholine and norepinephrine combine with receptors in the post synaptic membrane. This causes a change int eh structure of the receptors either opening or closing the ion channels. The movement of the ions causes the subsequent effects. Sodium, calcium and potassium ions channels.

Question 32

Enzyme-linked hormone receptors

Answer 32

Some receptors, when activated, function directly as enzymes or are closely associated with enzymes that they activate. Example: leptin Leptin binds to leptin receptor—> conformational change enables phosphorylation and activation of JAK2 molecules—> phosphorylation of tyrosine residues by JAK2—> phosphorylation of STAT—> transcription by leptin target genes to initiate protein synthesis Phosphorylation of JAK2 also leads to activation of other intracellular enzyme pathways such as MAPK and PI3K

Question 33

Adenylyl cyclase-cAMP second messenger system

Answer 33

Binding of the hormone to the GPCR allows coupling of the receptor to the G protein. ``` Gs protein= stimulatory G protein G protein (activated) couples to GPCR—> stimulates adenylyl cyclase—> conversion of ATP to cAMP inside the cell—> activation of cAMP protein dependent kinase—> phosphorylation of specific proteins triggering biochemical reactions in the cells CASCADE OF ENZYMES ``` Inhibitory G proteins—> adenylyl cyclase will be inhibited reducing the formation of cAMP—> inhibitory action in the cell

Question 34

Cell membrane phospholipid second messenger system

Answer 34

Some hormones activate transmembrane receptors that activate the enzyme phospholipase C—> catalyzes the breakdown of phospholipids in the cell membrane especially PIP2 into inositol triphosphate (IP3) and diacylglycerol (DAG) IP3 mobilizes calcium ions from mitochondria and ER. Calcium ions have their own second messenger effect DAG activates PKC. PKC phosphorylates proteins and its lipid portion is the precursor for prostaglandins and other hormones

Question 35

Calcium- calmodulin second messenger system

Answer 35

Calcium entry through change in membrane potential that opens calcium channels or through hormone interacting with membrane receptors that open calcium channels As they enter calcium ions bind to calmodulin (3 out of 4) —> change in conformation—> activation or inhibition of protein kinases—> activation or inhibition of proteins involved in the cell’s response. Example: myosin light chain kinase- acts on myosin—> contraction of smooth muscle Normal calcium concentration 10^-8.. when it rises to 10^-6 enough binding occurs to see the action of calmodulin and troponin C (skeletal muscle contraction)

Question 36

Steroid hormones

Answer 36

Steps: 1) steroid hormone diffuses across cell membrane and enters the cytoplasm 2) steroid hormone binds to receptor 3) combined receptor protein-hormone diffuses into or is transported in nucleus 4) the combination binds at specific points of DNA strands in the chromosomes which activates the transcription process of specific genes to form mRNA 5) The mRNA diffuses into the cytoplasm, where it promotes the translation promotes the translation

Question 37

Thyroid hormones

Answer 37

Thyroxine and Triiodothyronine bind with the receptor proteins in the nucleus ( activated transcription factors) located within the chromosomal complex and they control the function of the gene promoters Activate genetic mechanisms for the formation of many types of intracellular proteins (enhanced intracellular metabolic activity) Once bound to their receptors the thyroid hormones can continue to express their control functions for days or even weeks