Serkan SAYINER, DVM PhD. Assist. Prof.Near East University, Faculty of Veterinary Medicine, Department of Biochemistry

serkan.sayiner@neu.edu.tr

Hormones

• Hormones, secreted by special glands, constituting regulatory impact to the organs and tissues that is reached by the bloodstream and also they are working with very low amounts of organic compounds.▫ In Latin language Hormaine = Alert (Activation)

▫ Hormones are similar to vitamins and enzymes.

▫ The effected tissues by the hormones are called target tissues. Some hormones act as a they do locally. For example: Acetylcholine, Secretin, Cholecystokinin.

▫ Hormones generelly secreted from special glands into the bloodstream and by this they reach to the target tissues.

▫ The medical subject name that is related to hormones is called ENDOCRINOLOGY. ENDOCRINE SYSTEM is the name of related system.

Introduction

Endocrine System

Image Sources: Veterinary Online, Wikipedia, Oklahoma State University

• Blood formation and secretion of hormones occur depending on

the hierarchical control mechanism.

• Large part of the group of hormones on the control mechanism

are released into the bloodstream as listed from top to bottom.

• The hypothalamus is located at the very top forming the base of

the brain. Any neural stimulation reached here, activates the

releasing factors (RFs) and leads to secretion of specific

hormones in very small amounts.

• RFs located in sella tursika alerts pituitary gland (Frontal lobe).

Each RFs stimulate different specific hormone secretion from

the pituitary gland.

Control Mechanism of Hormones

Control Mechanism of Hormones

Source: NeuropetVet

• Hypothalamus do not secrete only the RF but also decelerates hormone secretion (Inhibitory role) and plays a role in the release of hormones or factors.

• However, the posterior lobe of the pituitary hormone oxytocinand ADH is synthesized by the hypothalamus and transported to the posterior lobe of the pituitary neural pathways and then are released into the vessel and capillaries needed.

• Some of these hormones are not involved in this hierarchical axis (Hypothalamic-pituitary axis) Ex. Insulin, glucagon and adrenaline.

Control Mechanism of Hormones

Hypothalamic-Pituitary Axis

• Hypothalamus: TRH, GHRH, GHIH (Somatostatin), CRH, Oksitosin, ADH

• Anterior Hypophysis:GH, TSH, ACTH, FSH, LH, PRL

• Posterior-Hypophysis: Oksitosin, ADH

• Pars intermedia: MSHSource: Prof. A.C. Brown

Hypothalamic-Pituitary Axis

Posterior Lobe

Anterior Lobe

Hypothalamus

Reference: Prof. Dr. Erol ALAÇAM

Hypothalamus

Adenohypophysis

Neurohypophysis

Portal Vessels

Reference: Prof. Dr. Erol ALAÇAM

Secondary Messengers

Intracellular messengers

c-AMP(Cyclic adenosine monophosphate)

Ca2+ Others

Calmodulin

Pathway

c-Kinase

Pathway

• c-AMP (Cyclic adenosine monophosphate) Messenger system▫ 1956 –> Liver

▫ It is regulatory in too many cellular reactions.

▫ Intracellular alterations do not affect c-AMP amount.

▫ Extracellular alterations affect its concentration.

▫ Two enzymes regulate c-AMP levels.

Secondary Messengers

ATP c-AMP 5'-AMP

Adenylyl cyclase PhosphodiesteraseMg2+ Mg2+

• c-AMP plays a role as an intermediary substance on the effect of

peptide hormone, exocrine and endocrine secretion, in the

secretion of neurotransmitters and the synapse for neuronal and

neuromuscular joints.

• Adenylyl cyclase is bound to cell membranes.

• Phosphodiesterase enzyme is found in the cytoplasm.

• When the cell is stimulated, c-AMP synthesis is increased by the

activation of Adenylyl cyclase.

• Protein kinase, phosphorylates many proteins in the cells.

• Ex.: Adrenalin in liver, PTH in renal tubulles.

Secondary Messengers

• The effect of c-AMP differs according to the cells.

• Ex.: Glucagon increases glucose synthesis in liver and thus in the

bloodstream. In adrenal cortex, it stimulates steroid hormone

synthesis.

Secondary Messengers

Process Effect Explanation

Glycogenolysis,

Gluconeogenezis

Stimulate Adrenaline, glucagon increases c-AMP. Insulin has

reverse effect. It decreases.

Enzyme synthesis in liver Increases Transaminase and carboxykinase synthesis increases.

Thyroxine synthesis Increases c-AMP level is increased by the action of TSH.

Skeletal muscle Contraction c-AMP increases the permeability of sarcoplasmic

reticulum against Ca2+ and initiates contraction.

•Calcium Messenger System

▫ There are two different pathways.

Calmodulin and c-Kinase.

▫ There are 2 ways in calcium homoestasis.

1. The removal of calcium through cell

membrane by pumping.

2. Storing in intracellular organelles

(mitochondria and endoplasmic reticulum)

▫Calcium ions, act as an intracellular

messenger and this task is done

through Calmodulin.

Secondary Messengers

• Initiation of muscle contraction,

• Movement of chromosomes,

• Glycogen metabolism,

• Secretion and synthesis of neurotransmitters

• Regulating c-AMP levels,

• Role of calcium in secretion of insulin

• Calcium, activates calmodulin. This activates the inactive

protein enyzme.

▫ Ex. Phosphodiesterase.

Secondary Messengers

• c-Kinase (Protein kinase c/poliphosphoinositide messenger system)

▫ Activated directly by the calcium.

▫ It should have diaclyglycerol and phospholipids to be activated.

Therefore, enzyme is called phospholipid dependent protein kinase-c.

▫ Except brain, kidney and liver tissues, inactive protein kinase-c is found

freely.

▫ When Calcium messenger system is alerted by the hormones, membrane

diacylglycerol increases and causes protein kinase-c bound to inside of

the membrane.

▫ When required phospholipids are found in the membrane, calcium

dependent c-kinase is fully activated.

Secondary Messengers

• Many hormones are found in the vesicles which are bound tomembranes.

• Some of them are not taken into the vesicles, and found in themolecular form.

• Peptide and protein hormones are taken straight into vesicles in the ER. In here goes to Golgi complex and condenses into prepared vesicles. It is connected to the membrane and secreted outside the cell if necessary.

• Steroid hormones are directly passes through membrane.

• Hormones in the bloodstream is still attached to the proteinsand when they reach to the target tissue, they are removedfrom protein and become active.

Storage of Hormones

Source: Boundless

• Secretion of hormones is controlled by the feed-back

mechanism.

• A raise in the hormonal level in the blood and signal from the

target tissue cause the inhibition of secretion and synthesis of

hormones. Negatif Feed-Back.

• A decrease in the hormone level in the blood alerts secretion of

hormones by the Positive Feed-Back.

Regulating the Secretion of Hormones

• Intracellular and extracellular messenger

system is controlled by the receptors.

• Receptors take the information from outside.

(Hormone, neuronal, electrical

differences...).

• Receptors are generally protein molecules.

• Receptos are not only found in the

membranes but also found in cytosol.

• All hormones have their specific receptors

found in the cells that they affect.

Cell Receptors

Source: Medillsb

1. HORMONES WITH CELL SURFACE RECEPTORS (Adenylyl cyclase system)

• This sytem causes formation of intracellular cyclic-AMP (c-AMP)’ and also involves in the activity of many enzymes.

• Specially, anterior and posterior pituitary hormones, PTH, Glucagon, adrenaline and hormone releasing factors are influenced by this type of receptor systems.

• In this sytem, there is a specific receptor on the cell membrane according to each hormone. Hormone-receptor complex activates the to adenylyl cyclase. This enzymatic action converts ATP to c-AMP.

Mechanism of Hormone Action

2. HORMONES WITH INTRACELLULAR RECEPTORS (Protein synthesis system)

• Receptors are located inside target cells, in the cytoplasm or nucleus.

• In this system, steroid hormones are more effective.

• The major consequence of activation (hormone-receptor complex) is that the receptor becomes competent to bind DNA.

• Activated receptors bind to "hormone response elements", which are short specific sequences of DNA which are located in promoters of hormone-responsive genes.

• Transcription from those genes to which the receptor is bound is affected. Most commonly, receptor binding stimulates transcription. The hormone-receptor complex thus functions as a transcription factor.

Mechanism of Hormone Action

Video Source: Youtube

Video Source: Youtube

Video Source: Youtube

3. Other Action Mechanisms

• INSULIN, instead of other hormones, it decreases cAMP

when it binds to special receptors on the cell membrane.

Instead of cAMP, cGMP will increase.

• GH (Growth Hormone) transports amino acids intracellularly

in a different way.

• Catecholamines and acetylcholine hormones causes

differences against ions in cell permeability.

Mechanism of Hormone Action

Source: Usmle

Video Source: Youtube

• There are different types of classifications.

1. Glandular Hormones

2. Tissue Hormones

Classification of Hormones

1. Steroid Hormones

2. Amino acid derivative hormones

3. Peptid-Protein Structured hormones

1. HYPOTHALAMUS HORMONES;

i. Luliberin/GnRH: Decapeptide. Stimulates secretion of FSH ve LH.

ii. Corticoliberin (CRF): Peptide structure. Stimulates secretion of ACTH.

iii. Thyroliberin (TRH): Tripeptide. Stimulates secretion of TSH.

iv. Somatoliberin (GHRH): Decapeptide. Stimulates secretion of GH.

v. Melanoliberin (Melanotropin): Stimulates secretion of MSH.

vi. Somatostatin (GHIH): Inhibits GH secretion.

vii. Prolactin releasing hormone (PRLH): Stimulates Prolactin secretion.

viii.Prolactostatin (PRIH): Inhibits prolactin secretion.

ix. Dopamin: Neural hormone. Supresses PRL secretion.

x. Oxytocin

xi. Vazopresin

Classification of Hormones

2. PITUITARY GLAND HORMONES

i. Neurohyphophysis: Oxytocin and Vasopressin (ADH)

ii. Pars intermedia hormones: MSH (Melanocyte stimulating

hormone)

iii. Adenohypophysis;

a. Metabolic hormones: GH, TSH, ACTH

b. Gonadal hormones (Gonadotropics): FSH, LH, LTH (PRL)

3. THYROID GLAND HORMONES

i. Triiodothyronine (T3),

ii. Thyroxine (T4),

iii. Calcitonin (CT)

Classification of Hormones

4. PARATHYROID GLAND HORMONES

i. Parathyroid Hormon/Parathormon (PTH)

5. PANCREAS HORMONES

i. Glucagon (from α-cells)

ii. Insulin (from β-cells)

iii. Somatostatin (δ-cells)

iv. Pancreatic Polypeptide

6. OVARIAN and TESTES HORMONES

i. Estrogens, Gestagens

ii. Androgens

Classification of Hormones

7. ADRENAL GLAND HORMONES

i. Adrenal Cortex

a. Glucocorticoids: Cortisone, Corticosteron, Cortisol

b. Mineralocorticoids: Aldosterone, 11-deoxycorticosterone

c. Androgens and estrogens

ii. Adrenal Medulla;

a. Catecholamines: Adrenaline, noradrenaline

8. PINEAL GLAND

i. Melatonin

Classification of Hormones

9. NEUROHORMONESi. Acetylcholine, noradrenaline, γ-aminobutyric acid (GABA)

10.GASTROINTESTINAL HORMONESi. Gastrin

ii. Secretin

iii. Cholecystokinin (Pancreozymin)

iv. Enterogastrone

v. Parotin

vi. Enterocrinin

vii. Somatostatin

viii.Gastric inhibitory polypeptide (GIP)

ix. GHRELIN (Hunger hormone)

Classification of Hormones

11. ADIPOSE TISSUE HORMONESi. Leptin: It is oppesed by the actions of the hormone ghrelin. It helps to

regulate energy balance by inhibiting hunger.

12. TISSUE HORMONES THAT AFFECT BLOOD VESSELSi. Bradykinin: A peptide hormone that causes blood vessels to dilate.ii. Serotonin (5-hydroxytryptamine/5-HT): It is primarily found in the

gastrointestinal tract (GI tract), blood platelets, and the central nervous system (CNS). It causes the contraction of smooth muscles in vessels, airways and digestive tract. Excess causes excitation, deficiency causes depression.

iii. Histamine: It is involved in the inflammatory response and has a central role as a mediator of pruritus. As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. Histamine increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues

iv. Prostaglandins (PG): Found almost in all tissues. Vasodilator and allow contraction of smooth muscles.

Classification of Hormones

• Pituitary gland, shows the effect control over the entire endocrine system. It has a central role in the endocrine system. It manages many endocrine glands and tissues. It is also called as «the president gland».

• Releasing hormones or factore from hypothalamus affect onpituitary gland to cause hormone synthesis and secretion. Various centers are located in the hypothalamus participating the regulation of important functions.

• These are;▫ Centers that the occurrence of reproductive and sexual behavior is

regulated,▫ Centers that regulate metabolism,▫ Centers that regulate the intake of nutrients,▫ Centers for the compliance with various state organs,▫ Centers that regulate receiving and disposal of water.

Pituitary Gland Hormones

• Numerous major hormones are

secreted from this lob. They have

protein like structure.

•The frontal lobe is under

the control of the

hypothalamus.

Anterior Pituitary (Adenohypophysis) Hormones

Image source: Prof. A.C. Brown

1. ACTH (Adrenocorticotropic hormone): Its secretion is under

control of Corticotropin-releasing factor (CRF) which is

synthesized from hypothalamus. It consists of 39 amino acids in

the form of the prohormone. 23 amino acids required for the

effect.

▫Main effects;

Target organ is the adrenal cortex.

It increases steroid hormone synthesis.

Synthesis of glucocorticoids is increased.

Ascorbic acid amount in the adrenal glands is reduced.

It is involved in the acceleration of protein synthesis.

Anterior Pituitary (Adenohypophysis) Hormones

2. Somatotropin/Growth hormone (STH - Growth hormone /

GH): Polipeptide structure. Secretion is under control of

Growth hormon-Releasing Factor (GHRF) which is synthesized

by hypothalamus.

▫ The amino acid numbers it carries varies between animal species.

▫ For example; Human growth hormone 188, bovine growth hormone

369 and sheep growth hormone 191 amino acids.

▫ Human and monkey GH is composed of a single polypeptide chain,

however in cattle and sheep there are two-chain structure.

Anterior Pituitary (Adenohypophysis) Hormones

• Main effect;

▫ To increase protein synthesis in all cells present in the body.

▫ To increase the mobilization of fat and allow their use (lipolysis).

▫ Reducing carbohydrate utilization. It’s the antagonist of Insulin.

▫ It increases extracellular collagen and chondroitin sulfate synthesis.

▫ It is involved in water balance. While the tubular secretion is

increased, K, Na ve Cl retention occurs.

▫ GIGANTISM, ACROMEGALY, and DWARFISM.

Anterior Pituitary (Adenohypophysis) Hormones

Image source: Anonim Image source : Koiran Geenit

Image source : Voorbij ve ark., 2011

Image source : AnimalEndocrinClinic

3. Thyroid Stimulating Hormone (TSH - Thyrotropin): It has a

Glycoprotein structure. It consists of 8% carbohydrates.

Secretion depends on Thyrotropin-Releasing Factor (TRH)

which is produced by Hypothalamus.

▫ Main effects;

It effects on thyroid gland therefore it stimulates thyroxine (T4) and

triiodothyronine (T3) hormones.

It accelerates the basal metabolism.

It accelerates the cardiac cycle.

It stimulates the nervous system function.

It decreases liver glycogen.

Anterior Pituitary (Adenohypophysis) Hormones

4. Follicle Stimulating Hormone (FSH): It has a glycoprotein

structure. Secretion is under control of Follicle Stimulating

Hormon-Releasing Factor (FRF)/GnRH secreted by

hypothalamus.

▫ Main effects;

In males; stimulates and regulates spermatogenezis.

In females; affects on development of follicles in ovaries.

Anterior Pituitary (Adenohypophysis) Hormones

5. Luteinizing Hormone (LH): It is a glycoprotein hormone.

Secretion is under control of Follicul Stimulating Hormon-

Releasing Factor (FRF)/ GnRH secreted by hypothalamus.

▫ Main effects;

In males; production of testosterone in testicles.

In females; stimulates follicles to synthesize estrogen and development

of Corpus luteum.

Anterior Pituitary (Adenohypophysis) Hormones

6. Luteotropic Hormone (LTH) (Luteotropin/Prolactin (PRL): It is

a peptide hormone. It is under the control of PRLH secreted by

hypothalamus.

Anterior Pituitary (Adenohypophysis) Hormones

• Main effects;

• It affects the proliferation of the mammary gland with estrogens. It allows the development of udderand stimulates the secretion of milk.

• Stimulates corpus luteum for the production of progesterone and causes continuity of its secretion.

• It is the hormone that starts lactation phase in females.

• It stimulates the formation of the crop in pigeons.

• Allows the instinct of maternity/nesting.

Image Source: Pixabay

• Melanocyte Stimulating Hormone (MSH/Melanotropins/Intermedins/ Melanophore Hormones): The structure of α-MSH is same for all species and consists of 13 amino acids. Pig β -MSH consists of 18 amino acid. But inhumans, N-terminal of hormone is longer than pigs (4 more amino acids).▫ Its secretion depends on light stimulation.

▫ Main effects; MSH is a hormone that affects the skin's pigmentation.

Fish, amphibians and reptiles, affects the distribution of pigment granules in pigment cells

Melanophore, iridophores. Melanocytes

Pars Intermedia (Intermediate pituitary) Hormones

• Posterior pituitary (neurohypophysis) includes pituicytes (Glial cells of posterior lobe). The posterior pituitary is not glandular as is the anterior pituitary. It is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior pituitary, and is also a store for the later release of neurohypophysial hormones.

• Vasopressin (Anti-diuretic hormone/ADH): Vasopressin secretion siteis the region found in hypothalamus and called the supraoptic nucleus. It is a nonapeptide and an alkaline due to the presence of arginine in the structure.

• Main effects;▫ Inhibits urine. Enhance water reabsorption with mineralocorticoids.

▫ Raises the blood pressure (weaker than adrenalin but longer time).

▫ Controls Na concentration in the extracellular fluid.

Posterior Pituitary (Neurohyphophysis) Hormones

• Oxytocin: Its production location is the region called the

paraventricular nucleus of the hypothalamus. It has nonapeptid

structure. Amino acid type found at 8th. position determines the

species specificity.

▫ Main effects;

It provides the contractions of the uterus. This effect is called oxcitoxic

effect and it can compress uterine mucsle in pregnancy.

Uterus must enter a pre-estrogenic effect to show this effect during parturition.

It also causes the uterine contractions during sexual intercourse.

Oxytocin facilitates the flow of milk by contracting mammary gland muscles.

Triggers cells surrounding the alveoli and milk ducts (myoepitheliım cells) to

contract.

Reduces blood pressure.

Back Lop pituitary (neurohypophysis) hormones

1. Gastrin: It is a polypeptide. Secreted from pyloric mucous. It

causes HCl secretion from fundus cells.

2. Secretin: It is a polypeptide and secreted by the duodenum. It

controls the volume of pancreatic secretion and bicarbonate

levels.

3. Cholecystokinin (Pancreozymin): It is a polypeptide and

secreted by the duodenum. It has effects on gall bladder

(allows the discharge from ductus choledochus/common bile

duct) and on pancreas (enzyme secretion).

4. Enterogastrone: It is a polypeptide and secreted by the

intestine. Inhibits the prodution of gastric secretion and HCl.

Gastrointestinal Hormones

6. Parotin: It is a polypeptide. It is secreted by the salivary glands. Stimulate the calcification of teeth, lowers serum Ca levels, raises the serum P level.

7. Enterocrinin: Secreted from the intestinal mucosa as a protein hormone. It increases the secretion and excretion of jejunaland ileal discharge and the enzyme content.

8. Somatostatin: Inhibits gastrin ve secretin synthesis.

9. Gastric inhibitory polypeptide (GIP): Secreted by duedenumand jejenum. Stimulates Insulin secretion.

10.Ghrelin: Secreted mainly by stomach and duedenum. It is called as hunger hormone. It is involved in the regulation of energy balance.

Gastrointestinal Hormones

• Tyroid gland is found as a right and left lobulus at the end of the larynx and the begining of the trachea.

• Triiodothyronine (T3) and Thyroxin (T4): 3 and 4 iodine elements are carried by these hormones. They are an amino acid (Tyrosine) derived hormones. ▫ Under normal conditions, the amount of the

synthesis of T3 is 1/3 of the T4 synthesis.

▫ The effect of T4 is slow and acts for a long time.

▫ The effect of T3 is fast but it has a short term effect.

Thyroid Gland Hormones

Image source: MedCell Yale

Image Source: Boundless

Biosynthesis of Triiodothyronine (T3) and Thyroxine (T4)

• Thyroid hormones circulate in the blood attached to the plasma

proteins.

• Thyroxine mostly passes through the blood. Enzymatic

reactions that takes place in either thyroid gland or other

tissues can seperated an iodine from thyroxine and forms

triiodothyronine.

• The actual metabolic impact, the real hormone effect, is

thought to be created by T3.

• The ways for catabolism is the deamination and

decarboxylation.

• Metabolites are removed by the kiney and bile.

Thyroid Gland Hormones

• Effects;

▫ Stimulates intake of substrates by mitochondrias, oxidation and ATP

production.

▫ To accelerate protein synthesis. This increase happens with the

raise of the synthesis of the enzymes at the same time. In protein

synthesis, thyroid hormones increases so this causes tissues to get

larger in size and also causes closure of epiphysis of the bones in a

very short time.

▫ It affects all the phases of carbohydrates metabolism. The usage of

glucose also increases.

Firstly, glycogenolysis increases.

Gluconeogenesis increases (relation with Diabetes mellitus ???).

Thyroid Gland Hormones

• Effects;

▫ It affects synthesis, mobilization and oxidation processes in the

lipid metabolism. This effect is madee through c-AMP. Decreases

blood cholesterol.

▫ Increases the synthesis of many enzymes. Depending on the

excessiveness of thyroid hormones, thiamine, riboflavin, cobalamin

and ascorbic acid need is increased.

▫ It is required for the synthesis of vitamin A from Carotene.

Thyroid Gland Hormones

• Calcitonin (CT);

▫ Polipeptide structure. Forming from 32 amino acids.

▫ It is synthesized from C-cells located between follicular cells

excepting in fish, amphibians, reptiles and birds.

▫ It is opposed by the actions of PTH on serum Ca levels.

▫ Calcitonin secretion by the thyroid gland is dependent on the

concentration of blood calcium.

▫ If calcium ions in the blood found within the physiological limits,

calcitonin secretion is very low.

▫ If blood calcium increases, calcitonin secretion significantly

increases to reduce calcium level.

Thyroid Gland Hormones

• Effects;▫ There is a quick impact on the Serum Ca levels, there will be a drop

for a short time.

▫ If the Ca content of the blood increases, the synthesis increases.

▫ Provides calcium increase in bones.

▫ Inhibits mobilization of Ca from bones.

▫ Prevents hypercalcemia.

• As the age gets older, the reaction skills of the bone tissue decreases against calcitonin.

• In poultry, calcitonin is less effective during nesting/laying an egg.

Thyroid Gland Hormones

• Parathyroid gland, located in the rear surface of the thyroid

gland. It has four small ovary shape.

• Parathyroid hormone/Parathormone (PTH);

▫ Consisting of a single chain peptide without cysteine.

▫ Amino acid sequence varies according to animal species.

▫ PTH regulates the Ca2+ metabolism and blood Ca2+ level control

the secretion of PTH.

▫ Affects calcium and phosphorus metabolism.

▫ Affects kidney, bone and gastrointestinal tract.

Parathyroid Gland Hormone

▫ PTH functions;

Effects on Kidney : Controls the removal of phosphorus, potassium,

calcium and hydrogen ions.

Effects on Bones : Affects calcium transport in bones. It causes the

removal or mobilization of calcium phosphate from the bones.

Effects on Gastrointestinal channel: Increases the Vitamin D synthesis

and facilitates calcium absorption in the intestine.

▫ The concentration of ionized calcium in the blood, controls the

secretion of PTH by negative feed-back.

Parathyroid Gland Hormones

1. INSULIN

• It is secreted by β-cells of langerhans islets

of the pancreas.

• It is synthesized in the form of pro-insulin by

21 amino acid in A-chain, 30 amino acid in

B-chain and 31 amino acid of C-peptide

chain.

• There is no C-peptide chain in the active

form.

Pancreas Hormones

Image Source: Library.Med.Utah

Source: Annals

Pancreas Hormones

Source: Diapedia

Source: Usmle

Video Link: Youtube

• INSULIN effects;▫ Effects on cell permeability: It causes glucose molecules to taken

up inside the cell. It also causes monosaccarides, amino acids and fatty acids to taken up by the insulin dependent organs like liver, muscle, nerve and adipose tissue.

▫ Effects on carbohydrate Metabolism: Activates glycolysis and pentose-phosphate pathway to metabolise glucose. It activates and inhibits key enzymes found in glycolysis and pentose-phosphate pathway (Activation: Hexokinase (??) and isoenzyme glucokinase, phosphofructokinase-1 (PFK-1), pyruvate kinase (PK); Inhibition: pyruvat carboxlyase, phosphoenolpyruvate carboxylase, F-1,6-di Pase).

Pancreas Hormones

• INSULIN effects;

▫ Effects on lipid metabolism: Increases fatty acid synthesis. Insulin

activates key enzymes and causes breakdown of glucose; the product

of this reaction, acetyl-CoA synthesis is increased. Therefore, this

speeds up the synthesis of fatty acids. Free fatty acids is stored as

triglycerides and by this way ketosis is prevented.

▫ Effects on protein metabolism: It occurs as a result of the increase

of the amino acids in the cells and also increase in permeability of

the cell membrane. Directly, causes increase in mRNA synthesis ve

increase in the entry of amino acids inside of cell proteins.

• Deficiency;

▫ Diabetes mellitus

Pancreas Hormones

2. GLUCAGON: It is secreted from α-cells of Langerhans islets. It

effects opposite way of Insulin. It increases blood glucose

levels. It is a hormone that is made up of 29 amino acids.

▫ Effects:

It activates key enzymes in gluconeogenesis (pyruvate carboxylase,

phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase,

glucose-6-phosphatase).

The effect on glycogenolysis is done by activating adenylyl cyclase,

increasing the production of c-AMP, activating protein kinase and

lastly activating phosphorylase a and phosphorylase b.

Glucagon also stimulates the entry of fatty acids to mitochondrias and

oxidation of fatty acids.

Pancreas Hormones

• It is made up from two different endocrine glands according to

development, function and morphology.

Glandula suprarenalis / Adrenal Gland

Source: Wikimedia

• The origin of the sympathetic nerve and adrenal medulla are the same and they worked together. Therefore it is called sympatico-adrenal system.

• The cells that secreting Catecholamines are the altered sympathetic neurons.

• Epinephrine are mainly secreted from medulla (80%) . Hormone that is secreted from sympathetic nerves is generelly norepinephrine.

• Precursor molecule for both hormone is ................

Adrenal Medulla

TYROSINE

Adrenal Medulla

CatecholDopamine

Norepinephrine Epinephrine

Tyrosine

Dopamine(3,4-dihydroxyphenethylamine)

Norepinephrin

e

Epinephrine

L-Dopa(3,4-dihydroxyphenylalanine)

Tyrosine hydroxylase

Dopa carboxylase(Pyridoxal phosphate)

Dopamine-β-hydroxylase(Ascorbic acid)

Phenylethanolamine

N-methyltransferase

(Methylation with S-adenosyl methionine)

• Control of the secretion of Catecholamines;▫ At rest they are very low in level. Activated sympathetic system increases

their synthesis and secretion.

▫ Receptors play a role in alerting the system. These receptors include glucose receptors, thermoreceptors, baroreseptors. Hormones are determined by the stimulated receptors.

▫ Fight or Flight Response

▫ Norepinephrine hormone is secreted when arteria carotis pressure receptors are stimulated.

▫ Sympathetic nerves and glucocorticoids arrange catecholamine synthesis. Tyrosine hydroxylase is affected by mainly nerves and less glucocorticoids.

Dopamine-β-hydroxylase activation is regulated by both nerves and glucocorticoids.

Phenylethanolamine N-methyltransferase activation is mostly regulated by glucocorticoids.

Adrenal Medulla

• Effects;▫ Sudden decrease in blood glucose causes increase in secretion of

adrenaline and this stimulates glycogenolysis. It’s an insulin antagonist. Noradrenalin has no importance on this effect.

▫ Adrenalin increases metabolic speed by ~ 30% . Noradrenalin has no importance on this effect.

▫ Increases cardiac cycle and also blood pressure. The pupils are dilated.

▫ Increases tones and contractions of smooth and skeletal muscles.

▫ Bronchials expand and this increases venting capacity of lungs.

▫ Blood circulation in skin increases and formation of sweat increases.

▫ Adrenalin and noradrenalin raises lipolysis. By this way heart muscle can take up energy from fatty acids.

Adrenal Medulla

• STEROID derived hormones are synthesized and secreted.

• The most important hormones are Cortisol, Corticosterone,

Cortisone and aldosterone. They have an important role on

carbohydrate and protein metabolism.

• Classification

▫ MINERALOCORTICOIDS: Hormones that regulate inorganic

metabolism.

▫ GLUCOCORTICOSTEROIDS: Hormones that regulate carbohydrate,

lipid and protein metabolism.

▫ They consist of 21 C atoms.

Adrenal Cortex

Steroid Ring

System

Zona fasciculata

3β-Hydroxysteroid

dehydrogenase/

Δ5-4 isomerase

Cytochrome

P450ssc (Cholesterol

desmolase)

P450c21

P450c11

P450c17

(17α-hydroxylase)

3β-Hydroxysteroid

dehydrogenase/

Δ5-4 isomerase

P450c21

P450c11

11β-hydroxysteroid

dehydrogenase

Zona glomerulosa

3β-Hydroxysteroid

dehydrogenase/

Δ5-4 isomerase

Cytochrome

P450ssc (Cholesterol

desmolase)

P450c21

P450c11

Aldosterone synthase

Zona reticularis

Cytochrome

P450ssc (Cholesterol

desmolase)

P450c17

(17α-hydroxylase)

P450c17

(17,20 Lyase)

Sulfotransferase

3β-Hydroxysteroid

dehydrogenase/

Δ5-4 isomerase

Steroid sulfatase

3β-Hydroxysteroid

dehydrogenase/

Δ5-4 isomerase

17β-hydroxysteroid

dehydrogenase

5α-Reductase

17β-hydroxysteroid

dehydrogenase

3β-Hydroxysteroid

dehydrogenase/

Δ5-4 isomerase

Aromatase

Aromatase

Fetal liver and

placenta

17β-hydroxysteroid

dehydrogenase

Androgen & Estrogen

Biosynthesis

Enzyme Activity Primer expression place

Steroidogenic acute regulatory proteinIt stimulates cholesterol uptake into

mitochondria.

All tissues except the brain and placental

steroidogenic

desmolase, P450ssc Cholesterol-20,23-desmolase Steroidogenic tissues

3β-hydroxysteroid dehydrogenase type 1 3β-hydroxysteroid dehydrogenase Steroidogenic tissues

P450c11 11β-hydroxylase Only in zona fasciculata and zona reticularis

P450c17 Two activity: 17α-hydroxylase and 17,20-lyase Steroidogenic tissues

P450c21 21-hydroxylase Absent in Zona reticularis

Aldosterone synthase 18α-hydroxylase exclusive to zona glomerulosa of adrenal cortex

Estrogen synthetase Aromatase Gonads, brain, adrenal gland, adipose tissue, bone

17β-hydroxysteroid dehydrogenase type

317-ketoreductase Steroidogenic tissues

Sulfotransferase Sulfotransferase Liver and adrenal gland

5α-reductase type 2 5α-reductase Steroidogenic tissues

The primary enzymes involved in the biosynthesis of steroid

hormones

• MINERALOCORTICOIDS

▫ They are synthesized from outside part of the cortex. The most

affected hormone is Aldosterone. Other hormone that is effective

5% of Aldosterone is 11-deoxycorticosterone.

▫ These hormones are the corticoids that affect electrolyte

metabolism.

▫ Synthesis and secretion of Aldosterone;

Depends on mostly Na+ and K+ ions. Decrease in concentration of Na+

ions or increase in the concentration of K+ ions raises the secretion of

aldosterone.

Secretion of aldosterone is also depends on blood pressure. Increases

blood pressure (via the Renin-angiotensin-aldosterone system).

Adrenal Corteks

• Effects;

▫ Increases active transport of Sodium.

▫ Allows renal tubular retention of Na. This will cause increased

osmotic pressure. Water is reabsorbed at the same rate with Na to

prevent high osmotic pressure.

▫ To protect the electrochemical balance, K+ and H+ ions is given to

the tubule fluid simultaneously with Na reabsorption.

▫ Reduces to excrete Na+ ions from sweat glands, salivary glands and

intestines. Na + removal increases when deficiency occured.

▫ Aldosterone against heat are important. It is involved in the

prevention of excessive Na losses when an excessive sweating is

occured.

Adrenal Cortex

Source: Aria Rad 2006

Renin-Angiotensin-Aldosterone System

• GLUCOCORTICOIDS▫ They are secreted from the cortex of the middle and inner layers.

This name was given because they stimulate Gluconeogenesis.

▫ The most important representatives are; 17-hydroxycorticosterone/cortisol/hydrocortisone,

Corticosterone,

7-hydroxy-11-dehydrocorticosterone/cortisone.

▫ Effects; Carbohydrate Metabolism;

Stimulates the key enzymes in gluconeogenesis. Specially increases the usage of amino acids for gluconeogenesis and storage of the glycogen. It brings about a reduction in the use of peripherally glucose.

Adrenal Cortex

▫ Lipid Metabolism; Increases lipogenesis when taken in from outside in healthy animals.

▫ Protein Metabolism; Cortisol acts directly to increase protein synthesis in the liver. However, in

muscles, lymphoid and other tissues, inhibits the protein synthesis due to reduction in amino acid transport.

Promotes the destruction of proteins in skeletal muscles and in other tissues,

Increases the secretion of HCl and pepsinogen from the stomach and pancreatic trypsinogen.

▫ Anti-inflammatory effect and role in immune system; Decreases capillary permeability and stabilizes the membranes of lysosomes.

Thus, inflammation is inhibited.

They provide Ca mobilization in the bones.

The excessive amount of synthesis and long influence causes immunosuppression. Besides, RNA and protein synthesis in lymphocytes is reduced.

Adrenal CorteX

• Gonadal hormone production, especially made by interstitial

cells.

• The corpus luteum and placenta takes place as a temporary

place for the hormone synthesis in females.

• Sex hormones may also be synthesized by the adrenal cortex.

• The synthesis of sex hormones stimulated by gonadotropins.

• All of the sex hormones are STEROIDAL. They show a close

relationship with each other and adrenal cortex hormones. They

have common metabolic pathways in the body. Therefore, both

male and female sex hormones found in both males and females

together.

Gonadal hormones

• Progesterone has a key metabolite for the synthesis of all steroid hormones.

• Not only in the ovaries, it is located in both adrenal glands andthe testes. This is the intermediate metabolite in the body to other hormones.

• Androgens occur as intermediates during both degradation of progesteron and cortex hormones and also in the synthesis of estrogens.▫ Therefore, even if in small quantities, it is found in adrenal cortex

and ovaries.

• Androgens and estrogens, respectively, possess 19 and 18 carbon atoms.

Gonadal hormones

• Under the influence of FSH, estrogenic hormones is synthesizedin the ovary during follicular growth. Besides, progesteron is synthesized in Corpus luteum.

• ESTROGENS▫ Theca granulosa cells in ovarium synthesize estrogens.

▫ It is also synthesized in adrenal cortex, testis and placenta during pregnancy.

▫ Most effective form is estradiol-17β (E2). Others are, estrone (E1) and estriol (E3).

▫ Inactivation occurs in the liver. Excreted with urine and feces in the form of esters.

Ovarian Hormones

• ESTROGENS

▫ Estradiol is the active and available form.

▫ Estriol is mainly synthesized from placenta.

▫ Estrone is the very least form. Especially it is known as a

carcinogen. It is closely related to diseases and health status.

Estrone sulfate form has long life and kept as a reservoir for

conversion to estradiol. It is main form in postmenopausal women.

▫ Estrone sulfate is used to detect late pregnancy and also to

investigate the fetus viability in cows, horses, donkeys, pigs and

goats.

Ovarian Hormones

• Effects: ▫ Genital effects of estrogens are to stimulate RNA and protein

synthesis in order to induce the development of genital organs.

▫ Enables the development of the mammary gland combined with glucocorticoids, insulin, progesterone and prolactin.

▫ Act as an light anabolic on muscle, liver and kidneys.

▫ They allow the development secondary female characters. After castration in males, acts as an lipid anabolic.

▫ In fast-growing tissues of the male reproductive organs show an effect which prevents the mitotic event. Therefore it is used to treat prostate cancer.

▫ Increased blood levels reduces FSH secreting by affecting hypothalamus and besides, it increases the secretion of LH.

Ovarian Hormones

• GESTAGENS▫ The most important member is Progesterone. The diposal of gestagens

from the organism is done by the product Pregnandiol. It is removed by the urine.

▫ Progesteron is synthesized in Corpus luteum and it assures the continuitation of pregnancy.

▫ Otherwise it is synthesized by the adrenal glands. It is a precursor of androgens and estrogens .

▫ Effects; The first effect of progesterone is to ensure the continuation of the

pregnancy. Progesteron creates the environment for the settlement of the embryo in the

uterine mucosa which is prepared by estrogens. In case of insufficient progesterone secretion, uterine mucosa not fulfill the conditions for nutrition of the embryo.

The effect of follicle hormone (FSH) is inhibited by progesterone. Itssecretion is triggered by LH.

Ovarian Hormones

• RELAXIN▫ In females ovaries (corpus luteum) and placenta is the

locations that releases Relaxin.

▫ It is necessary for the continuity of the pregnancy.

▫ Sacroiliac joint and symphysis expands during pregnancy. It

facilitates the birth.

▫ In dogs, it is used to detect pregnancy.

▫ In males, it is secreted from prostate. It is important for the

sperm motility.

Ovarian Hormones

• INHIBIN▫ Polipeptide structure.

▫ Granulose cells in the ovary; sertoli cells in the testes are the

locations for the synthesis.

▫ It inhibits the secretion of FSH and activates paracrine function in

gonads.

▫ In mares, it is used in the diagnosis of Granulosa Cell Tumor.

Other Hormones

Ovarian Hormones

F

CL

Resource: Prof. Dr. Erol ALAÇAM

Ovarian Hormones

Illustration Source: Prof. Dr. Erol ALAÇAM

• ANTI-MULLERIAN HORMONE (AMH)

▫ It is a protein hormone.

▫ Granulose cells in the Ovary; sertoli cells in the testes are the

locations for the synthesis.

▫ It has low levels.

▫ In healthy mares, levels during the estrous cycle or pregnancy does

not change (<1 ng/ml) .

▫ In mares, it is used in the diagnosis of Granulosa Cell Tumor with

inhibin. Blood levels are increased (generally >25 ng/mL).

▫ Inhibin and testerones can give misleading results therefore, AMH is

more sensitive test.

Other Hormones

• ANDROGENS

▫ Androgens are the steroids that has 19 C atoms and they are

secreted from

Leydig interstitial cells in testicle.

▫ ‘Androgenic’ name is not only given for the biological activity of

the hormones, it is also given to point that they are steroids with

19 C atoms.

▫ Mainly effective examples of androgens are testosterone (17 β-

hydroxy-androst-4-en-3-one) and androsterone (androst-4-ene-

3,17-dione ) forms.

▫ These are found in Leydig cells and formed from 17-

hydroxyprogesterone.

Testes Hormones

• Effects;

▫ They allow the development of male sex organs.

▫ The extragenital effect is to stimulate the biosynthesis of proteins.

It is an anabolic hormone.

▫ They allow the development secondary male characters.

▫ Testosterone increases the protein synthesis within the cell.

Testosterone operates in the synthesis of RNA from DNA in the cell

nucleus. It increases the transcription.

Testes Hormonları

• Pineal gland affects many reproduction events and it is proved

that it can secrete many hormones at a time.

• This gland cells is the only place of melatonin synthesis and

secretion of the hormone melatonin.

• Synthesis occurs via serotonin and its amount is high in daylight

, on the other hand, is low at night.

• Light intensity and duration changes the amount of serotonin

in pineal gland.

• The amount of Melatonin is indirectly related to serotonin

rythm. Sytnhesis is less during daytime, however synthesis is

more at night .

Pineal Hormones (Pineal Gland)

• Effects:

▫ They stimulate mostly the accumulation of the melanin granules when it is compared to their distribution. They show a different effect other than they show in amphibians. They ensures that skin looks brighter.

▫ Changes in the synthesis of melatonin, provides the information to thehypothalamic-pituitary-gonadal axis about day length. It is a sensitive and complicated biological clock. It converts ambient light into neural activity.

▫ It has a role in reproduction system. In particular, monoestrous or polyestrous animals depending on the season.

▫ In mammalian organisms, Pineal gland is the only structure that melatonin is synthesized and the pituitary luteinizing hormone secretionis inhibited.

Pineal Hormones (Pineal Gland)

• INSULIN-LIKE GROWTH FACTOR ( IGF-1)

▫ It is similar to insulin according to its structure.

▫ Synthesized in the liver.

▫ Growth hormone (GH) stimulates its synthesis and secretion.

▫ Affects the development and growth in youngs.

▫ It has anabolic effects on adults.

▫ It is used in dogs and cats, as a indirectly evaluation for GH

secretion and activitiy.

▫ It is used in the diagnosis of Dwarfism and Agromegaly.

Other Hormones

• ERYTHROPOIETIN ( EPO)

▫ Excreted by the kidneys.

▫ Glycoprotein structure.

▫ Controls erythropoesis.

▫ It is a cytokine for erythrocytes in the bone marrow .

▫ Effects:

It increases the number of proerythroblasts in the bone marrow.

It stimulates RNA synthesis.

It stimulates iron for participation to hemoglobin in peripheral blood.

It stimulates angiogenesis.

Other Hormones

• PROSTAGLANDINS ( PG)▫ They are synthesized from arachidonic acid.

▫ At least 6 primary prostaglandins has being shown. These are PGE1 , PGE2 , PGE3 , PGF1α , PGF2α and PGF3α.

▫ Effects: They are potent vasodilators .

They assure the smooth muscle, especially uterine smooth muscle contractions.

Increase the efficiency of the heart muscle and cause the expansion of the bronchi.

They are antagonists against epinephrine, norepinephrine, glucagon and ACTH. They have impact on the migration of fatty acids from adipose tissue.

They have thermoregulatory effects .

Other Hormones

• PREGNANT MARE SERUM GONADOTROPIN (PMSG)

▫ It is also known as equine chorionic gonadotropin (eCG).

▫ It is produced in the chorion of pregnant mares

▫ It is synthesized in pregnant mares in between 40-130 days.

▫ It can be used as pregnancy diagnosis between these days.

Other Hormones

• Ası. T. 1999. Tablolarla Biyokimya, Cilt 2

• EclinPath. http://www.eclinpath.com/

• Nationwide Specialist Laboratories. http://thehormonelab.com/

• Pineda M, Dooley MP. McDonald's Veterinary Endocrinology & Reproduction 5th Ed. 2002.

Wiley-BlackWell

• Prof. Dr. Erol ALAÇAM. Ders Notları (Teşekkürlerimle).

• Sözbilir Bayşu N, Bayşu N. 2008. Biyokimya. Güneş Tıp Kitapevleri, Ankara

• Voorbij AM et al. A contracted DNA repeat in LHX3 intron 5 is associated with aberrant

splicing and pituitary dwarfism in German shepherd dogs. PLoS One. 2011;6(11):e27940.

• Special thanks to Tanju BORATAŞ, B.Sc. for English translation of this document.

References

• Which of the following hormone has iodine in its structure?

a. Estradiol

b. Insulin

c. Thyroxin

d. ACTH

e. Secretin

Question 1

Answer: c

• Which of the following hormone stimulates development of

mammary glands and the secretion of milk?

a. Testosterone

b. Prolactin

c. Somatotropin

d. IGF-1

e. Insulin

Question 2

Answer: b

• Which of the following hormone has a role in the calcium

metabolism?

a. Thyroxin

b. Secretin

c. PTH

d. Glucagon

e. Cortisol

Question 3

Answer: c

Any Questions?

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Introduction to Metabolism

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