ENDOCRINOLOGYENDOCRINOLOGY

For Biochemistry Diploma For Biochemistry Diploma StudentsStudents

Faculty of ScienceFaculty of Science

Cairo UniversityCairo University

Classical definition of a hormoneClassical definition of a hormone

1.1. Chemical messengers Chemical messengers

2.2. Synthesized by living cells and Synthesized by living cells and

3.3. Secreted by a specific glandSecreted by a specific gland

4.4. Secreted directly into the blood streamSecreted directly into the blood stream

5.5. Carried by the bloodCarried by the blood

6.6. Acts on a specific target Acts on a specific target

7.7. At a site distant from site of secretionAt a site distant from site of secretion

8.8. Secreted in minute quantitiesSecreted in minute quantities

9.9. Acts via specific receptors to exert specific Acts via specific receptors to exert specific actionsactions

New Definition of a HormoneNew Definition of a Hormone

"Any substance "Any substance released by a cell and released by a cell and which acts on another which acts on another

cell, near or far, cell, near or far, regardless of the regardless of the

means of conveyance" means of conveyance"

The seven principal glands and their hormonesThe seven principal glands and their hormones

Gland Hormone Type Chemical Group

Major physiological role(s)

Hypothalamus

Thyrotrophin-releasing hormone (TRH)

Neurohormone Protein ↑ TSH secretion

Somatostatin (SS) Neurohormone Protein ↓ GH secretion

Gonadotrophin-releasing hormone (GnRH)

Neurohormone Protein ↑ FSH & LH secretion

Corticotrophin-releasing hormone (CRH)

Neurohormone Protein ↑ ACTH secretion

Growth hormone-releasing hormone (GHRH)

Neurohormone Protein ↑ GH secretion

Prolactin releasing hormone Neurohormone Unknour ↑ Prolactin secretion

Prolactin-inhibiting hormone, Dopamine (PIH)

Neurohormone Tyrosine-derived

↓ Prolactin secretion

Anterior Pituitary

Thyroid stimulating hormone (TSH) Endocrine Glycoprotein ↑ Thyroid hormones (T4 & T3) synthesis and

secretion

Luteinizing hormone (LH) Endocrine Glycoprotein ↑ Female: ovulation;ovarian estradiol & progesterone synthesis

↑ Male: testicular androgen synthesis

Follicle-stimulating hormone (FSH) Endocrine Glycoprotein ↑ Female: ovarian follicle growth; estradiol synthesis

↑ Male: spermatogenesis

Prolactin Endocrine Protein ↑ Milk synthesis;

Growth hormone (GH) Endocrine Protein ↑ Hepatic somatomedin (IGF-I,II) biosynthesis

Adrenocorticotrophin (ACTH) Endocrine Protein ↑ Adrenal steroidogenesis

PosteriorPituitary

Vasopressin, antidiuretic hormone (VP, ADH)

Endocrine Protein ↑ Renal water absorption; vasoconstriction

Oxytocin (OT) Endocrine Protein ↑ Milk secretion; uterine contraction

Thyroid Thyroxine (T4) & Tri-iodothyronine (T3) Endocrine Tyrosine-derived

↑ Growth; differentiation; calorigenesis (↑ metabolic rate & oxygen consumption)

Calcitonin (CT) Endocrine Protein ↓ Blood Ca2+

Parathyroid

Parathyroid hormone (PTH) Endocrine Protein ↑ Blood calcium (Ca2+), ↓ Blood phosphate (PO4-3)

Adrenal Cortex

Aldosterone Endocrine Steroid ↑ Sodium retention

Cortisol Endocrine Steroid ↑ Carbohydrate metabolism;

Adrenal Medulla

Adrenaline, Epinephrine (E) Endocrine Tyrosine-derived

Multiple effects on nerves, muscles, cellular secretions & metabolism; cardiovascular function; response

to stress

Noradrenaline, Norepinephrine (NE) Endocrine Tyrosine-derived

Response to stress

Pancreatic Islets

Insulin Endocrine Protein ↓ Blood sugar; ↑ protein, glycogen & fat synthesis

Glucagon Endocrine Protein ↑ Blood glucose; gluconeogenesis; glycogenolysis

Somatostatin Paracrine Protein ↓ Secretion of pancreatic islets hormones

Pancreatic polypeptide (PP) Paracrine Protein ↓ Secretion of pancreatic islets hormones & bile

GonadsOvaryTestis

Oestrogen Endocrine Steroid ↑ Female development, breasts, growth & behavior

Progesterone Endocrine Steroid ↑ Uterine & mammary gland growth

Testosterone Endocrine Steroid ↑ Male development & growth of reproductive system

Inhibin Endocrine Peptide ↓ FSH secretion

Some hormones secreted from tissuesSome hormones secreted from tissues Source Hormone Type Chemical

groupMajor role

Stomach Gastrin Paracrine & autocrine

Protein ↑ gastric HCl secretion

Small Intestine

Secretin Paracrine & Protein ↑ pancreatic bicarbonate secretion

Cholecystokinin (CCK) autocrine Protein ↑ gall bladder contraction & secretion of pancreatic enzymes

Gastric inhibitory hormone (GIP) Endocrine ↓ Gastric secretion, ↑ intestinal secretion, insulinotropic, anabolic hormone

Vasoactive intestinal peptide (VIP) Endocrine ↑ Intestinal secretion of water & electrolytes; relaxation of circulatory smooth muscles (vasodilator, hypotensive)

Motilin ↑ Contraction of stomach & small intestine, stimulate gastric motor activity

Neurotensin (NT) Inhibits gastric acid secretion & emptying of stomach

Substance P (SP) Contraction of gut smooth muscles, vasodilation

Gastrin releasing peptide (GRP) ↑ release gastrin

Heart Atrial Natriuretic peptide (ANP) Endocrine Protein ↑ renal salt excretion, GFR & urine volume; lowering of blood pressure

Kidney Vitamin D3 Endocrine Steroid ↑ calcium absorption by the intestine

Most Tissues Prostaglandins(PGs)ProstacyclinsThromboxanesLeukotrienes

Autocrine & paracrine

Eicosanoid ↑ Second messenger formation. They have multiple effects; blood clotting, muscle contraction, defense mechanism etc

Gastrointestinal (luminal) Hormones

Hormone Location Major Action

Gastrin gastric antrum, duodenum gastric acid and pepsin secretion

Cholecystokinin (CCK) duodenum, jejunum pancreatic amylase secretion

Secretin duodenum, jejunum pancreatic bicarbonate secretion

Gastric inhibitory peptide (GIP) small bowelenhances glucose-mediated insulin relaese; inhibits gastric

acid secretion

Vasoactive intestinal peptide (VIP)

pancreassmooth muscle relaxation; stimulates pancreatic bicarbonate

secretion

Motilin small bowel initiates interdigestive intestinal motility

Pancreatic polypeptide (PP) pancreas inhibits pancreatic bicarbonate and protein secretion

Enkephalinsstomach, duodenum,

gallbladderopiate-like actions

Substance P entire gastrointestinal tract physiological actions uncertain

Bombesin-like immunoreactivity (BLI)

stomach, duodenum stimulates release of gastrin and CCK

Neurotensin ileum physiological actions unknown

Enteroglucagon pancreas, small intestine physiological actions unknown

General functions of hormonesGeneral functions of hormones Control Reproductive processes: differentiation,

maturation, gametogenesis. Growth and development: stimulate or inhibit

cellular proliferation Homeostasis: Maintenance of healthy internal

environment in a continuously changing external and internal environments

Metabolism: anabolic and catabolic processes, muscular activity, excretion, reabsorption of ions

Energy production, utilization and storage Animal behavior: sexual, aggressive and maternal Other hormones (synthesis, secretion, permissive

action)

Classification of hormones Classification of hormones according to mode of their deliveryaccording to mode of their delivery

1.1. Endocrine:Endocrine:

2.2. Neuroendocrine:Neuroendocrine:

3.3. Paracrine:Paracrine:

4.4. Autocrine:Autocrine:

5.5. Luminal:Luminal:

6.6. PheromonePheromone

Classification according toClassification according to Chemical classes of hormonesChemical classes of hormones 1.1. Protein and polypeptidesProtein and polypeptides

2.2. SteroidsSteroids

3.3. Tyrosine-derivedTyrosine-derived

4.4. EicosanoidsEicosanoids

5.5. VitaminsVitamins

6.6. Miscellaneous group: Gaseous molecules Miscellaneous group: Gaseous molecules (NO, CO), metabolic substances (glucose, (NO, CO), metabolic substances (glucose, lactic acid), chalones, lumones, lactic acid), chalones, lumones, pheromones pheromones

Polypeptide HormonePolypeptide Hormone

PeptidesPeptides

Cys Try Ile Gln Asn Cys Pro Leu Gly

S S

Pregnenolone : Progesterone Aldosterone

Testosterone Estradiol Cortisol

Steroid Hormones

Tyrosine-derived hormonesTyrosine-derived hormones

EicosanoidsEicosanoids

Vitamin DVitamin D

Synthesis of Protein HormonesSynthesis of Protein Hormones

1.1. TranscriptionTranscription of a gene in the nucleus of a gene in the nucleus mRNA mRNA

2.2. TranslationTranslation of mRNA by ribosomes on RER of mRNA by ribosomes on RER pre-prohormone in ER pre-prohormone in ER

3.3. Post-translational modificationPost-translational modification::I.I. Pre-prohormone in ER Pre-prohormone in ER prohormone prohormone

by losing signal peptide sequence by losing signal peptide sequence II.II. Prohormone migrates to Golgi complex Prohormone migrates to Golgi complex

incorporated into a vesicle incorporated into a vesicleIII.III. prohormone in vesicle + protease prohormone in vesicle + protease

enzymes enzymes hormone hormone

Activation of specific enzymes: Activation of specific enzymes: acetate acetate cholesterol cholesterol pregnenolone pregnenolone to the diff to the diff hormoneshormones..

The SER, mitochondria and cytoplasm The SER, mitochondria and cytoplasm contain the enzymes required for the contain the enzymes required for the transformations transformations

Synthesis of Steroid HormonesSynthesis of Steroid Hormones

Steroids of the Adrenal CortexSteroids of the Adrenal Cortex

Synthesis of the male sex Synthesis of the male sex hormones hormones

They are sterol hormones and have They are sterol hormones and have much in common to other steroid much in common to other steroid hormoneshormones

Its precursor, Its precursor, cholecalciferolcholecalciferol, is , is obtained from diet or synthesized by obtained from diet or synthesized by the ultraviolet irradiation of the ultraviolet irradiation of provitamin D in the skinprovitamin D in the skin

Cholecalciferol, by a series of enzymes Cholecalciferol, by a series of enzymes in the liver and kidney, is in the liver and kidney, is hydroxylated to the active hormonehydroxylated to the active hormone, , calcitriolcalcitriol

Synthesis of VitaminSynthesis of Vitamin DD

Vitamin DVitamin D

Synthesis of Tyrosine-derived Synthesis of Tyrosine-derived hormoneshormones

I.I.Thyroid hormonesThyroid hormones: : is a unique processis a unique process1.1. Thyroid cells concentrate iodineThyroid cells concentrate iodine2.2. Thyroid cells synthesize a glycoprotein, Thyroid cells synthesize a glycoprotein,

thyroglobulinthyroglobulin3.3. Iodine is oxidizedIodine is oxidized4.4. Iodine is oxidized, then coupled to Iodine is oxidized, then coupled to

iodotyrosine within thyroglobulin iodotyrosine within thyroglobulin (organification process) by thyroid peroxidase (organification process) by thyroid peroxidase enzymeenzyme

5.5. Reuptake of thyroglobulin by endocytosis Reuptake of thyroglobulin by endocytosis 6.6. Proteolytic digestion by lysosomal enzymes Proteolytic digestion by lysosomal enzymes

(hydrolyases) (hydrolyases) T 3+ T4 (iodothyronines) and T 3+ T4 (iodothyronines) and MIT+ DIT (iodotyrosines)MIT+ DIT (iodotyrosines)

II.II. Catecholamines Catecholamines: : They are synthesized from They are synthesized from tyrosine by a number of enzymes in the tyrosine by a number of enzymes in the cytoplasm and chromaffin granules cytoplasm and chromaffin granules

Synthesis of CatecholaminesSynthesis of Catecholamines

Thyroid Hormone SynthesisThyroid Hormone Synthesis

Synthesis of EicosanoidsSynthesis of Eicosanoids

From fatty acid (arachidonic acid) From fatty acid (arachidonic acid) released from phospholipids in cell released from phospholipids in cell membrane by means of a number of membrane by means of a number of enzymes.enzymes.

Pathways of Eicosanoids SynthesisPathways of Eicosanoids Synthesis

StorageStorage Protein hormones: Protein hormones: In secretory granules within In secretory granules within

the cytoplasmthe cytoplasm Steroid hormones: Steroid hormones: Are not stored. The Are not stored. The

hormones precursor, cholesterol esters, is the hormones precursor, cholesterol esters, is the storage formstorage form

Tyrosine-derived hormonesTyrosine-derived hormones Thyroid hormones: in the thyroglobulinThyroid hormones: in the thyroglobulin Catecholamines: in secretory chromaffin granules Catecholamines: in secretory chromaffin granules

in the cytoplasm + ATP + chromograninin the cytoplasm + ATP + chromogranin• Eicosanoids:Eicosanoids: Are not stored. Are not stored.

Vitamin DVitamin D: Cholecalciferol is stored in adipose : Cholecalciferol is stored in adipose tissue. Liver stores its metabolite tissue. Liver stores its metabolite

ReleaseRelease Protein hormones: Protein hormones: ByBy exocytosisexocytosis Steroid hormones: Steroid hormones: by diffusion by diffusion

immediately upon synthesisimmediately upon synthesis Vitamin D: Vitamin D: by diffusion immediately upon by diffusion immediately upon

synthesissynthesis Tyrosine – derived hormones:Tyrosine – derived hormones: Thyroid hormones: fusion of lysosomes Thyroid hormones: fusion of lysosomes

with colloid droplets, the hormones are with colloid droplets, the hormones are released by exocytosis from the basement released by exocytosis from the basement membrane membrane

Catecholamines: stimulus-secretion Catecholamines: stimulus-secretion coupling requiring Ca, vesicular exocytosiscoupling requiring Ca, vesicular exocytosis

Eicosanoids: Eicosanoids: by diffusionby diffusion

TransportTransport Protein hormones: Protein hormones: mostly unbound, free in the mostly unbound, free in the

bloodblood Steroid hormones: Steroid hormones: Bound to a plasma protein Bound to a plasma protein

(high- affinity binding to globulin and low-affinity (high- affinity binding to globulin and low-affinity to albumin). Cortisol to transcortin, sex hormones to albumin). Cortisol to transcortin, sex hormones to sex-hormone-binding globulin (SHBG).to sex-hormone-binding globulin (SHBG).

Vitamin D: Vitamin D: Bound to a globulin (transcalciferin)Bound to a globulin (transcalciferin) Tyrosine-derived hormone:Tyrosine-derived hormone:

• Thyroid hormones: Mostly Thyroid hormones: Mostly bound to bound to thyronine-binding globulin (TBG) or prealbumin thyronine-binding globulin (TBG) or prealbumin (transthyretin)(transthyretin)

• Catecholamines:Catecholamines: Bound to albumin Bound to albumin.. Eicosanoids: Eicosanoids: Are not transported. They act as Are not transported. They act as

autocrine or paracrine hormonesautocrine or paracrine hormones

Purpose of binding of hormones to Purpose of binding of hormones to proteins:proteins:

1.1. The hormone is protected from the The hormone is protected from the inactivating systems present in the inactivating systems present in the blood.blood.

2.2. The hormone is maintained in a The hormone is maintained in a “stored” circulating form to be readily “stored” circulating form to be readily available to its target tissues.available to its target tissues.

3.3. Ensure ubiquitous distribution of the Ensure ubiquitous distribution of the water-insoluble hormones. water-insoluble hormones.

Relation between bound and Relation between bound and unbound hormoneunbound hormone

A dynamic equilibrium exists between A dynamic equilibrium exists between the concentrations of free (unbound) the concentrations of free (unbound) hormone, plasma protein, and the hormone, plasma protein, and the hormone-protein complex:hormone-protein complex:

[H]x[P] [HP][H]x[P] [HP]

[H]x[P][H]x[P]

= K = K

Where K is the dissociation constantWhere K is the dissociation constant

[HP][HP]

Peripheral ConversionPeripheral Conversion

Some biologically active hormones are Some biologically active hormones are converted to other equally active converted to other equally active hormones in peripheral tissues such as hormones in peripheral tissues such as liver, breast adipose tissue, brain etcliver, breast adipose tissue, brain etc

Example:Example:

Testosterone dihydrotestosterone Testosterone dihydrotestosterone

Thyroxine (TThyroxine (T44) triiodothyronine (T) triiodothyronine (T33))

Single hormone, different effectsSingle hormone, different effects..Example:Example:Estradiol acts on ovarian follicles to promote Estradiol acts on ovarian follicles to promote

granulosa cell differentiation, on uterus to granulosa cell differentiation, on uterus to stimulate its growth and maintain the cyclic stimulate its growth and maintain the cyclic change of uterine mucosa, on mammary gland to change of uterine mucosa, on mammary gland to stimulate ductal growth, on bone to promote stimulate ductal growth, on bone to promote linear growth and closure of epiphyseal plates, on linear growth and closure of epiphyseal plates, on HPA to regulate secretion of gonadotropins and HPA to regulate secretion of gonadotropins and prolactin, on metabolic processes to affect prolactin, on metabolic processes to affect adipose tissue distribution, volume of ECF, etc adipose tissue distribution, volume of ECF, etc

Several hormones, single functionSeveral hormones, single function..Example:Example:Release of fatty acids (lipolysis) from adipose tissue Release of fatty acids (lipolysis) from adipose tissue

stimulated by catecholamines, glucagon, secretin, stimulated by catecholamines, glucagon, secretin, prolactin and B-lipotropinprolactin and B-lipotropin

Permissive effect of HormonesPermissive effect of Hormones

It is the effect that some hormones It is the effect that some hormones exhibit, these hormones have little exhibit, these hormones have little effect by themselves, but when they effect by themselves, but when they are present they affect other hormones are present they affect other hormones to become fully manifested.to become fully manifested.

Example:Example:Development of mammary gland, under Development of mammary gland, under

infleunce of prolactin, estradiol & infleunce of prolactin, estradiol & progesterone and the permissive progesterone and the permissive influence of glucocorticoids, thyroid influence of glucocorticoids, thyroid hormones and insulinhormones and insulin