endocrinology for biochemistry diploma students faculty of science cairo university
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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
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