ENDOCRINOLOGY

1
ENDOCRINOLOGY

• For Biochemistry Diploma Students
• Faculty of Science
• Cairo University

2
(No Transcript)
3
Classical definition of a hormone

1. Chemical messengers
2. Synthesized by living cells and
3. Secreted by a specific gland
4. Secreted directly into the blood stream
5. Carried by the blood
6. Acts on a specific target
7. At a site distant from site of secretion
8. Secreted in minute quantities
9. Acts via specific receptors to exert specific
   actions

4
New Definition of a Hormone

• "Any substance released by a cell and which acts
  on another cell, near or far, regardless of the
  means of conveyance"

5
The seven principal glands and their hormones
Gland Hormone Type Chemical Group Major physiological role(s)
Hypothalamus Thyrotrophin-releasing hormone (TRH) Neurohormone Protein ? TSH secretion
Hypothalamus Somatostatin (SS) Neurohormone Protein ? GH secretion
Hypothalamus Gonadotrophin-releasing hormone (GnRH) Neurohormone Protein ? FSH LH secretion
Hypothalamus Corticotrophin-releasing hormone (CRH) Neurohormone Protein ? ACTH secretion
Hypothalamus Growth hormone-releasing hormone (GHRH) Neurohormone Protein ? GH secretion
Hypothalamus Prolactin releasing hormone Neurohormone Unknour ? Prolactin secretion
Hypothalamus 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
Anterior Pituitary Luteinizing hormone (LH) Endocrine Glycoprotein ? Female ovulationovarian estradiol progesterone synthesis ? Male testicular androgen synthesis
Anterior Pituitary Follicle-stimulating hormone (FSH) Endocrine Glycoprotein ? Female ovarian follicle growth estradiol synthesis ? Male spermatogenesis
Anterior Pituitary Prolactin Endocrine Protein ? Milk synthesis
Anterior Pituitary Growth hormone (GH) Endocrine Protein ? Hepatic somatomedin (IGF-I,II) biosynthesis
Anterior Pituitary Adrenocorticotrophin (ACTH) Endocrine Protein ? Adrenal steroidogenesis
6
Posterior Pituitary Vasopressin, antidiuretic hormone (VP, ADH) Endocrine Protein ? Renal water absorption vasoconstriction
Posterior Pituitary Oxytocin (OT) Endocrine Protein ? Milk secretion uterine contraction
Thyroid Thyroxine (T4) Tri-iodothyronine (T3) Endocrine Tyrosine-derived ? Growth differentiation calorigenesis (? metabolic rate oxygen consumption)
Thyroid 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
Adrenal Cortex 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
Adrenal Medulla Noradrenaline, Norepinephrine (NE) Endocrine Tyrosine-derived Response to stress
Pancreatic Islets Insulin Endocrine Protein ? Blood sugar ? protein, glycogen fat synthesis
Pancreatic Islets Glucagon Endocrine Protein ? Blood glucose gluconeogenesis glycogenolysis
Pancreatic Islets Somatostatin Paracrine Protein ? Secretion of pancreatic islets hormones
Pancreatic Islets Pancreatic polypeptide (PP) Paracrine Protein ? Secretion of pancreatic islets hormones bile
Gonads Ovary Testis Oestrogen Endocrine Steroid ? Female development, breasts, growth behavior
Gonads Ovary Testis Progesterone Endocrine Steroid ? Uterine mammary gland growth
Gonads Ovary Testis Testosterone Endocrine Steroid ? Male development growth of reproductive system
Gonads Ovary Testis Inhibin Endocrine Peptide ? FSH secretion
7
Some hormones secreted from tissues
Source Hormone Type Chemical group Major role
Stomach Gastrin Paracrine autocrine Protein ? gastric HCl secretion
Small Intestine Secretin Paracrine Protein ? pancreatic bicarbonate secretion
Small Intestine Cholecystokinin (CCK) autocrine Protein ? gall bladder contraction secretion of pancreatic enzymes
Small Intestine Gastric inhibitory hormone (GIP) Endocrine ? Gastric secretion, ? intestinal secretion, insulinotropic, anabolic hormone
Small Intestine Vasoactive intestinal peptide (VIP) Endocrine ? Intestinal secretion of water electrolytes relaxation of circulatory smooth muscles (vasodilator, hypotensive)
Small Intestine Motilin ? Contraction of stomach small intestine, stimulate gastric motor activity
Small Intestine Neurotensin (NT) Inhibits gastric acid secretion emptying of stomach
Small Intestine Substance P (SP) Contraction of gut smooth muscles, vasodilation
Small Intestine 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) Prostacyclins Thromboxanes Leukotrienes Autocrine paracrine Eicosanoid ? Second messenger formation. They have multiple effects blood clotting, muscle contraction, defense mechanism etc
8
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 bowel enhances glucose-mediated insulin relaese inhibits gastric acid secretion
Vasoactive intestinal peptide (VIP) pancreas smooth muscle relaxation stimulates pancreatic bicarbonate secretion
Motilin small bowel initiates interdigestive intestinal motility
Pancreatic polypeptide (PP) pancreas inhibits pancreatic bicarbonate and protein secretion
Enkephalins stomach, duodenum, gallbladder opiate-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
9
General 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)

10
Classification of hormones according to mode of
their delivery

1. Endocrine
2. Neuroendocrine
3. Paracrine
4. Autocrine
5. Luminal
6. Pheromone

11
(No Transcript)
12
Classification according to Chemical classes of
hormones

1. Protein and polypeptides
2. Steroids
3. Tyrosine-derived
4. Eicosanoids
5. Vitamins
6. Miscellaneous group Gaseous molecules (NO, CO),
   metabolic substances (glucose, lactic acid),
   chalones, lumones, pheromones

13
Polypeptide Hormone
14
Peptides
S
S
Cys
Try
Ile
Gln
Asn
Cys
Pro
Leu
Gly
15
Steroid Hormones
Estradiol
Testosterone
Cortisol
Pregnenolone
Progesterone
Aldosterone
16
Tyrosine-derived hormones
17
Eicosanoids
18
Vitamin D
19
Synthesis of Protein Hormones

• Transcription of a gene in the nucleus ? mRNA
• Translation of mRNA by ribosomes on RER ?
  pre-prohormone in ER
• Post-translational modification
• Pre-prohormone in ER ? prohormone by losing
  signal peptide sequence
• Prohormone migrates to Golgi complex ?
  incorporated into a vesicle
• prohormone in vesicle protease enzymes ? hormone

20
(No Transcript)
21
(No Transcript)
22
(No Transcript)
23
Synthesis of Steroid Hormones

• Activation of specific enzymes ? acetate ?
  cholesterol ? pregnenolone ? to the diff
  hormones.
• The SER, mitochondria and cytoplasm contain the
  enzymes required for the transformations

24
Steroids of the Adrenal Cortex
25
Synthesis of the male sex hormones
26
Synthesis of Vitamin D

• They are sterol hormones and have much in common
  to other steroid hormones
• Its precursor, cholecalciferol, is obtained from
  diet or synthesized by the ultraviolet
  irradiation of provitamin D in the skin
• Cholecalciferol, by a series of enzymes in the
  liver and kidney, is hydroxylated to the active
  hormone, calcitriol

27
Vitamin D
28
Synthesis of Tyrosine-derived hormones

• I.Thyroid hormones is a unique process
• Thyroid cells concentrate iodine
• Thyroid cells synthesize a glycoprotein,
  thyroglobulin
• Iodine is oxidized
• Iodine is oxidized, then coupled to iodotyrosine
  within thyroglobulin (organification process) by
  thyroid peroxidase enzyme
• Reuptake of thyroglobulin by endocytosis
• Proteolytic digestion by lysosomal enzymes
  (hydrolyases) ? T3 T4 (iodothyronines) and MIT
  DIT (iodotyrosines)
• II. Catecholamines They are synthesized from
  tyrosine by a number of enzymes in the cytoplasm
  and chromaffin granules

29
(No Transcript)
30
(No Transcript)
31
Synthesis of Catecholamines
32
Thyroid Hormone Synthesis
33
Synthesis of Eicosanoids

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

34
Pathways of Eicosanoids Synthesis
35
Storage

• Protein hormones In secretory granules within
  the cytoplasm
• Steroid hormones Are not stored. The hormones
  precursor, cholesterol esters, is the storage
  form
• Tyrosine-derived hormones
• Thyroid hormones in the thyroglobulin
• Catecholamines in secretory chromaffin granules
  in the cytoplasm ATP chromogranin
• Eicosanoids Are not stored.
• Vitamin D Cholecalciferol is stored in adipose
  tissue. Liver stores its metabolite

36
Release

• Protein hormones By exocytosis
• Steroid hormones by diffusion immediately upon
  synthesis
• Vitamin D by diffusion immediately upon
  synthesis
• Tyrosine derived hormones
• Thyroid hormones fusion of lysosomes with
  colloid droplets, the hormones are released by
  exocytosis from the basement membrane
• Catecholamines stimulus-secretion coupling
  requiring Ca, vesicular exocytosis
• Eicosanoids by diffusion

37
Transport

• Protein hormones mostly unbound, free in the
  blood
• Steroid hormones Bound to a plasma protein
  (high- affinity binding to globulin and
  low-affinity to albumin). Cortisol to
  transcortin, sex hormones to sex-hormone-binding
  globulin (SHBG).
• Vitamin D Bound to a globulin (transcalciferin)
• Tyrosine-derived hormone
• Thyroid hormones Mostly bound to
  thyronine-binding globulin (TBG) or prealbumin
  (transthyretin)
• Catecholamines Bound to albumin.
• Eicosanoids Are not transported. They act as
  autocrine or paracrine hormones

38
Purpose of binding of hormones to proteins

1. The hormone is protected from the inactivating
   systems present in the blood.
2. The hormone is maintained in a stored
   circulating form to be readily available to its
   target tissues.
3. Ensure ubiquitous distribution of the
   water-insoluble hormones.

39
Relation between bound and unbound hormone

• A dynamic equilibrium exists between the
  concentrations of free (unbound) hormone, plasma
  protein, and the hormone-protein complex
• HxP HP
• HxP
• K
• Where K is the dissociation constant

HP
40
Peripheral Conversion

• Some biologically active hormones are converted
  to other equally active hormones in peripheral
  tissues such as liver, breast adipose tissue,
  brain etc
• Example
• Testosterone dihydrotestosterone
• Thyroxine (T4) triiodothyronine (T3)

41

• Single hormone, different effects.
• Example
• Estradiol acts on ovarian follicles to promote
  granulosa cell differentiation, on uterus to
  stimulate its growth and maintain the cyclic
  change of uterine mucosa, on mammary gland to
  stimulate ductal growth, on bone to promote
  linear growth and closure of epiphyseal plates,
  on HPA to regulate secretion of gonadotropins and
  prolactin, on metabolic processes to affect
  adipose tissue distribution, volume of ECF, etc
• Several hormones, single function.
• Example
• Release of fatty acids (lipolysis) from adipose
  tissue stimulated by catecholamines, glucagon,
  secretin, prolactin and B-lipotropin

42
Permissive effect of Hormones

• It is the effect that some hormones exhibit,
  these hormones have little effect by themselves,
  but when they are present they affect other
  hormones to become fully manifested.
• Example
• Development of mammary gland, under infleunce of
  prolactin, estradiol progesterone and the
  permissive influence of glucocorticoids, thyroid
  hormones and insulin