Download Thyroid hormones

ENDOCRINOLOGY
For Biochemistry Diploma
Students
Faculty of Science
Cairo University
Classical definition of a hormone
1.
2.
3.
4.
5.
6.
7.
8.
9.
Chemical messengers
Synthesized by living cells and
Secreted by a specific gland
Secreted directly into the blood stream
Carried by the blood
Acts on a specific target
At a site distant from site of secretion
Secreted in minute quantities
Acts via specific receptors to exert specific
actions
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"
The seven principal glands and their hormones
Gland
Hypothalamu
s
Hormone
Thyrotrophin-releasing
(TRH)
Type
hormone
Somatostatin (SS)
Major physiological role(s)
Neurohormone
Protein
↑ TSH secretion
Neurohormone
Protein
↓ GH secretion
Gonadotrophin-releasing
(GnRH)
hormone
Neurohormone
Protein
↑ FSH & LH secretion
Corticotrophin-releasing
(CRH)
hormone
Neurohormone
Protein
↑ ACTH secretion
Growth hormone-releasing hormone
(GHRH)
Neurohormone
Protein
↑ GH secretion
Prolactin releasing hormone
Neurohormone
Unknour
↑ Prolactin secretion
Neurohormone
Tyrosinederived
↓ Prolactin secretion
Thyroid stimulating hormone (TSH)
Endocrine
Glycoprotein
↑ Thyroid hormones (T4 & T3) synthesis and
secretion
Luteinizing hormone (LH)
Endocrine
Glycoprotein
↑
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
Prolactin-inhibiting
Dopamine (PIH)
Anterior
Pituitary
Chemical
Group
hormone,
Female: ovulation;ovarian estradiol
progesterone synthesis
↑ Male: testicular androgen synthesis
&
Vasopressin, antidiuretic hormone (VP,
ADH)
Endocrine
Protein
↑ Renal water absorption; vasoconstriction
Oxytocin (OT)
Endocrine
Protein
↑ Milk secretion; uterine contraction
Thyroxine (T4) & Tri-iodothyronine (T3)
Endocrine
Tyrosinederi
ved
↑ Growth; differentiation; calorigenesis (↑ metabolic
rate & oxygen consumption)
Calcitonin (CT)
Endocrine
Protein
↓ Blood Ca2+
Parathyro
id
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
Med
ulla
Adrenaline, Epinephrine (E)
Endocrine
Tyrosinederi
ved
Multiple effects on nerves, muscles, cellular secretions
& metabolism; cardiovascular function; response
to stress
Noradrenaline, Norepinephrine (NE)
Endocrine
Tyrosinederi
ved
Response to stress
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
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
Posterior
Pituitary
Thyroid
Pancreatic
Islets
Gonads
Ovary
Testis
Some hormones secreted from tissues
Source
Hormone
Type
Chemical
group
Major role
Stomach
Gastrin
Paracrine &
autocrin
e
Protein
↑ gastric HCl secretion
Small
Intestin
e
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)
Prostacyclins
Thromboxanes
Leukotrienes
Autocrine &
paracrin
e
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 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
General functions of hormones
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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
according to mode of their delivery
1.
2.
3.
4.
5.
6.
Endocrine:
Neuroendocrine:
Paracrine:
Autocrine:
Luminal:
Pheromone
Classification according to
Chemical classes of hormones
1.
2.
3.
4.
5.
6.
Protein and polypeptides
Steroids
Tyrosine-derived
Eicosanoids
Vitamins
Miscellaneous group: Gaseous molecules
(NO, CO), metabolic substances (glucose,
lactic acid), chalones, lumones,
pheromones
Polypeptide Hormone
Peptides
S
S
Cys
Try
Ile
Gln
Asn
Cys
Pro
Leu
Gly
Steroid Hormones
Testosterone
Aldosterone
Estradiol
Pregnenolone:
Cortisol
Progesterone
Tyrosine-derived hormones
Eicosanoids
Vitamin D
Synthesis of Protein Hormones
Transcription of a gene in the nucleus 
mRNA
2. Translation of mRNA by ribosomes on RER
 pre-prohormone in ER
3. Post-translational modification:
I. Pre-prohormone in ER  prohormone
by losing signal peptide sequence
II. Prohormone migrates to Golgi complex
 incorporated into a vesicle
III.prohormone in vesicle + protease
enzymes  hormone
1.
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
Steroids of the Adrenal Cortex
Synthesis of the male sex
hormones
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
Vitamin D
Synthesis of Tyrosine-derived
hormones
I.Thyroid hormones: is a unique process
1. Thyroid cells concentrate iodine
2. Thyroid cells synthesize a glycoprotein,
thyroglobulin
3. Iodine is oxidized
4. Iodine is oxidized, then coupled to
iodotyrosine within thyroglobulin
(organification process) by thyroid
peroxidase enzyme
5. Reuptake of thyroglobulin by endocytosis
6. 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
Synthesis of Catecholamines
Thyroid Hormone Synthesis
Synthesis of Eicosanoids
From fatty acid (arachidonic acid)
released from phospholipids in cell
membrane by means of a number of
enzymes.
Pathways of Eicosanoids Synthesis
Storage
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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.
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Vitamin D: Cholecalciferol is stored in adipose
tissue. Liver stores its metabolite
Release
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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
Transport
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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
Purpose of binding of hormones to
proteins:
1.
2.
3.
The hormone is protected from the
inactivating systems present in the
blood.
The hormone is maintained in a
“stored” circulating form to be readily
available to its target tissues.
Ensure ubiquitous distribution of the
water-insoluble hormones.
Relation between bound and
unbound hormone
A dynamic equilibrium exists between
the concentrations of free (unbound)
hormone, plasma protein, and the
hormone-protein complex:
[H]x[P]
[HP]
[H]x[P]
= K
[HP]
Where K is the dissociation constant
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)

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
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
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