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Thyroid gland
The synthesis and release of thyroid
hormone involves a number of steps
1. Uptake of iodide (ATP-dependent Na+, K+ATPase).
2. Activation and Organification of lodide
(catalyzed by thyroperoxidase).
3. Coupling Reaction and Storage as Colloid
(Iodide peroxidase or a "coupling enzyme"
catalyzes the "coupling reaction).
4. Processing of TG and Release of Thyroid
Hormone.
Biological Actions of Thyroid
Hormones
Type
bound to thyroxine-binding globulin (TBG)
bound to transthyretin or "thyroxinebinding prealbumin" (TTR or TBPA)
albumin
unbound T4 (fT4)
unbound T3 (fT3)
Percent
70%
10-15%
15-20%
0.03%
0.3%
Cardiovascular System
Thyroid hormone enhances cardiac
contractility and exerts a positive
chronotropic effect on the heart,
increasing heart rate by a mechanism that
may involve more than a potentiation of
the β-adrenergic effect.
Intermediary Metabolism
Thyroid hormone increases both lipolysis and
lipogenesis, although lipogenesis is stimulated
before lipolysis, due to early induction of malic
enzyme (malate dehydrogenase), glucose-6phosphate dehydrogenase, and fatty acid synthase.
Thyroid hormone lowers serum cholesterol levels.
In liver, kidney, skeletal muscle, cardiac muscle, and
adipose tissue, thyroid hormone stimulates Na+,K+ATPase gene expression and promotes
thermogenesis.
Growth and Maturation
Thyroid hormone stimulates production of IGF-I
directly (liver) and indirectly (via increased
growth hormone, GH).
Reproductive System
Thyroid hormone increases total plasma androgen
levels by increasing the production of testosteronebinding globulin (TeBG) by the liver.
Video
Thyroid Hormone Synthesis
Vedieo
Human Physiology - Thyroid
Hormone Feedback and Function
Calcitonin
Calcitonin (also known as thyrocalcitonin)
is a 32-amino acid linear polypeptide
hormone that is produced in humans
primarily by the parafollicular cells (also
known as C-cells) of the thyroid.
It acts to reduce blood calcium (Ca2+),
opposing the effects of parathyroid
hormone (PTH).
More specifically, calcitonin lowers blood Ca2+
levels in two ways:
Major effect: Inhibits osteoclast activity in bones
Minor effect: Inhibits renal tubular cell
reabsorption of Ca2+ and phosphate, allowing
them to be excreted in the urine.
The calcitonin receptor, found on osteoclasts,
and in the kidney and regions of the brain, is a G
protein-coupled receptor, which is coupled by
Gs to adenylate cyclase and thereby to the
generation of cAMP in target cells.
Parathyroid gland
Parathyroid hormone
Parathyroid
hormone
parathyroid chief cells.
secreted
by
Calcium:
1. Stimulates calcium release from bone,
thereby increasing blood calcium
2. Stimulates osteoclasts, thus breaking
down bone.
3. Stimulates calcium reabsorption in
kidney
4. Stimulates activated vitamin D
production in kidney
Phosphate:
1. Stimulates Phosphate release from
bones, thereby increasing blood
Phosphate.
2. Inhibits Phosphate reabsorption in
kidney, so more Phosphate excreted
Overall, small net drop in serum
Phosphate.
Reproductive Hormones
Testosterone
Testosterone in plasma exists in two
fractions: TeBG bound (44%) and nonTeBG-bound (56%).
Biological Effects of Androgens
The biological effects of androgenic hormones
can be of two types:
Reproductive (androgenic), i.e., promoting the
primary and secondary sexual characteristics of
a male.
Non-reproductive, which includes anabolic
effects.
Reproductive (Androgenic) Effects
1. Testes
At puberty, locally produced testosterone promotes
spermatogenesis in the seminiferous tubules,
although it is not known with certainty whether or
not the Sertoli cells contain 5α-reductase.
2. Internal and External Genitalia
In the fetus, testosterone causes differentiation of the
Wolffian ducts into the male-type reproductive tract, and
thereby rescues the tissue from pre-programmed destruction.
The seminal vesicles, which differentiate from the Wolffian
duct as a result of testosterone action, produce 5α-reductase2 from week 13-14 and become DHT-responsive after that;
thus, development and function (but not appearance), may be
regulated by DHT from the second trimester through
adulthood.
At puberty, however, the derivative of the genital tubercle
(clitoris and penis) becomes responsive to testosterone, which
enhances the male-type morphology by promoting growth of
the existing structure.
3. Skin
The hair follicles and sebaceous glands in the androgen
sensitive areas of the skin and sebaceous glands
throughout the body contain 5α-reductase type 1 and
respond to DHT.
At puberty, DHT stimulates the appearance and growth
of terminal hair in certain androgen-sensitive regions of
the body (face, chest, upper pubic triangle, nostrils,
external ear).
DHT stimulates the growth and secretory function
(sebum production) of all sebaceous glands, and thus
predisposes the skin to acne formation.
Male pattern baldness
4. Voice Pitch
Testosterone promotes enlargement of the larynx and
thickening of the vocal folds (vocal cords), causing a
lowering of the voice pitch.
Non-reproductive Effects
1. Skeletal Muscle
Testosterone promotes skeletal muscle growth by
stimulating both hypertrophy and mitosis of
myofibrils and increases the fast-twitch isoform of
myosin heavy chain.
The extent to which skeletal muscle mass can be
increased is limited by the concentration of androgen
receptors in the muscle that can be activated.
.
2. Bone
Androgens promote skeletal growth and maturation by a
direct effect on bone tissue and by an indirect effect on
growth hormone (GH) release.
At puberty, the increasing levels of androgens stimulate
the release of GH and result in accelerated endochondral
growth of the epiphyses of long bones, which causes a
doubling of height gain that is maximal at about mid- to
late puberty.
3. Blood Volume
Testosterone acts on the proximal tubule of
the nephron to promote the reabsorption of
K+, Na+, and Cl-, which, along with stimulated
erythropoiesis, contributes to the androgenassociated increase in blood volume.
4. Erythropoiesis
Androgens stimulate the production of
erythropoietin by the kidney and, in part, cause an
increase in hematocrit by this mechanism.
This may explain why males have a higher hematocrit
than females.
5. Adipose Tissue
Androgens promote truncal-abdominal fat deposition and
favor development of upper body obesity.
6. Liver
Androgens cause a reduction in the plasma levels
of testosterone-estradiol-binding globulin (TeBG),
which results in an increased percentage of
testosterone that is accessible for tissue uptake.
Estrogen
Estrogens are a group of compounds named for
their importance in the estrous cycle of humans
and other animals.
Their name comes from the Greek words estrus
= sexual desire and gen = to generate.
The three major naturally occurring
estrogens in women are estrone (E1),
estradiol (E2), and estriol (E3).
Estrone is produced during menopause,
estradiol is the predominant form in
nonpregnant females, and estriol is the
primary estrogen of pregnancy.
Structural function
Promote formation of female secondary sex
characteristics
Accelerate metabolism
Reduce muscle mass
Increase fat stores
Stimulate endometrial growth
Increase uterine growth
Increase vaginal lubrication
Thicken the vaginal wall
Maintenance of vessel and skin
Reduce bone resorption, increase bone formation.
Protein synthesis
Increase hepatic production of binding proteins.
Coagulation
Increase circulating level of factors 2, 7, 9, 10, plasminogen.
Decrease antithrombin III.
Increase platelet adhesiveness.
Lipid
Increase HDL, triacylglycerol
Decrease LDL, fat deposition
Progesterone
Progesterone also known as P4 (pregn-4-ene3,20-dione) is a C-21 steroid hormone involved
in the female menstrual cycle, pregnancy
(supports gestation) and embryogenesis of
humans and other species.
Progesterone is sometimes called the
"hormone of pregnancy", and it has many
roles relating to the development of the fetus:
Progesterone has key effects via non-genomic
signalling on human sperm as they migrate through
the female tract before fertilization occurs, though
the receptor(s) as yet remain unidentified.
Since eggs release progesterone, sperm may use
progesterone as a homing signal to swim toward
eggs.
During implantation and gestation,
progesterone appears to decrease the
maternal immune response to allow
for the acceptance of the pregnancy.
Pancreatic hormones
The pancreas is a glandular organ in the digestive
system and endocrine system of vertebrates.
It is an endocrine gland producing several
important hormones including insulin,
glucagon, somatostatin, and pancreatic
polypeptide which circulate in the blood.
Insulin
Proinsulin is the prohormone precursor
to insulin made in the beta cells of the islets of
Langerhans, specialized regions of the pancreas.
Proinsulin is synthesized in the endoplasmic
reticulum, where it is folded and its disulfide
bonds are oxidized. It is then transported to
the Golgi apparatus where it is packaged into
secretory vesicles, and where it is processed by
a series of proteases to form mature insulin.
Mature insulin has 35 fewer amino acids; 4
are removed altogether, and the remaining
31 form the C-peptide.
The C-peptide is abstracted from the center
of the proinsulin sequence; the two other
ends (the B chain and A chain) remain
connected by disulfide bonds.
Increased glycogen synthesis.
Increased lipid synthesis.
Increased esterification of fatty acids – forces
adipose tissue to make fats (i.e., triglycerides) from
fatty acid esters.
Decreased proteolysis
Decreased lipolysis
Decreased gluconeogenesis
Increased amino acid uptake – forces cells to
absorbe circulating amino acids; lack of insulin
inhibits absorption.
Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1),
which starts many protein activation cascades (2). These include translocation of Glut4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis
(4), glycolysis (5) and triacylglycerol (6).
Glucagon
Glucagon, a peptide hormone secreted by
the pancreas, raises blood glucose levels.
The pancreas releases glucagon when blood
sugar (glucose) levels fall too low. Glucagon causes
the liver to convert stored glycogen into glucose,
which is released into the bloodstream.
Glucagon is a 29-amino acid polypeptide.
Glucagon is generated from the cleavage
of proglucagon secreted by pancreatic islet α
cells.
Glucagon generally elevates the amount
of glucose in the blood by
promoting gluconeogenesis and glycogenolysis.
Glucose is stored in the liver in the form of
glycogen, which is a polymer made up of glucose
molecules.
Liver cells (hepatocytes) have glucagon
receptors. When glucagon binds to the glucagon
receptors, the liver cells convert the glycogen
polymer into individual glucose molecules, and
release them into the bloodstream, in a process
known as glycogenolysis.
As these stores become depleted, glucagon then
encourages the liver and kidney to synthesize
additional glucose by gluconeogenesis.
Glucagon turns off glycolysis in the liver, causing
glycolytic intermediates to be shuttled to
gluconeogenesis.
Glucagon also regulates the rate of glucose
production through lipolysis.
Somatostatin
Somatostatin (also known as growth
hormone-inhibiting hormone (GHIH)) is
a peptide hormone that regulates
the endocrine system and
affects neurotransmission and cell
proliferation via interaction with G proteincoupled somatostatin receptors and
inhibition of the release of numerous
secondary hormones.
Somatostatin has two active forms produced by
alternative cleavage of a single preproprotein: one of
14 amino acids, the other of 28 amino acids.
In the anterior pituitary gland, the effects of
somatostatin are:
Inhibit the release of growth hormone (GH) (thus
opposing the effects of Growth Hormone-Releasing
Hormone (GHRH))
Inhibit the release of thyroid-stimulating
hormone (TSH).
Pineal body
(epiphysis)
Melatonin, chemically N-acetyl-5-methoxy
tryptamine.
In animals, melatonin is involved in the
entrainment (synchronization) of the
circadian
rhythms
of
physiological
functions including sleep timing, blood
pressure
regulation,
seasonal
reproduction,
and
many
others.
In addition, melatonin has antioxidant
activity
Stomach
Gastrin is a peptide hormone that
stimulates secretion of gastric acid (HCl) by
the parietal cells of the stomach and aids in
gastric motility.
It is released by G cells in the pyloric
antrum of the stomach, duodenum, and
the pancreas.
Causes chief cells to secrete pepsinogen,
the zymogen (inactive) form of the
digestive enzyme pepsin.
Gastrin release is inhibited by:
1. The presence of acid (primarily the
secreted HCl) in the stomach (a case of
negative feedback).
2. Somatostatin also inhibits the release of
gastrin, along with secretin, GIP
(gastroinhibitory peptide), VIP (vasoactive
intestinal peptide), glucagon and
calcitonin.
Ghrelin, the "hunger hormone", also
known as lenomorelin (INN), is a peptide
hormone produced by ghrelinergic cells in
the gastrointestinal tract which functions
as a neuropeptide in the central nervous
system.
Ghrelin regulating appetite.
Ghrelin stimulates the release of growth
hormone, increase in hunger, modulation
of glucose and lipid metabolism, regulation
of gastrointestinal motility and secretion,
protection of neuronal and cardiovascular
cells, and regulation of immune function.
Neuropeptide Y (NPY) is a 36-amino acid
neuropeptide
that
acts
as
a
neurotransmitter in the brain and in the
autonomic nervous system of humans;
slight variations of the peptide are found in
many
other
animals.
In the autonomic system it is produced
mainly by neurons of the sympathetic
nervous system and serves as a strong
vasoconstrictor and also causes growth of
fat tissue.
Increased food intake and decreased
physical activity.
It can be associated with obesity.
Somatostatin is secreted at several
locations in the digestive system:
Delta cells in the pyloric antrum, the
duodenum and the pancreatic islets
Somatostatin released in the pyloric
antrum travels via the portal venous
system to the heart, then enters the
systemic circulation to reach the locations
where it will exert its inhibitory effects.
In addition, somatostatin release from
delta cells can act in a paracrine manner.
Suppress release of gastrin, cholecystokinin
(CCK), secretin, motilin, vasoactive
intestinal peptide (VIP), gastric inhibitory
polypeptide (GIP), enteroglucagon.
Lowers the rate of gastric emptying
Reduces smooth muscle contractions and
blood flow within the intestine.
Histamine
Enterochromaffin-like cells, located within
the gastric glands of the stomach, release
histamine that stimulates nearby parietal
cells by binding to the apical H2 receptor.
It stimulates gastric acid secretion
Endothelins
are
21-amino
acid
vasoconstricting
peptides
produced
primarily in the endothelium having a key
role
in
vascular
homeostasis.
Produced by X cells in the stomach and
stimulates smooth muscle contraction of
the stomach
Duodenum
(small intestine)
Secretin is a peptide hormone produced in
the S cells of the duodenum.
Secretin helps regulate the pH of the
duodenum by:
(1) inhibiting the secretion of gastric acid
from the parietal cells of the stomach and
(2) stimulating the production of
bicarbonate from the centroacinar cells
and intercalated ducts of the pancreas.
Secretin also stimulates bile production by
the liver; the bile emulsifies dietary fats in
the duodenum so that pancreatic lipase
can act upon them. Meanwhile, in concert
with secretin's actions, the other main
hormone simultaneously issued by the
duodenum, cholecystokinin, is stimulating
the gallbladder to contract, delivering its
stored bile for the same reason.
The mature secretin peptide is a linear
peptide hormone, which is composed of 27
amino acids and has a molecular weight of
3055.
Cholecystokinin (CCK or CCK-PZ; from
Greek chole, "bile"; cysto, "sac"; kinin,
"move"; hence, move the bile-sac
(gallbladder)) is a peptide hormone of the
gastrointestinal system responsible for
stimulating the digestion of fat and
protein.
Cholecystokinin,
previously
called
pancreozymin, is synthesized and secreted
by enteroendocrine cells (I cells) in the
duodenum, the first segment of the small
intestine.
Its presence causes the release of digestive
enzymes and bile from the pancreas and
gallbladder, respectively, and also acts as a
hunger suppressant.