hormones - umlub.pleffects by ‘second messengers’, which are activated in the cell as soon as...
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Hormones
Napoleon Cybulski – discovererof adrenaline”, 1895)
Ernest Starling – introducedthe term ’hormone’ (1905), discovered secretin
Hormon (gr. hormao)
Types of intercellular communication
• Autocrine
• Paracrine
• Endocrine
• Synapses
• Slot connections (nexus)
Systems of Internal Communication
– the nervous system
– the endocrine system
Systems of Internal Communication
• The nervous system conveys high-speed electrical
signals along specialized cells called neurons.
• The endocrine system, made up of endocrine glands,
secretes hormones that coordinate slower but longer-
acting responses to stimuli.
Hormones
• A hormone is a chemical signal that is secreted into the
circulatory system and communicates regulatory
messages within the body.
• Hormones may reach all parts of the body, but only
certain types of cells, target cells, are equipped to
respond.
Hormones
Advantages of using chemical messengers:
– Chemical molecules can spread to all tissues through the blood.
– Chemical signals can persist longer than electrical ones.
– Many different kinds of chemicals can act as hormones; different
hormones can target different tissues.
Hormone Action
• Secretion into the bloodstream by specialized cells
arranged in glands
• A specific biological effect occurs when hormone
combines with a receptor on the target cell
• Within 1 min after the secretion, hormon is throughout
the whole body
Glands
• Many hormones are secreted by ductless endocrine glands.
– Obtain raw materials from and secrete hormones directly into the bloodstream
• Exocrine glands have ducts for discharging secretions onto a free surface.– Sweat glands, salivary glands, enzyme-secreting glands in the
digestive tract
Hormone action
• All hormones act on cells by way of their ‘receptors’.
• Each hormone has its own receptor to which it binds,
matching rather like a lock and key. This is why
hormones circulating throughout the body in the blood
may leave capillaries to enter the extracellular fluid of
many tissues, but act only on those cells which possess
the appropriate receptor.
The role of receptors in hormone action
Hormone classification
• Peptide hormones
• Amino acid-derived hormones (thyroid hormones,
biogenic amines)
• Cholesterol-derived hormones (adrenal hormones)
• Fat-soluble hormones
• Water-soluble hormones
• Proteins and peptides cannot enter the cell and therefore
they act via cell membrane receptors, producing their
effects by ‘second messengers’, which are activated in
the cell as soon as the hormone binds to the receptor.
Thus peptide hormones can produce quite rapid
responses.
• Steroid and thyroid hormones, by contrast, can enter the
cell and bind to intracellular receptors, producing their
effects by stimulating the production of new proteins.
There is therefore a relatively long lag period before the
response to these hormones is seen.
Function of Receptor
• pick up signals which cell is interested in
• intensify the weak signals
• translate the language of hormones into language
understandable to cell
The impact of the lipophilic properties on
hormones actionWater-soluble
hormone
Fat-soluble
hormone
secondary
messenger
Effects of hormones action
• metabolic changes in a cell (eg. increase of glucose
uptake in response to insulin)
• stimulation of cell division (eg. growth hormone)
• changes gene expression (stimulation or inhibition
production of specific protein products)
Mechanism of hormone action
PROTEIN
PRODUCT
A hormone-receptor
complex can be
transcription factor of
particular genes
Membrane-Bound Receptors• Many hormones are too
large, or too polar, to pass through plasma membranes.
– Bind to transmembrane proteins that act as receptor sites on target cell membranes.
• Hormone is first messenger.
• Causes activation of a second messenger in the cytoplasm.
– Ca2+
– cAMP
– triphosphate (IP3) and diacylglycerol (DAG)
Nuclear Receptors
• Steroid hormones are lipid soluble molecules that bind to hormone receptors in the cytoplasm of the target cell.
– Site of activity is the nucleus.
• Steroids are manufactured from cholesterol.
• Estrogen, progesterone, testosterone, cortisol.
Nuclear Receptors
• Thyroid hormones
also act through
nuclear receptors.
– Binds to
transmembrane
protein that uses
ATP to move it into
the cell.
Control Pathways and Feedback Loops
• A common feature of control pathways is a feedback loop connecting the response to the initial stimulus.
• Negative feedbackregulates many hormonal pathways involved in homeostasis.
The hypothalamic–pituitary–
adrenal axis (HPA axis or
HTPA axis), also known as
the limbic–hypothalamic–
pituitary–adrenal axis (LHPA
axis), is a complex set of direct
influences and feedback
interactions among three
endocrine glands: the
hypothalamus, the pituitary
gland (a pea-shaped structure
located below the
hypothalamus), and the
adrenal (also called
"suprarenal") glands (small,
conical organs on top of the
kidneys).
• The hypothalamus regulates the
neuroendocrine system, maintaining
homeostasis in the body.
– The hypothalamus can use motor
nerves to send short-lived electrical
messages or hormones to send
chemical messages with a longer
duration.
The hypothalamus
Oxytocin and vasopressin – produced by the hypothalamus
and stored and secreted into the bloodstream from the
posterior pituitary gland
Releasing hormones (factors) or liberins
Inhibiting hormones (factors) or statins
The Chain of Command
• The hypothalamus produces different
“releasing”/”inhibiting” hormones that
travel to the pituitary gland.
• Each releasing/ inhibiting hormone
stimulates or inhibites the pituitary to
release a corresponding hormone which
travels to an endocrine gland and causes
it to start producing a particular endocrine
hormone.
Liberins/statins
Hypothalamic releasing
hormone
Effect on pituitary
Corticotropin releasing hormone
(CRH)
Stimulates ACTH secretion
Thyrotropin releasing hormone
(TRH)
Stimulates TSH and Prolactin
secretion
Growth hormone releasing
hormone (GHRH)
Stimulates GH secretion
Somatostatin Inhibits GH (and other
hormone) secretion
Gonadotropin releasing
hormone (GnRH) a.k.a LHRH
Stimulates LH and FSH
secretion
Prolactin releasing hormone
(PRH)
Stimulates PRL secretion
Prolactin inhibiting hormone
(dopamine)
Inhibits PRL secretion
Hypothalamus
Anterior pituitary Posterior pituitary
Thyrotropin
ACTH
Somatotropin
LH
FSH
Prolactin
Vasopressin
Oxytocin
Thyroid
Adrenal
CortexAdrenal
MedullaPancreas Ovary Testis
Muscles
liver Tissues
Liver,
muscles
Estradiol TestosteroneInsulin,
glucagon,
somatostatin
T3, T4Cortisol
aldosterone
Mammary
glands
Reproductive
organs
Epinephrine
Releasing
hormones
Nervous
The Pituitary
• The pituitary gland
is located below the
hypothalamus.
• Nine major hormones
are produced here.
• These hormones act
primarily to influence
other endocrine
glands.
Pituitary
Pro-opiomelanocortin (POMC) hormones
Follicle stimulating hormone (FSH)
Luteinizing hormone (LH)
Somatotropin (GH)
Prolactin (PRL)
Thyrotropin (TRH)
Liberins/Statins
Vasopressin (ADH)
Oxytocin
Peptide hormones
The Pituitary
• The posterior lobe of the pituitary regulates water
conservation, milk letdown, and uterine contraction in
women.
• The anterior lobe regulates the other endocrine glands.
The Anterior Pituitary
• Thyroid stimulating hormone (TSH) – stimulates the thyroid gland to produce thyroxine which stimulates oxidative respiration.
• Luteinizing hormone (LH) plays an important role in the menstrual cycle. It also stimulates the production of testosterone in males.
The Anterior Pituitary
• Follicle-stimulating hormone (FSH) – plays an important role in the menstrual cycle. In males, it causes the testes to produce a hormone that regulates sperm production.
• Adrenocorticotropic hormone (ACTH) –stimulates the adrenal gland to produce steroid hormones. Some regulate glucose production, others balance sodium & potassium in the blood.
The Anterior Pituitary
• Growth hormone (GH) – stimulates the growth of
muscle and bone.
• Prolactin – stimulates milk production.
The Posterior Pituitary
• Antidiuretic hormone (ADH) regulates the kidney’s retention of water.
• Oxytocin initiates uterine contraction during childbirth and milk release in mothers.
• These hormones are actually synthesized in the hypothalamus and stored in the posterior pituitary.
Biological Clocks
• The pineal gland is
located in the brain
of most vertebrates.
– Evolved from a light
sensitive “third eye”.
– Primitive fish &
some reptiles still
have a third eye.
Biological Clocks
• In other vertebrates it functions as an endocrine gland secreting melatonin.
• Melatonin controls color change in amphibians & reptiles.
• Release of melatonin is controlled by light/dark cycles.
• The primary functions of melatonin appear to be modulation of sleep patterns in both circadian and seasonal cycles– Circadian rhythms – 24 hours long.
The thyroid gland
- The thyroid gland produces three hormones in response to TSH release by
thyrotroph cells of the anterior pituitary:
1) Triiodothyronine (T3) - made in follicle
2) Thyroxine (T4) - made in follicle
T3 and T4 are dependent on iodine for synthesis
T4 is the more prevalent in humans (98% of circulating iodinated thyroid hormone)
T3 and T4 regulate body growth and metabolism, and are important in development and
maturation of the brain and nervous system
3) Calcitonin - made by C cells
- decreases blood calcium levels and blood phosphate levels (by helping them get
deposited in bone, and by stimulating excretion of them by kidneys)
The Thyroid
• The hypothalamus
and anterior pituitary
control the secretion
of thyroid hormones
through two negative
feedback loops.
• TRH- thyrotropin-releasing
hormone
• TSH - thyroid-stimulating hormone
• Triiodothyronine (T3)
• Thyroxine (T4)
thyrotropin-releasing hormonethyrotropin-releasing hormone
The Thyroid• The thyroid hormones
play crucial roles in
stimulating
metabolism and
influencing
development and
maturation.
Thyroid hormones
T4
T3
TSH
Thyroid hormones
T4
T3 ↓TSH
↑T3
↑T4
Graves-Basedow disease
Thyroid hormones
T4
T3 ↑TSH
↓T3
↓T4
TSH
Hashimoto disease
The Parathyroids
• The parathyroid glands are
four small glands attached
to the thyroid.
• The hormone they produce
is parathyroid hormone
(PTH) which regulates the
level of calcium in the blood.
– Essential that calcium is
kept within narrow limits
for muscle contraction,
including the heart.
Calcium Homeostasis
• Two antagonistic
hormones,
parathyroid
hormone (PTH) and
calcitonin, play the
major role in calcium
(Ca2+) homeostasis in
mammals.
Calcium Homeostasis
• Calcitonin, secreted by the thyroid gland,
stimulates Ca2+ deposition in the bones and
secretion by the kidneys, thus lowering blood
Ca2+ levels.
• PTH, secreted by the parathyroid glands, has
the opposite effects on the bones and kidneys,
and raises Ca2+ levels.
– Also has an indirect effect, stimulating the kidneys to
produce activate vitamin D, which promotes intestinal
uptake of Ca2+ from food.
The Adrenals
• Mammals have an adrenal gland above each kidney.
– Adrenal medulla is the inner core which produces
adrenaline (epinephrine) and norepinephrine.
– Adrenal cortex is the outer shell that produces the
steroid hormones cortisol and aldosterone.
The adrenal glandsAdrenal medulla (catecholamines):
• epinephrine & norepinephrine - increase basal
metabolic rate (blood glucose and pressure)
Adrenal cortex (corticoids):
• glucocorticoids (corticosterone, cortisol,
hydrocortisone) – inhibit incorporation of amino
acids into protein muscles, stimulate formation
and storage of glycogen, help maintain normal
blood sugar level
• mineralocorticoids (aldosterone,
deoxycorticosterone) – regulate metabolism of
Na+ and K+
• sex hormones (especially androstenedione) –
regulate facial and body hair
Adrenal Medulla
• The adrenal medulla releases adrenalin (epinephrine)
and norepinephrine in times of stress.
– Identical to the effects of the sympathetic nervous system, but
longer lasting.
• Accelerated heartbeat, increased blood pressure, higher levels of
blood sugar and increased blood flow to heart and lungs.
Adrenal Cortex
• The adrenal cortex produces the steroid hormone
cortisol (hydrocortisone).
– Reduces inflammation.
• Synthetic derivatives such as prednisone are used as anti-
inflammatory agents.
– Stimulates carbohydrate metabolism.
Adrenal Cortex
• The adrenal cortex also produces aldosterone.
• Aldosterone acts in the kidney to promote the uptake of sodium & other salts from the urine.– These salts are important in nerve conduction.
• Aldosterone and PTH are the only two hormones essential for survival.
The Pancreas
• The pancreas is located
behind the stomach and
is connected to the small
intestine by a small tube.
• It secretes digestive
enzymes into the
digestive tract (exocrine
function).
• Endocrine function –
production of insulin
and glucagon.
The endocrine cells of the pancreas
exist in islets of tissue that are
surrounded by exocrine cells.
1. Islets of Langerhans
• Alpha cells:
- glucagon - raises blood glucose levels
• Beta cells:
- insulin - lowers blood glucose levels
2. Other cells (delta cells) of the
pancreas produce somatostatin, SS,
SOM) – lowers secretion of insulin
and glucagon
The pancreas
insulin:
- stimulates uptake of glucose (and amino acids) by muscle
and liver cells
- inhibits production of glucose in liver (gluconeogenesis,
glycogenolysis)
- stimulates incorporation of fatty acids in fats
- stimulates protein synthesis in muscle and liver
glucagon:
- stimulates production of glucose in liver (gluconeogenesis,
glycogenolysis)
- stimulates lipolysis (breakdown of fats to free fatty acids +
glycerol)
Note: glucagon and insulin work in opposition,
and their combined effects control blood glucose
Prevents hypoglycemia
Prevents hyperglycemia
Diabetes
• Diabetes mellitus, perhaps the best-known endocrine
disorder, is caused by a deficiency of insulin or a
decreased response to insulin in target tissues.
– Marked by elevated blood glucose levels.
Diabetes
• Type I diabetes mellitus (insulin-dependent
diabetes) is an autoimmune disorder in which
the immune system destroys the beta cells of
the pancreas.
• Type II diabetes mellitus (non-insulin-dependent
diabetes) is characterized either by a deficiency
of insulin or, more commonly, by reduced
responsiveness of target cells due to some
change in insulin receptors.
The gonads
Steroid hormones: precursor is cholesterol
• Testes:
Androgens (testosterone, dihydrotestosterone) – stimulate development and
maintenance of male primary and secondary sexual characteristics and
behavior
• Ovaries:
Estrogens (estradiol, estrone, etc) - stimulate development and maintenance
of female secondary sexual characteristics and behavior
Progestins (progesterone) - stimulate female secondary sexual
characteristics and behavior, maintain pregnancy
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