Transcript Hormonal Regulation of Growth

Hormonal Regulation of
Growth
Hormonal Actions
 Definition
 Chemical messengers secreted by
various tissues, not necessarily secreted
by ductless glands.
 Hormones act in an endocrine manner
when secreted by cells and then
transmitted via the bloodstream to act
on distant target cells
Types of action
 Neurocrine
 Hormone is synthesized in a cell body of
a neuron and stored in axons such as
neurotransmmitters, but secreted into
the bloodstream to act on distant target
cells
 A key regulator of animal growth and
development by the hypothalamicpituitary-peripheral gland axes
Types of action (cont.)
 Local conveyance – site action
 Paracrine- when a hormone from one cell
is conveyed to an adjacent cell of
different type over a short distance via
interstitual fluid
 Autocrine – where a hormone from one
cell acts on itself or a neighboring cell of
the same type
 Intracrine – acts intracellularly and does
not require secretion to alter the process
Types of action (cont.)
 Tissue specificity
 Allows hormones to act on target tissues
without affecting other tissues or organs
 Receptors – has an affinity for specific
hormones that may be located at the cell
 Hormones will bind and act through
various enzyme systems, ion transport
or gene regulation
 Negative feedback loops may also
regulate hormonal function
Chemical Nature of Hormones
 Classification
 Peptides/amino acid derivatives
 Water soluble
 Ex. Thyroxine, LH, FSH
 Steroid/cholesterol derivatives
 Ex. Estrogen, testosterone, progesterone
 Fat soluble
Hypothalamic-Pituitary-Peripheral
Gland Axis
 Hypothalamus – the central organ of
the neuroendrocrine system
 Secretions from the Hypoth. Regulate
the secretions from the pituitary
 Located at the base of the brain
 Two sections: adenohypophysis and
neurohypophysis
Pituitary
 Adenohypophysis
 Pars tuberalis, pars intermedia, and pars
distalis (anterior = distalis)
 Neurohypophysis –
 Pars nervosa and pars eminens
(posterior= nervosa and intermedia)
 Consists of axons whose cell bodies are
in the hypothalamus
Posterior lobe
 Antidiuretic hormone (ADH) and oxytocin
are both synthesized in the hypothalamus
but are stored in the posterior pituitary
 ADH regulates water balance and oxytocin
regulates smooth muscle contractions in
mammary and uterine tissues
 Intermediate lobe is responsible for MSH
(melanocyte-stimulating hormone)
Anterior lobe
 Certain hormones are secreted as tropic
hormones that act on endocrine glands and
are synthesized in the hypothalamus
neuron cell bodies and stored in nerve
terminals (synaptosomes)
 Synaptosomes release hormones into the
hypothalamic-hypophyseal portal system
for transport to the anterior pituitary
 GHRH (growth hormone releasing
hormone) stimulates synthesis of GH
(somatotropin) whereby somatostatin
inhibits synthesis of somatotropin
Anterior Pituitary cont.
 GnRH (gonadotropin-releasing hormone)
induces gonadotrophs to produce FSH and
LH – these act on gonads
 Corticotropin-releasing hormone (CRH)
produces adrenocorticotropic hormone
(ACTH) – acts on adrenal gland
 Thyroponin-releasing hormone (TRH)
produces TSH (Thyroid Stimulating
Hormone) – act on thyroid glandProlactin is
synthesized by lactotrophs - Acts on
mammary and gonads
Anterior Pituitary cont.
 The tropin hormones are synthesized
by the anterior pituitary hormones to
target organs
 Typical target organs are: thyroid,
pancreas, adrenal glands, gonads,
etc.
Androgens
 Two types: testicular and adrenal
 Testicular hormones are testosterone
and androstenone
 Testosterone is produced in the
Leydig cells of the testes.
 Androstenone is a pheromone
 Known to contribute to the boar taint
odor in pork
Androgens
 Androstenone is stored in the salivary
gland and accumulates in fat depots
 Adrenal androgens are 17 keto steroids and
are synthesized by in the cortex of the
adrenal gland
 Growth effects are seen by the influence of
testosterone of bone and muscle. This is
seen by the increasing deposition of bone
salts. Thus, increased bone mass is seen
more in males
Androgens
 Muscle development is seen through
androgen secretions in three ways
 In utero, declines after birth, and increases at
puberty
 Prenatal androgens affects myogenesis
 Castrated males have lower circulating GH than
intact males
 Androgens increase both protein synthesis and
degradation, yet synthesis is stimulated greater
so we see an increase in protein accretion
Androgens
 Androgens synthesis induces the
development of mature male characteristics
such as: larger muscles in the forequarter,
neck and crest region.
 Castration diverts energy from growth of
muscle development to fat deposition
 Castration helps improve quality by less
muscle and more fat development at an
earlier age
Estrogens
 General classification for three hormones:
Estrone, Estriol, Beta-estradiol
 Responsible for: growth, maturation of
repro tract, female behavior, mammary
development
 Impact: bone, fat, and muscle tissue
growth
 Females have shorter skeletons due to:
earlier epiphyseal closure that is a result of
chondrocyte proliferation and a function of
bone formation
Estrogens
 Facilitates fat deposition
 Anabolic for ruminants
 Effective in castrate males for growth,
yet is less effective in non-ruminants
 Have little effect on intact males
 In steers, estrogens increases muscle
protein
 Table 10.1
Progestins
 Classified as steroid hormones
 Progesterone is a member of the
progestin family which is responsible
for maintenance of preg. And
mammary growth and devlepment
 MGA is a synthetic progestin that is
100X more potent than progesterone
 Improves F:G ratios in heifers and
suppresses estrus
Synthetic Hormones
 Anabolic steroids – those that result
in increased tissue accretion
 Androgens – improve growth, FE,
carcass protein esp. in heifers
 Testosterone is anabolic
 Combined with estrogens,
testosterone is more effective for
growth parameters
Synthetic Hormones
 TBA – Trenbolone Acetate – a synthetic
steroid is weak, yet when combined with
estrogen it is real effective in steers
 It binds to testosterone and estrogen
receptors in skeletal muscle.
 This yields a slight decrease in protein
synthesis and a significant result in
(decrease) in protein degradation, thus an
increase in protein accretion
Growth Hormone
GH or Somatotrophin (ST)
Produced by the anterior pituitary
Acts in an endocrine manner
Liver can synthesize growth factors
to help regulate growth, acts as a
mediator
 GH stimulates the production of IGF-I




Insulin-like growth factor-1; also called
somatomedin
Growth Hormone
 High concentrations of IGF-I inhibits GHRH
and GH, thus reduces production of IGF-I
 If IGF-I is too low then GHRH & GH are not
inhibited so they produce IGF-I
 Somatostatin is produced by the
hypothalamus and delta cells of the
pancreas that decreases GH secretion thus
decreases IGF-I production
 Table 10.5 Summary of GH Effects
Growth Hormone
 GH affects bone by using IGF-I to
increase chondrocyte proliferation
and osteoblast activity.
 GH increases lean growth by
increasing rates of muscle protein
synthesis and decreasing protein
degradation
 Increases in RNA & DNA accompany
increased protein accretion
Growth Hormone
 IGF-I actions on muscle include
increased uptake of glucose and
amino acids
 IGFBP (IGF binding proteins) help
transport IGF-I to target tissue like
muscle
 GH also increases lipolysis of fatty
acids from adipocytes
Growth Hormone
 GH is a protein hormone
 Therefore, it is not a orally active hormone
and admin. Via injection
 GH has been shown to increase wt. gain,
feed conversion while decreasing feed
intake
 When nutrients are limited, GH increases
lipolysis, and decreases growth because
IGF-I becomes uncoupled from GH,
therefore IGF-I decreases. These changes
causes a transfer of calories from adipose
to vital functions
IGF’s
 Are peptides that are structurally
similar to proinsulin and exhibit some
affinity for insulin receptors
 Insulin, at high conc., will bind to IGF
receptors.
 IGF’s are secreted by the liver and by
some other tissues in response to GH
but they are not stored in the liver
Insulin and Glucagon
 Islets of Langerhans within the
pancreas contains four types of cells




Alpha cells that synthesize glucagon
Beta cells that synthesize insulin
Delta cells that synthesize somatostatin
???? That synthesizes a pancreactic
polypeptide
Insulin
 At high conc. can stimulate general body
growth through low-affinity binding to IGF
receptors
 Even though there may a deficiency of
insulin receptors, the number of IGF
receptors are normal
 High circulating levels of insulin cause
overgrowth of extremities and enlargement
of the kidney and adrenal glands by cross
reacting with IGF receptors
Action of Insulin
 The actions of insulin on the global human
metabolism level include:
 Control of cellular intake of certain
substances, most prominently glucose in
muscle and adipose tissue (about ⅔ of body
cells).
 Increase of DNA replication and protein
synthesis via control of amino acid uptake.
 Modification of the activity of numerous
enzymes (allosteric effect).
The actions of insulin on cells
 glycogen synthesis – insulin forces storage of glucose
in liver (and muscle) cells in the form of glycogen;
lowered levels of insulin cause liver cells to convert
glycogen to glucose and excrete it into the blood. This
is the clinical action of insulin which is directly useful
in reducing high blood glucose levels as in diabetes.
 Increased fatty acid synthesis – insulin forces fat cells
to take in blood lipids which are converted to
triglycerides; lack of insulin causes the reverse.
 Increased esterification of fatty acids – forces adipose
tissue to make fats (ie, triglycerides) from fatty acid
esters; lack of insulin causes the reverse.
The actions of insulin on cells
 Decreased proteinolysis – forces reduction
of protein degradation; lack of insulin
increases protein degradation.
 Decreased lipolysis – forces reduction in
conversion of fat cell lipid stores into blood
fatty acids; lack of insulin causes the
reverse.
 Decreased gluconeogenesis – decreases
production of glucose from various
substrates in liver; lack of insulin causes
glucose production from assorted
substrates in the liver and elsewhere.
The actions of insulin on cells
 Increased amino acid uptake – forces cells
to absorb circulating amino acids; lack of
insulin inhibits absorption.
 Increased potassium uptake – forces cells
to absorb serum potassium; lack of insulin
inhibits absorption.
 Arterial muscle tone – forces arterial wall
muscle to relax, increasing blood flow,
especially in micro arteries; lack of insulin
reduces flow by allowing these muscles to
contract.
Insulin cont.
 There are two types of mutually
antagonistic metabolic hormones
affecting blood glucose levels:
 catabolic hormones (such as
glucagon, growth hormone, and
catecholamines), which increase
blood glucose
 and one anabolic hormone (insulin),
which decreases blood glucose
Insulin cont.
 Mechanisms which restore satisfactory
blood glucose levels after hypoglycemia
must be quick, and effective, because of
the immediate serious consequences of
insufficient glucose (in the extreme, coma,
less immediately dangerously, confusion or
unsteadiness, amongst many other
effects). This is because, at least in the
short term, it is far more dangerous to
have too little glucose in the blood than too
much.
Somatostatin
 Somatostatin is classified as an
inhibitory hormone, whose main
actions are to:
 Inhibit the release of growth hormone
(GH)
 Inhibit the release of thyroidstimulating hormone (TSH)
Somatostatin
 Suppress the release of
gastrointestinal hormones







Gastrin
Cholecystokinin (CCK)
Secretin
Motilin
Vasoactive intestinal peptide (VIP)
Gastric inhibitory polypeptide (GIP)
Enteroglucagon (GIP)
Somatostatin
 Lowers the rate of gastric emptying, and
reduces smooth muscle contractions and
blood flow within the intestine.
 Suppress the release of pancreatic
hormones
 Inhibit the release of insulin
 Inhibit the release of glucagon
 Suppress the exocrine secretory action of
pancreas.
 Somatostatin opposes the effects of Growth
Hormone-Releasing Hormone (GHRH)
Insulin and Glucagon
 Glucagon and Insulin act on a
negative feedback system
 When one goes up the other goes down
 Functions to mobilize glucose, fatty
acids, and increase amino acid
catabolism
 Insulin dominates the system in
mammals
Leptin
 Has been found to regulate body energy
storage
 It is a peptide produced by adipose tissue
 Appears to be important in providing
signals to the hypothalamus
 Ex. An increase in adipose tissue mass will
induce production of leptin and in return
will target the hypoth. to decrease food
intake, increase energy expenditure and
modulate other hormones such as insulin,
GH, cortisol, etc., thus ultimately reducing
adipose tissue mass
Glucocorticoids
 Glucocorticoids are a class of steroid
hormones characterised by an ability to
bind with the cortisol receptor and trigger
similar effects. Glucocorticoids are
distinguished from mineralocorticoids and
sex steroids by the specific receptors,
target cells, and effects. Technically, the
term corticosteroid refers to both
glucocorticoids and mineralocorticoids, but
is often used as a synonym for
glucocorticoid.
Cortisol
 Cortisol is a corticosteroid hormone
produced by the adrenal cortex that
is involved in the response to stress;
it increases blood pressure, blood
sugar levels, may cause infertility in
women, and suppresses the immune
system. Synthetic cortisol, also
known as hydrocortisone, is used as
a drug mainly to fight allergies and
inflammation.
Glucocorticoids
 Cortisol (or hydrocortisone) is the
most important human glucocorticoid.
It is essential for life and regulates or
supports a variety of important
cardiovascular, metabolic,
immunologic, and homeostatic
functions. Glucocorticoid receptors
are found in the cells of almost all
vertebrate tissues.
Glucocorticoids
 Stimulation of gluconeogenesis, particularly
in the liver: This pathway results in the
synthesis of glucose from non-hexose
substrates such as amino acids and lipids
and is particularly important in carnivores
and certain herbivores. Enhancing the
expression of enzymes involved in
gluconeogenesis is probably the best known
metabolic function of glucocorticoids.
Glucocorticoids
 Mobilization of amino acids from
extrahepatic tissues: These serve as
substrates for gluconeogenesis.
 Inhibition of glucose uptake in muscle and
adipose tissue: A mechanism to conserve
glucose.
 Stimulation of fat breakdown in adipose
tissue: The fatty acids released by lipolysis
are used for production of energy in tissues
like muscle, and the released glycerol
provide another substrate for
gluconeogenesis.
Glucocorticoids
 Glucocorticoids bind to the cytosolic
glucocorticoid receptor. This type of
receptor gets activated upon ligand binding.
After a hormone binds to the corresponding
receptor, the newly formed receptor-ligand
complex translocates itself into the cell
nucleus, where it binds to many
glucocorticoid response elements (GRE) in
the promoter region of the target genes.
The opposite mechanism is called
transrepression.
Glucocorticoids
 The activated hormone receptor
interacts with specific transcription
factors and prevents the transcription
of targeted genes. Glucocorticoids are
able to prevent the transcription of
any of immune genes, including the
IL-2 gene.
Glucocorticoids




Generally exhibit catabolic effects
Decreases muscle protein synthesis
Increases muscle protein degradation
Makes amino acids more available for
glucose production and increases
lipolysis by enhancing GH and
catecholamine-stimulated lipolysis
Catecholamines
 Catecholamines, adrenalin,
norepinephrine are all stored in the
adrenal medulla and is released when
stimulated by nerve fibers
 Acts on responses to stress
 Adrenalin (epinephrine) acts thru the
beta adrenergic receptors whereas
norepinephrine act on the alpha &
beta adrenergic receptors
Catecholamines
 Effects of epinephrine include mobilization
of glycogen for energy, increased blood
flow, respiration, and body temp.
 Epinephrine induces muscle anabolic
glycolysis to meet energy needs for muscle
contraction
 Stress induced situations lead to DFD and
PSE due to metabolic changes that create a
final pH alteration
 Long term stress leads to DFD while short
term or acute stress leads to PSE
Catecholamines
 Phenethanolamines are catecholamine like
synthethic cmpds that enhance growth and
compositional factors in animals
 Feeding of beta-adregenic agonists like
Ractopamine will increase lipolysis and
decrease lipogenesis, thus increasing
muscle by decreasing fat deposition and
enhancing protein synthesis to increase
muscle mass
 These changes may be a result of calpain
proteolytic activity
Catecholamines
 Calpains are a family of calciumdependent, non-lysosomal cysteine
proteases (proteolytic enzymes)
expressed ubiquitously in mammals
and many lower organisms.
 Calpain is also involved in skeletal
muscle protein breakdown due to
exercise and altered nutritional states
(Belcastro et al, 1996).
Catecholamines
 Zilpaterol is another beta agonists
approved in other countries but not
the U.S.
 Table 10.10
Thyroid Hormones
 T 3 (Thyroxine) and T 4 (triiodothyronine)
are produced in the thyroid glands
 They initiate insulin production in CHO
metabolism
 They work with GH to initiate protein and
nitrogen synthesis
 They stimulate both lipolysis & lipogenesis,
yet lipolysis is greater, thus adipose tissue
breakdown is greater
Parathyroid hormones
 PTH (Parathyroid hormone) is
produced by Chief cells in the
parathyroid gland
 PTH increase bone resorption to
increase calcium
 Calcium concentration in the muscle
are important in the contraction
process
Parathyroid hormones
 It enhances the release of calcium
from the large reservoir contained in
the bones, enhances reabsorption of
calcium from renal tubules; and
enhances the absorption of calcium in
the intestine by increasing the
production of vitamin D
Parathyroid hormones
 PTH also acts to decrease the concentration
of phosphate in the blood, primarily by
reducing reabsorption in the proximal
tubules of the kidney. The decreased
phosphate enhances bone demineralization.
 Increased calcium concentration in the
blood acts (via feedback inhibition) to
decrease PTH secretion by the parathyroid
glands. This is achieved by the activation of
calcium-sensing receptors located on
parathyroid cells.
Parathyroid hormones
 Bone resorption is the normal
destruction of bone by osteoclasts,
which are indirectly stimulated by
PTH. Stimulation is indirect since
osteoclasts do not have a receptor for
PTH; rather, PTH binds to osteoblasts,
the cells responsible for creating
bone.
Adrenal Glands
 In mammals, the adrenal glands
(also known as suprarenal glands)
are the triangle-shaped endocrine
glands that sit atop the kidneys.
 They are chiefly responsible for
regulating the stress response
through the synthesis of
corticosteroids and catecholamines,
including cortisol and adrenaline.
Adrenal Glands
 It is separated into two distinct
structures, the adrenal medulla and
the adrenal cortex, both of which
receive regulatory input from the
nervous system. As its name
suggests, the adrenal medulla is at
the center of the adrenal gland
surrounded by the adrenal cortex.
Adrenal Medulla
 The adrenal medulla is the body's main
source of the catecholamine hormones
adrenaline (epinephrine) and noradrenaline
(norepinephrine).
 Composed mainly of hormone-producing
chromaffin cells, the adrenal medulla is
the principal site of the conversion of the
amino acid tyrosine into the catecholamines
adrenaline (epinephrine) and noradrenaline
(norepinephrine).
Adrenal Cortex
 Some cells of the adrenal cortex
belong to the hypothalamic-pituitaryadrenal axis and are the source of
cortisol synthesis. Other cortical cells
produce androgens such as
testosterone, while some regulate
water and electrolyte concentrations
by secreting aldosterone.
Adrenal Cortex
 Situated along the perimeter of the adrenal
gland, the adrenal cortex mediates the
stress response through the production of
mineralocorticoids and glucocorticoids,
including aldosterone and cortisol
respectively. It is also a secondary site of
androgen synthesis.
 All adrenocortical hormones are
synthesised from cholesterol.