Location of Hypothalamus & Pituitary Image: http://www.umm.edu/patiented/articles/hypothalamus_000337.htm
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Location of Hypothalamus & Pituitary
Image: http://www.umm.edu/patiented/articles/hypothalamus_000337.htm
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Hypothalamus
Mamillary Bodies
Control Feeding reflexes
(licking, chewing,
swallowing, etc).
Autonomic Centres
(Sympathetic/Parasympathe
tic)
Regulate heart rate & blood
pressure.
Tuberal Nuclei
Release peptide hormones
that targets the anterior
pituitary
(adenohypophysis).
Supraoptic
NucleusProduce & secretes
ADH via posterior
pituitary
Paraventricular
Nucleus
Produce & secretes
oxytocin via posterior
pituitary
Preoptic
area
Regulatebody
temperature.
Suprachiasma
tic nucleus
Coordinates
day-night
cycles of
activity.
Image: Frederic H. Martini, Anatomy & Physiology, 2 nd Edition, Pearson 2010, Figure 13-10,
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Hypothalamus-Pituitary Axis
Anterior Lobe Pathway
1. Swelling near infundibulum,
allowing hypothalamus to release
regulatory factors into interstitial
fluids2. Factors travels and enters capillary
network at median eminence
region
3. Travels to the capillary network in
anterior lobe region via portal vein& flow from the superior
hypophyseal artery.
4. Bind to receptors of endocrine cells
5. Hormones released into circulation.Image: Frederic H. Martini, Anatomy & Physiology, 2 nd Edition, Pearson 2010, Figure 16-7, page 523.
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Hypothalamus-Pituitary Axis
Posterior Lobe Pathway
1. Neurons of supraoptic &
paraventricular releases ADH &
Oxytoxin respectively.
2. Move along the axons in
infundibulum & gets released
at posterior pituitary capillary
network.
3. Hormones released into thecirculatory by the flow from
inferior hypophyseal artery.
Image: Frederic H. Martini, Anatomy & Physiology, 2 nd Edition, Pearson 2010, Figure 16-7, page 523.
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Pituitary Gland
Thyroid-
stimulatingHormone (TSH)
Targets thyroid
gland and
release thyroid
hormones
Adrenocor ticotro
pic Hormone
(ACTH)Targets cells that
produce
glucocorticoids,
hormone that
affect glucose
metabolism
Gonadotropins
Regulates activitiesof gonads,
releasing..
Follicle-
stimulating
Hormone (FSH)
Luteinizing
hormone
(LH)
Important for
sexual maturation
Prolactin
(PRL)
Works with
other
hormones to
stimulate
mammary
gland
developmentGrowthHormone
(GH)
Stimulates cellgrowth and
replication, by
Melanocyte-
Stimulating
Hormone(MSH)
control skin
pigmentation
Antidiuretic
hormone (ADH)
Regulates
osmotic
concentration of
body fluids
Oxytoxin
(OX
T)Helps in
pregnancy,
promoting
labor and
delivery.
(posterior lobe)
Image: Frederic H. Martini,
Anatomy & Physiology, 2 nd
Edition, Pearson 2010, Figure16-6, page 522.
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Hypothalamic-Pituitary HormonesAssociated with Growth & Maturation
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Growth Hormone (GH)
Indirect Action
Stimulate growth by accelerating rate of protein synthesis by:1. GH acts on liver to release somatomedins
(aka insulin-like growth factors,IGFs)2. Somatomedins bind to receptor on
plasma membrane of skeletal musclefibers, cartilage cells and other targetcells.
3. Stimulate target cells to increase uptakerate of amino acids and their
incorporation into new proteins.4. Important after consumption of a meal as
blood contains high concentration of glucose and amino acids.
1. Glucose metabolism to obtain ATP
2. Amino Acids Used for protein synthesis.
Hypothalamus-Pituitary AxisAssociated with Growth & Maturation
Image: Frederic H. Martini, Anatomy & Physiology, 2 nd Edition, Pearson 2010, Figure 16-8, page 524.
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Growth Hormone (GH)
Direct Action
More selective & only appear after
blood glucose and amino acid
concentration have returned back tonormal.
Mostly associated with metabolism.
Hypothalamus-Pituitary AxisAssociated with Growth & Maturation
Image: Frederic H. Martini, Anatomy & Physiology, 2 nd Edition, Pearson 2010, Figure 16-8, page 524.
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Growth Hormone (GH)
Regulation by Negative Feedback
Production of GH is activated by
growth hormone releasing hormone
(GHRH) & inhibited by growth
hormone-inhibiting hormone (GHIH)
Somatomedins stimulate GHIH &
inhibits GHRH.
Hypothalamus-Pituitary AxisAssociated with Growth & Maturation
Image: Frederic H. Martini, Anatomy & Physiology, 2 nd Edition, Pearson 2010, Figure 16-8, page 524.
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GonadotropinsRegulates activity of gonads and important for sexual maturation.
Two gonadotropins are:
1. Follicle-stimulating hormone (FSH)Male: stimulates nurse cells in testis to undergo physical maturation for sperm
development
Female: acts with luteinizing hormone to promote follicle development &
stimulates ovarian cells to secrete estrogens.
2. Luteinizing hormone (LH)
Male: Stimulates testis to produce androgen, such as testosterone.
Female: induces ovulation, leading to production of reproductive cells & stimulates
ovaries to secrete estrogens and progestins, such as progesterone.
Hypothalamus-Pituitary AxisAssociated with Growth & Maturation
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Regulation of Gonadotropins (FSH & LH)
Production of FSH & LH is activated by
Gonadotropin-releasing hormone (GnRH) as a
releasing hormone (RH)
FSH & LH - Hormone 1 - binds to receptors of
respective target organ
Binding leads to maturation of sexual
organs/tissues & release of various secondary
hormones Hormone 2 which sends a
negative feedback, inhibiting production of gonadotropins.
± FSH production is inhibited by inhibin
± LH production is inhibited by estrogens, progestins and
androgens.
Hypothalamus-Pituitary AxisAssociated with Growth & Maturation
Image: Frederic H. Martini, Anatomy & Physiology, 2 nd Edition, Pearson 2010, Figure 16-8, page 524.
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Thyroid Hormone
Development of the skeletal,muscular and nervous system ingrowing children.
T4 important for skin development
before puberty.
Regulation by Negative Feedback
± Production & release of TSH isactivated by TRH.
± TSH binds to membrane receptors andby stimulating adenylate cyclase,activates key enzymes involved inthyroid hormone production.
± Circulating thyroid hormones (T3 & T4)
inhibits production of TRH & TSH.
Hypothalamus-Pituitary AxisAssociated with Growth & Maturation
Image (edited): Frederic H. Martini, Anatomy & Physiology, 2 nd Edition, Pearson 2010, Figure 16-8, page 524.
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Mechanism of ThyroidHormone synthesis, storage and secretion:
1. Iodine ions (I-) absorbed from diet at the digestive tract travels via
bloodstream to the thyroid gland, transported into cytoplasm viacarrier proteins in the basal membrane of follicle cells.
2. Iodine ions diffuse to the apical surface of each follicle cells,
converted to activated form of iodide (I+) by enzyme thyroid
peroxidase.
3. Tyrosine molecules to which iodide ions have been attached
become linked covalently, forming molecules of thyroid hormones
(Thyroxine aka tetraiodothyronine T4 and triiodothyronine T3).Process is (probably) by thyroid peroxidase, remain incorporated
into thyroglobulin.
4. Follicle cells remove thyroglobulin from follicle cells by
endocytosis.
5. Lysosomal enzymes breaks down thyroglobulin allowing amino
acids and thyroid hormones to enter cytoplasm. (amino acids
recycled to synthesize more thyroglobulin)
6. T3 & T4 diffuse across basement membrane and enters
bloodstream.
7. Approx. 70% of T3 and 75% of T4 gets attached to transport
proteins called thyroid-binding globulins (TBGs). The rest are
attached to thyroid-binding prealbumin (TBPA) or to albumin.
Only small amount (0.3% of T3 and 0.03% of T4) are circulating
freely.
Hypothalamus-Pituitary AxisAssociated with Growth & Maturation
Image: Frederic H. Martini, Anatomy & Physiology, 2 nd Edition, Pearson 2010, Figure 16-11, page 530.
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Prolactin (PRL) Works with other hormones in
stimulating mammary glanddevelopment
Stimulates milk production bymammary glands
Regulation by negative feedback
± Production of PRL is stimulated byprolactin-releasing factors (PRF)
± Circulating PRL Inhibits PRF
stimulates prolactin-inhibiting hormone
(PIH), which inhibits PRL production
Hypothalamus-Pituitary AxisAssociated with Growth & Maturation
Image: Frederic H. Martini, Anatomy & Physiology, 2 nd Edition, Pearson 2010, Figure 16-8, page 524.
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Insulin ± Growing cells need adequate supply of energy and
nutrients. Without insulin, passage of glucose andanimo acids across plasma membrane will be
drastically reduced or eliminated
Parathyroid Hormone (PTH) & Calcitriol
± Promote absorption of calcium salts for
subsequent deposition in bone. Without adequatelevel of both hormones, bones can still enlarge,but will be poorly mineralized, weak and flexible.(e.g. rickets)
Other HormonesAssociated with Growth & Maturation
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Insulin Regulation
Respond to level of glucose
Elevated level
± Insulin released, glucose enters cells.
Declined level
±Glucagon released, liver releasedglucose in blood.
Image: http://www.endocrineweb.com/conditions/diabetes/normal-regulation-blood-glucose
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Parathyroid Hormone (PTH) &
Calcitriol Regulation
Respond to levels of calcium
Elevated calcium
± Release of calcitonin, blood
calcium level falls.
Declined calcium
± PTH released, blood level rises.
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Hypothalamus-Pituitary AxisAssociated with Growth & Maturation
Image: Boron and
Boulpaep, Medical
Physiology, 1st edition,Saunders 2003, Figure
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References
Boron and Boulpaep, Medical Physiology, 1st edition,Saunders 2003.
Frederic H. Martini, Anatomy & Physiology, 2nd Edition,Pearson 2010.
Igor Mitrovic (MD), Introduction to the Hypothalamo-Pituitary-Adrenal (HPA) Axis.
F. Rastinejad, Hypothalamic/Pituitary Axis: Adrenals andThyroid, Medical Pharmacology.
A.D.A.M., Inc.
Mc Graw Hill Companies Inc, Ganongs Review of MedicalPhysiology, 23rd Edition, 2010.
Rang & Dale, Pharmacology, 5th Edition, 2003.
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Gigantism
a rare childhood condition caused by
hyper-secretion of growth hormones (usually causedby pituitary adenoma) prior to epiphyseal closure.Increased amounts of GH results in overgrowth of bones and abnormally tall stature.
Treatments
Surgery- removal of tumors with well-defined
borders
Drugs
Somatostatin analogs- Inhibits the release of growth hormones and thyroid stimulating hormonesfrom the anterior pituitary.
Ex: Octreotide, Lanreotide
Dopama
Pegvisomant- Growth hormone blocker; blocks theeffects of growth hormones
Radiation is used to bring GH levels to normal;takes time and may cause low levels of otherpituitary hormones
Congenital Adrenal Hyperplasia
an inherited disorder that causes
enzyme deficiency resulting in the inability of adrenal glands to produce hormones necessary tolife. In the non-salt wasting form of this disorder, theadrenal glands are unable to produce cortisol andinstead, are shifted away to produce other hormonessuch as androgens. Excessive androgen results inprecocious puberty, rapid growth, bone aging, andambiguous genitalia for females.
Treatment
Hydrocortisone- Cortisol replacement
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If left untreated,
Gigantism
Abnormally large stature- Increased metabolic state resulting in faster degeneration of
cells which results in a decrease in life expectancy.
May also cause emotional stress and low self esteem.
CAH
Early maturation of bones- Once bones reach maximum maturity, growth stops and
results in a short adult stature.
Untreated CAH may result in precocious puberty wherein sexual and physical
characteristics mature earlier than normal.
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Q 1bPhysical examination
Tall, well proportioned and markedly muscular. Mild facial acne, fine pubic hair, adult-likedistribution pattern.
Large penis, but normal testes size.
Hormone levels: ± Testosterone: 172 ng/dl
± 17-OH-progesterone: 12,000 ng/dl (basal) and 22,000ng/dl (ACTH stimulation)
± Cortisol: 5 µg/dl (basal) and 10 µg/dl (ACTH
stimulation) Normal neurological signs.
What is Jims problem?
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Gigantism
Gigantism ± Increased skeletal growth
velocity
± Increased body size withdisproportionately long arms
and legs ± Delayed puberty
± Hypogonadotropichypogonadism
± Headache and visual changes
Not the cause of Jimsproblem
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Precocious puberty
Definition: onset of sex maturation before age 8
in girls or age 9 in boys.
2 types:
± GnRH-dependent
± GnRH-independent
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GnRH-dependent The hypothalamic-pituitary-gonad axis is
activated.
Cause: CNS disorders
Symptoms:
± Enlargement of gonads
± Enlargement of penis
± Pubic hair appearance
± Facial acne
± Neurological symptoms, including developmental
delay
Not the cause of Jims problem
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GnRH-independent
Congenital adrenal hyperplasia
21-hydorxylase deficiency
impaired biosynthesis of cortical steroids
steroidogenesis channeled to androgen
production
Sex-enhancing symptoms - virilisation.
The true cause of Jims problem
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Q n 2
Pathology of CAH (diagram)
Normal values of various hormones listed
compare with Jims values
explain diagnosis
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Q uestion 3
Initial Treatment for Jims Adrenal Hyperplasia
and its mechanism
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Q uestion 4
What happens upon 21-hydroxylase
deficiency?
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ACTH
Adrenal Gland
Stimulation
Cholesterol
Mineralocorticoids Glucocorticoids Sex Steroids
Aldosterone Cortisol Testesterone
Pregnenolone
17-Hydroxypregnenolone Dehydroxyepiandrosterone
17-Hydroxyprogesterone
11-Deoxycortisol
Androstenedione
Progesterone
11-Deoxycorticosterone
Corticosterone
17
17
21
21
11
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What other treatment is available for thecorrection of this deficiency?
Severe 21-hydroxylase deficiency salt-wasting
75% requires aldosterone replacementMineralocorticoid alpha fludohydrocortisonetherapy & NaCl
Aromatase inhibitors slow its maturation
Suppress precocious puberty long acting GnRHagonists while simultaneously stimulating growthwith GH
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Conclusion
The Hypothalamic-Pituitary-Adrenal axis plays a
vital role for growth and maturation especially
for normal puberty. As seen in Jims case who
suffers from Congenital Adrenal Hyperplasia, the
condition in which one of the enzymes
important for hormone synthesis in the adrenal
gland is deficient leading to precocious puberty.