Hypophysis (Pituitary Gland)

Taradi 1interactive physiology hypophysis
PITUITARY GLANDPITUITARY GLAND
(HYPOPHYSIS)(HYPOPHYSIS)
Prof. Milan Taradi, MD, PhD
Department of Physiology
and Immunology
Medical Faculty, Zagreb

Pituitary Hormones and Their TargetsPituitary Hormones and Their Targets
o At the size of a
pea, the
pituitary
gland rules as
the
bandmaster in
orchestra of all
glands.
o The
hypothalamus
is the true
“master
gland”.

Three Levels of Endocrine ControlThree Levels of Endocrine Control
IntegrationIntegration
o Hormones of
the
hypothalamic-
anterior
pituitary
pathway.
o Hypothalamus
pituitary
trophic
hormone
pathways
coordinate
endocrine
regulation.

Gross anatomyGross anatomy
o The pituitary gland
is a small gland
about
o 1 centimeter in
diameter and
o 0.5 to 1 gram in
weight.

MidsaggitalMidsaggital SSection of theection of the HHumanuman BBrainrain
o Midsaggital
section of the
human brain (from
the XIX century wax
collection of human brains at
the Museum of the
Department of Human
Anatomy of the Unversity of
Bologna, Italy).
o The
hypothalamus
(asterisk) lies
above the
pituitary gland
(cross).

Magnetic Resonance ImageMagnetic Resonance Image
o MRI (A) and corresponding schematic
illustration (B) of the human hypothalamus (H)
and pituitary gland seen in saggital orientation.

Magnetic Resonance ImageMagnetic Resonance Image
o MRI (A) and schematic image (B) of the pituitary fossa and
its anatomic relationships seen in coronal orientation.

Anatomy of theAnatomy of the PPituitaryituitary GGlandland
o The pituitary gland is a roundish organ that lies immediately
beneath the hypothalamus, resting in a depression of the base of
the skull called the sella turcica ("Turkish saddle").
o In an adult human the pituitary is roughly the size and shape of a
pea.

Gross AnatomyGross Anatomy
o The anterior pituitary
(adenohypophysis) is a
classical gland composed
predominantly of cells that
secrete protein hormones.
o The posterior pituitary
(neurohypophysis) is an
extension of the
hypothalamus and it is
composed largely of the
axons of hypothalamic
neurons which extend
downward as a large bundle
behind the anterior pituitary.
o It also forms the so-called
pituitary stalk, which appears
to suspend the anterior gland
from the hypothalamus.

Pituitary DevelopmentPituitary Development
o The boundary epitheilal
ectoderm in the roof of the
pharynx forms a pocket
(Rathke's pouch) that comes
into contact with the
ectoderm of developing
brain.

Pituitary DevelopmentPituitary Development
o The anterior pituitary
originates from the
epitheilal ectoderm.
o The posterior pituitary
originates from the
brain neuroectoderm.

Microscopic AnatomyMicroscopic Anatomy
o The pituitary gland or
hypophysis is derived
from two
embryologically-
distinct tissues:
o the anterior lobe
o the intermediate lobe
o the posterior lobe

Histology of theHistology of the
AdenohypophysisAdenohypophysis
o Three distinct cell
types are seen among
epithelial cells:
o Acidophils have
cytoplasm that stains
red or orange.
o Basophils have
cytoplasm that stains a
bluish color.
o Chromophobes have
cytoplasm that stains
very poorly.

The Adenohypophyse ContainsThe Adenohypophyse Contains
Several Different Cell TypeSeveral Different Cell Type
o Acidophils
o Somatotropes which produce growth hormone
o Lactotropes which produce prolactin
o Basophils
o Thyrotropes which produce thyroid stimulating
hormone
o Gonadotropes which produce luteinizing hormone or
follicle-stimulating hormone
o Corticotropes which produce adrenocorticotrophic
hormone
o Chromophobes
o These are cells that have minimal or no hormonal
content.

Histology of theHistology of the
NeurohypophysisNeurohypophysis
o The large numbers of axons are observed,
sprinkled with glial cells and capillaries.

Posterior Pituitary Hormons are SynthesizedPosterior Pituitary Hormons are Synthesized
by Cell Bodies in the Hypothalamusby Cell Bodies in the Hypothalamus
o The bulk of the neurohypophysis is composed on largely
unmyelinated axons from hypothalamic neurosecretory
neurons.
o These axons have their cell bodies in the paraventricular
and supraoptic nuclei of the hypothalamus.
o These neurons secrete:
o antidiuretic hormone
o oxytocin.

Histology of the ParsHistology of the Pars
IntermediaIntermedia
o The pars intermedia
contains large pale
cells that often
surround follicles
filled with ill-defined
"colloid".
o It is small in man,
but much larger in
species such as
amphibians.
o Melanocyte-
stimulating hormone
is the predominant
hormone secreted by
the pars intermedia.

The Hipothalamus Controls PituitaryThe Hipothalamus Controls Pituitary
SecretionSecretion
o Secretion by the anterior
pituitary is controled by
hypothalamic releasing
(RH) and inhibitory
hormones (IH).
o RH ang IH are conducted to
the anterior pytuitary
through minute blood
vesels called hypothalamic-
hypophysial portal vessels.
o Secretion from the posterior
pituitary is controlled by
nerve signals that originate
in the hypothalamus.

Hypothalamic RH and IH ControlHypothalamic RH and IH Control
Anterior Pituitary SecretionAnterior Pituitary Secretion
o Growth hormon releasing
hormone (GHRH)
o Thyreotropin-releasing hormone
(TRH)
o Corticotropin-releasing hormone
(CRH)
o Gonadotropin-releasing
hormone (GnRH)
o Prolactin inhibitory hormone
(PIH)
There are many additional
hypothalamic hormones.
The specific loci of the neuronal
cell body that form the different
RH and IH are still poorly
known.

PituitaryPituitary
HormonesHormones
and Theirand Their
TargetsTargets
o ACTH
o TSH
o GH
o PRL
o FSH
o LH
o MSH
o ADH
o Oxitocin

Function of theFunction of the PPituitaryituitary GGlandland
o Each lobe of the pituitary gland produces certain hormones.
o anterior lobe:
o growth hormone (somatotropin)
o prolactin - to stimulate milk production after giving birth
o ACTH (adrenocorticotropic hormone) - to stimulate the adrenal glands
o TSH (thyroid-stimulating hormone) - to stimulate the thyroid gland
o FSH (follicle-stimulating hormone) - to stimulate the ovaries and testes
o LH (luteinizing hormone) - to stimulate the ovaries or testes
o intermediate lobe:
o melanocyte-stimulating hormone - to control skin pigmentation
o posterior lobe:
o ADH (antidiuretic hormone) - to increase absorption of water into the
blood by the kidneys
o oxytocin - to contract the uterus during childbirth and stimulate milk
production

PatientPatient
o Patient
o Continued

Growth Hormone (Somatotropic Hormone)Growth Hormone (Somatotropic Hormone)
o GH causes growth of almost all tissues.
o GH stimulates cartlage and bone growth.
o GH has multiple metabolic effect:
o increased rate of protein synthesis in most cells
and decrease catabolism
o increased mobilization of fatty acids from
adipose tissue
o increased use of the fatty acids for energy
o decreased rate of glucose utilization
o GH is secreted in pulsatile pattern during
whole life.

The 2-D Structure of Human GHThe 2-D Structure of Human GH
o Growth hormone, also known as
somatotropin, is a protein hormone of
about 190 amino acids that is
synthesized and secreted by cells called
somatotrophs in the anterior pituitary.

GH binding to the MembraneGH binding to the Membrane
o GH circulates in blood
bound to a specific
binding protein,
termed GHBP.
o Signaling and
transduction only
occur when adjacent
receptors bind the
two specific binding
sites on the growth
hormone moiety to
form a dimmer.

Somatomedin (GH/IGF-I) AxisSomatomedin (GH/IGF-I) Axis
o GH causes the liver to form
several small proteins
called sopmatomedins.
o The most important is
somatomedin C (insulin-
like growth factor-I)
o The growth hormone/
insulin-like growth factor-I
axis
o Short duration of action of
GH
o Prolongated action of IGF-I

GH Stimulates GrowthGH Stimulates Growth
o Increased deposit of proteins in
almost all tissue.
o Increased deposit of proteins by
chondrocytic and osteogenic cells.
o GH converts chondrocytes into
osteoblasts.
o GH strongly stimulates the
osteoblasts.
o The thicknes of the epiphyseal
cartilages and the bone increases.

Metabolic Effects of GHMetabolic Effects of GH
o PROTEINS
o increased rate of protein synthesis in most cells
o enhancement of amino acid transport into cells
o enhancemant of RNA translation
o stimulation of transcription of DNA
o decreased catabolism of protein and amino acids
o FAT
o increased mobilization of fatty acids from adipose tissue
o increased use of the fatty acids for energy
o ketogenic effect
o CARBOHYDRATE
o decreased rate of glucoce utilization
o increased glucose production by the liver
o increased insulin secretion
o diabetogenic effects

Factors thatFactors that SStimulate andtimulate and SSuppressuppress
GHGH SSecretionecretion
o Two hypothalamic
hormones regulate
GH secretion:
o Growth Hormone
Releasing Hormone
(GHRH) with a
stimulatory action at
the level of gene
transcription
o Somatostatin (SST)
with an inhibitory
effect on the GH
secretion from the
pituitary gland.

Regulation of GH SecretionRegulation of GH Secretion
o Stimulators
o GHRH
o starvations
o hypoglycemia
o exercise
o stress
o deep sleep
o ghrelin
o Inhibitors
o somatostatin
o obesity
o aging
o hyperglycemia
o somatomedins

Abnormalities of GH SecretionAbnormalities of GH Secretion
o Hypersecretion
o Gigantism (before adolescence)
o Acromegaly (after adolescence)
o Hyposecretion
o Dwarfism (before adolescence)
o Panhypopituitarism in the adults (after
adolescence)

GigantismGigantism
o Overproduction of
GH during
adolescence result
in gigantism.

Acromegalic PatientAcromegalic Patient
o The disease occurs as
a result of excessive
secretion of GH after
adolescence.
o In more than 99% of
cases this is due to a
benign pituitary GH
secreting adenoma.

Posterior PituitaryPosterior Pituitary
o Magnocellular
neurons of the
hypothalamus
secrete
neurohormones
o ADH (vasopressin)
o Oxytocin
o These peptide
hormones are
released into the
blood in the posterior
pituitary.

Hypothalamic Control of PosteriorHypothalamic Control of Posterior
PituitaryPituitary
o Hypothalamus neuron
cell bodies produce:
o ADH: supraoptic nuclei.
o Oxytocin: paraventricular
nuclei.
o Transported along the
hypothalamo-
hypophyseal tract.
o Stored in posterior
pituitary.
o Release controlled by
neuroendocrine
reflexes.

Antidiuretic Hormone (Vasopressin)Antidiuretic Hormone (Vasopressin)
o The single most important
effect of ADH is to conserve
body water by reducing the
output of urine.

Chemical StructureChemical Structure
o Antidiuretic hormone,
also known as
vasopressin, is a nine
amino acid peptide
secreted from the
posterior pituitary.

Physiological Functions of ADHPhysiological Functions of ADH
o ADH stimulates water reabsorbtion by
stimulating insertion of "water
channels" or aquaporins into the
membranes of kidney tubules.
o These channels transport solute-free
water through tubular cells and back
into blood, leading to a decrease in
plasma osmolarity and an increase
osmolarity of urine.

Effects on the Vascular SystemEffects on the Vascular System
o High concentrations of ADH cause
widespread constriction of
arterioles, which leads to increased
arterial pressure.
o In healthy humans, ADH has
minimal pressor effects.

Affect and regulation of ADHAffect and regulation of ADH
o Reduced
urine
volumen
o Water
retention
o Increased
blood
pressure

Regulation of ADH ProductionRegulation of ADH Production
o The most important variable
regulating ADH secretion is plasma
osmolarity, or the concentration of
solutes in blood.
o Osmolarity is sensed in the
hypothalamus by neurons known as
an osmoreceptors.
o Those neurons, in turn, simulate
secretion from the neurons that
produce ADH.

Diabetes InsipidusDiabetes Insipidus
o The most common disease of man and
animals related to ADH is diabetes
insipidus:
o Hypothalamic ("central") diabetes insipidus
results from a deficiency in secretion of ADH.
o Nephrogenic diabetes insipidus occurs when
the kidney is unable to respond to ADH
o The major sign of either type of diabetes
insipidus is excessive urine production.

OxytocinOxytocin
o Oxytocin in a nine
amino acid peptide that
is synthesized in
hypothalamic neurons
and transported down
axons of the posterior
pituitary for secretion
into blood.

Physiologic Effects of OxytocinPhysiologic Effects of Oxytocin
o Stimulation of uterine
smooth muscle
contraction at birth
o Oxytocin is released
during labor when the
fetus stimulates the
cervix, and it enhances
contraction of uterine
smooth muscle to
facilitate parturition or
birth.

Physiologic Effects of OxytocinPhysiologic Effects of Oxytocin
o Stimulation of milk
letdown (milk ejection)
o Establishment of
maternal behavior
o Facilitation of sperm
transport within the male
and female reproductive
system

Control of Oxytocin SecretionControl of Oxytocin Secretion
o The most important stimulus for
release of hypothalamic oxytocin is
initiated by physical stimulation of
the nipples or teats.
o A number of factors can inhibit
oxytocin release, among them acute
stress.

PatientPatient
o SIGNS
o 50-year-old man complaining of impotence
o shoe size had increased
o his friends have remarked on changes in
appearance (the cranium, nose supraorbital
ridges, lower jawbone, hunched back
o the hands develop a size almost twice normal
o his dental plate had to be altered three times in 5
years.
o he was shaving less frequently

PhysicalPhysical and laboratoryand laboratory
examination:examination:
o the hands and feet were enlarged
o the liver, tongue, kidneys and other soft
tissue were enlarged
o visual fields showed a loss of both lateral
(temporal) fields
o the plasma level glucose was 10 mEq/L
o magnetic resonance imaging showed a
large pituitary mass protruded upward
from sella turcica
o increased growth hormone level

Questions:Questions:
o Why did physician measure the growth
hormone?
o The changes in patient’s appearance and
shoe size strongly suggest an excess of
GH.

o What is the cause of hypersecretion of GH?
o Usually a benign acidophilic tumor of
pituitary somatotrophs.

o What is the name of disease?
o Acromegaly

o What has caused the changes in patient’s
feet, hands, liver and facial features?
o GH via somatomedin stimulated
proliferation of chondrocytes, osteoblasts
and connective tissue. The visceral organs
growth is also stimulated.

o The concentration of what peptide is
certainly elevated in patient’s plasma?
o GH stimulates the synthesis of a peptide
mediator called somatomedin in the liver.

o Way is the fasting plasma glucose level
elevated?
o GH is an insulin antagonistic hormone that
inhibits insulin-stimulated glucose uptake
by muscle, fat and the liver. GH decrease
carbohydrate utilization.

o What changes in the plasma insulin level
would you expect to find?
o Plasma insulin levels will be elevated in
response to high glucose levels. GH’s
effects are called diabetogenic.

o What changes do you expect in blood level
of fatty acids?
o GH increase the blood concentration of
fatty acids because release from adipose
tissue. GH enhances fat utilization for
energy. Excessive amount of GH causes
ketosis, fatty liver and atherosclerosis.

o What is the most likely cause of patient’s
impotence?
o A low plasma testosterone level caused by
o direct destruction of gonadotropin-producing
cell by tumour pressure (decrease of LH and
FSH), or
o ablation of hypophyseal stalk (decrease of
GnRH)
o secretion of prolactin by tumours which inhibit
GnRH release

o What has caused the impairment of visual
fields?
o Pressure from tumor on optic nerves cross
causes bitemporal hemyanopsia.

o What is the best therapy?
o microsurgical removal of tumour
o local irradiation
o therapy with somatostatin which can
reduce the elevated GH by inhibiting
receptors on tumors cells.

o If the tmour mass were removed
surgically, what physical changes would
you expect?
o The swelling of soft tissue would resolve
promptly, but the bone changes would
resolve very slowly.
o Also removal the anterior pytuitary gland
would cause permanent deficiencies in
TSH, ACTH, FSH, LH and prolactin.
Replacement therapy with thyroxine and
cortisol would be necessary.

o Would be aldosteron needed?
o No
o Would be prolactin needed?
o No, there are no known consequences of
prolactin deficiency in males.

o How about sexual hormons?
o If the patient wished only to restore
sexual potency, he would require only
testosterone replacement.
o If he still whished to father of child the
treatment with GnRH, or LH and FSH can
be rarely effective.

o Would be ADH needed?
o Removal of posterior pituitary gland would
not ordinarily cause ADH deficiency and
diabetes insipidus. ADH is formed
primarily in the supraoptic nuclei.

QuestionsQuestions??

Hypophysis (Pituitary Gland)

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