Download Hypothalamus and Pituitary

Hypothalamus and Pituitary
Hypothalamus and Pituitary
• The hypothalamus-pituitary unit is the most
dominant portion of the entire endocrine
system.
• The output of the hypothalamus-pituitary
unit regulates the function of the thyroid,
adrenal and reproductive glands and also
controls somatic growth, lactation, milk
secretion and water metabolism.
Hypothalamus and Pituitary
• Pituitary function depends on the hypothalamus
and the anatomical organization of the
hypothalamus-pituitary
unit
reflects
this
relationship.
• The pituitary gland lies in a pocket of bone at the
base of the brain, just below the hypothalamus to
which it is connected by a stalk containing nerve
fibers and blood vessels.
The pituitary is
composed to two lobes-- anterior and posterior
Posterior Pituitary:
neurohypophysis
• Posterior pituitary: an outgrowth of the
hypothalamus composed of neural tissue.
• Hypothalamic neurons pass through the
neural stalk and end in the posterior
pituitary.
• The upper portion of the neural stalk
extends into the hypothalamus and is called
the median eminence.
Anterior pituitary:
adenohypophysis
• Anterior pituitary: connected to the
hypothalamus by the superior hypophyseal artery.
• The antererior pituitary is an amalgam of hormone
producing glandular cells.
• The anterior pituitary produces six peptide
hormones: prolactin, growth hormone (GH),
thyroid stimulating hormone (TSH),
adrenocorticotropic hormone (ACTH), folliclestimulating hormone (FSH), and luteinizing
hormone (LH).
Hypothalamus and pituitary gland
Hypothalamus and pituitary gland
Regulation
of
Hypothalamus
Anatomical and functional
organization
Hypothalamic releasing factors for
anterior pituitary hormones
 Travel to adenohypophysis via hypophyseal-portal
circulation
 Travel to specific cells in anterior pituitary to
stimulate synthesis and secretion of trophic
hormones
Hypothalamic releasing hormones
Hypothalamic releasing hormone
Effect on pituitary
Corticotropin releasing hormone
(CRH)
Thyrotropin releasing hormone
(TRH)
Growth hormone releasing
hormone (GHRH)
Somatostatin
Stimulates ACTH secretion
Gonadotropin releasing hormone
(GnRH)
Prolactin releasing hormone (PRH)
Prolactin inhibiting hormone
(dopamine)
Stimulates TSH and Prolactin
secretion
Stimulates GH secretion
Inhibits GH (and other hormone)
secretion
Stimulates LH and FSH
secretion
Stimulates PRL secretion
Inhibits PRL secretion
Characteristics of hypothalamic
releasing hormones
•
•
•
•
•
•
Secretion in pulses
Act on specific membrane receptors
Transduce signals via second messengers
Stimulate release of stored pituitary hormones
Stimulate synthesis of pituitary hormones
Stimulates hyperplasia and hypertophy of target
cells
• Regulates its own receptor
Anterior pituitary
• Anterior pituitary: connected to the
hypothalamus by hypothalmoanterior pituitary
portal vessels.
• The anterior pituitary produces six peptide
hormones:
–
–
–
–
–
prolactin, growth hormone (GH),
thyroid stimulating hormone (TSH),
adrenocorticotropic hormone (ACTH),
follicle-stimulating hormone (FSH),
luteinizing hormone (LH).
Anterior pituitary cells and
hormones
Hypothalamus
and anterior
pituitary
Anterior pituitary hormones
Feedback regulation of
hypothalmus/pituitary
• A prominent feature of each of the
hormonal sequences initiated by the
hypothalamic releasing hormones is
negative feedback exerted upon the
hypothalamic-pituitary system by the
hormones whose production are stimulated
in the sequence.
Hypothalamus-pituitary axis
Feedback control
Feedback
control of
thyroid
function
Feedback and
restoration of
homeostasis
Feedback
control of
growth
hormone
Growth hormone vs. metabolic state
• When protein and energy intake are adequate, it is
appropriate to convert amino acids to protein and stimulate
growth. hence GH and insulin promote anabolic reactions
during protein intake
• During carbohydrate intake, GH antagonizes insulin
effects-- blocks glucose uptake to prevent hypoglycemia.
(if there is too much insulin, all the glucose would be taken
up).
• When there is adequate glucose as during absorptive
phase, and glucose uptake is required, then GH secretion is
inhibited so it won't counter act insulin action.
Growth hormone vs. metabolic
state
• During fasting, GH antagonizes insulin action and helps
mediate glucose sparing, ie stimulates gluconeogenesis
• In general, duing anabolic or absorptive phase, GH
facilitates insulin action, to promote growth.
• during fasting or post-absorptive phase, GH opposes
insulin action, to promote catabolism or glucose sparing
Growth
hormone
and
metabolic
state
ACTH: adrenocorticotropic hormone:
synthesis and regulation of secrtion
• Produced in corticotrophs
• ACTH is produced in the anterior pituitary by
proteolytic processing of Prepro-opiomelanocortin
(POMC).
• Other neuropeptide products include b and g
lipotropin, b-endorphin, and a-melanocytestimulating hormone (a-MSH).
• ACTH is a key regulator of the stress response
ACTH synthesis
ACTH
ACTH is made up of 39 amino acids
Regulates adrenal cortex and synthesis of
adrenocorticosteroids
a-MSH resides in first 13 AA of ACTH
a-MSH stimulates melanocytes and can darken
skin
Overproduction of ACTH may accompany
increased pigmentation due to a-MSH.
Addison’s Disease
• Disease in which patients lack cortisol from
zona fasiculata, and thus lacks negative
feedback that suppresses ACTH production
• Result: overproduction of ACTH
• Skin color will darken
• JFK had Addison’s disease and was treated
with cortisol injections
b-endorphin
•
•
•
•
Produced as a result of ACTH synthesis
Binds to opiate receptors
Results in “runner’s high”
Role in anterior pituitary not completely
understood
• One of many endogenous opiods such as
enkephalins
Regulation
of ACTH
secretion
Regulation of ACTH
• Stimulation of release
– CRH and ADH
– Stress
– Hypoglycemia
• CRH and ADH both synthesized in hypothalamus
– ADH is released by posertior pituitary and reaches
anterior pituitary via inferior hypophyseal artery.
ACTH
• Circadian pattern of release
– Highest levels of cortisol are in early AM
following ACTH release
– Depends on sleep-wake cycle, jet-lag can result
in alteration of pattern
• Opposes the circadian pattern of growth
hormone secretion
Regulation
of ACTH
ACTH
• Acts on adrenal cortex
– stimulates growth of cortex (trophic action)
– Stimulates steroid hormone synthesis
• Lack of negative feedback from cortisol results in
aberrantly high ACTH, elevated levels of other
adrenal corticosteroids– adrenal androgens
• Adrenogenital syndrome: masculization of female
fetus
Glycoprotein hormones
LH, FSH, TSH and hCG
a and b subunits
Each subunit encoded by different gene
 a subunit is identical for all hormones
 b subunit are unique and provide biological
specificity
Glycoprotein hormones
Glycoprotein hormones contain two subunits, a
common a subunit and a distinct b subunit:
TSH, LH, FSH and hCG.
Gonadotrophs
• Cells in anterior pituitary that produce LH and
FSH
• Synthesis and secretion stimulated by GnRH–
major effect on LH
• FSH secretion controlled by inhibin
• Pulsitile secretion of GnRH and inhibin cause
distinct patterns of LH and FSH secretion
LH/FSH
• Pulsatile pattern of secretion
– LH pulses are biphasic (every 1 minute, then large
pulse at 1 hour)
– FSH pulses are uniphasic
• Diurnal– LH/FSH more pronounced during
puberty
• Cyclic in females– ovarian cycle with LH surge at
time of ovulation
• Males are not cyclic, but constant pulses of LH
cause pulses of testosterone to be produced
Pulsitile secretion of GnRH and LH
Regulation of LH/FSH
• Negative feed-back
– Inhibin produced by testes and ovaries Decreases FSH
b-subunit expression
– Testosterone from Leydig cells– synthesis stimulated by
LH, feedsback to inhibit GnRH production from
hypothalamus and down-regulates GnRH receptors
– Progesterone– suppresses ovulation, basis for oral
contraceptives. Works at both the level of pituitary and
hypothalamus.
Regulation of LH/FSH
• Dopamine, endorphin, and prolactin inhibit GnRH
release.
– Prolactin inhibition affords post-partum contraceptive
effect
• Overproduction of prolactin via pituitary tumor
can cause amenorrhea– shuts off GnRH
– Treated with bromocryptine (dopamine agonist)
– Surgical removal of pituitary tumor
Regulation of LH/FSH
• Positive feedback
– Estradiol at high plasma concentrations in late
follicular phase of ovarian cycle stimulates
GnRH and LH surge– triggers ovulation
Regulation of
gonadotropin
secretion
Thyrotrophs
•
•
•
•
Site of TSH synthesis
Pattern of secretion is relatively steady
TSH secretion stimulated by TRH
Feedback control by T3 (thyroid hormone)
Feedback
control of
thyroid
function
Lacotrophs
• Site of production of prolactin
• Lactogenesis (milk synthesis) requires prolactin
• Tonically inhibited
– Of the anterior pituitary hormones, the only one
– Multifactoral control, balance favors inhibition
• Dopamine inhibits prolactin
• Prolactin releasing hormone is TRH
– Ocytocin also stimulates prolactin release
– Estradiol enhances prolactin synthesis
Prolactin
• Stimulates breast development and
lactogenesis
• May be involved in development of Leydig
cells in pre-pubertal males
• Immunomodulatory effects– stimulates T
cell functions
– Prolactin receptors in thymus
Posterior pituitary hormones: ADH
(AVP) and Oxytocin (really
hypothalamic hormones)
 Both are synthesized in the cell bodies of
hypothalamic neurons
 ADH: supraoptic nucleus
 Oxytocin: paraventricular nucleus
 Both are synthesized as preprohormones and
processed into nonapeptides (nine amino acids).
 They are released from the termini in response to
an action potential which travels from the axon
body in the hypothalamus
Hypothalamus and posterior
pituitary
Structures of ADH and oxytocin
Oxytocin: stimulates
myoepithelial contractions
In uterus during parturition
In mammary gland during
lactation
Oxytocin: milk ejection from
lactating mammary gland
suckling is major stimulus for
release.
sensory receptors in nipple connect
with nerve fibers to the spine, then
impulses are relayed through brain
to PVN where cholinergic synapses
fire on oxytocin neurons and
stimulate release.
Oxytocin: uterine contractions
• Reflexes originating in the cervical, vaginal
and uterus stimulate oxytocin synthesis and
release via neural input to hypothalamus
• Increases in plasma at time of ovulation,
parturition, and coitus
• Estrogen increases synthesis and lowers
threshold for release
Oxytocin secretion is stimulated
by nursing
ADH: conserve body water and
regulate tonicity of body fluids
Also known as vasopressin
Regulated by osmotic and volume
stimuli
Water deprivation increases
osmolality of plasma which activates
hypothalmic osmoreceptors to
stimulate ADH release
Regulation of
ADH secretion
ADH increases renal tubular
absorption of water
ADH and
plasma
osmolality
ADH
and
blood
pressure