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 and
lipotropin, -endorphin, and -melanocytestimulating hormone (-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
-MSH resides in first 13 AA of ACTH
-MSH stimulates melanocytes and can darken
skin
Overproduction of ACTH may accompany
increased pigmentation due to -MSH.

Addisons 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 Addisons disease and was treated
with cortisol injections

-endorphin

Produced as a result of ACTH synthesis

Binds to opiate receptors
Results in runners 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
and subunits
Each subunit encoded by different gene
subunit is identical for all hormones
subunit are unique and provide biological

specificity

Glycoprotein hormones
Glycoprotein hormones contain two subunits, a
common subunit and a distinct 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
-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