Download hypthalamus and pitutary glands

Hypothalamus & Pituitary Gland
The Pituitary Gland and
Hypothalamus
• The pituitary gland
(hypophysis) is located at the
base of the brain, immediately
below the hypothalamus. It is
connected to the hypothalamus
by a pituitary stalk
Dr. M. Alzaharna (2014)
Pituitary-Hypothalamic
relationships
•
The pituitary gland comprises 2 lobes: posterior (neurohypophysis)
and anterior (adenohypophysis)
•
The posterior pituitary is an extension of the
hypothalamus, and consists of neural tissue
– The hormones are synthesised in the
hypothalamus neurons.
– They are transported down the axons
and stored in vesicles in the axon ending
located in the posterior pituitary
– Nerve impulses travel down axons into
the posterior pituitary.
– This causes the release of the vesicles of
hormones into the blood stream at the posterior pituitary
Dr. M. Alzaharna (2014)
Pituitary-Hypothalamic
relationships
• The anterior pituitary has no
direct neural connection to
the brain.
⟶ Blood from the
hypothalamus drains into
capillaries of the anterior
pituitary
⟶ releasing and releaseinhibiting hormones are
carried in the blood to the
anterior pituitary to
regulate hormone release
Dr. M. Alzaharna (2014)
Hormone
Secretion
Morphology
• The pituitary gland (hypophysis) is located in a
small depression in the sphenoid bone, the
sella turcica, just beneath the hypothalamus
• It is connected to the hypothalamus by a thin
stalk called the infundibulum
Sella turcica
Dr. M. Alzaharna (2014)
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Histology of the Anterior Lobe
• Most of the cells in the anterior lobe
(adenohypophysis) contain secretory granules,
although some are only sparsely granulated
• Based on their characteristic staining with
standard histochemical dyes and
immunofluorescent stains, it is possible to
identify the cells that secrete each of the
pituitary hormones
Dr. M. Alzaharna (2014)
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Histology of the Posterior Lobe
• The posterior lobe (neurohypophysis) consists of two
major portions:
– the infundibulum, or stalk,
– and the infundibular process, or neural lobe
• The posterior lobe is richly endowed with fibers
• The cell bodies from which these fibers arise are
located in the hypothalamus
• Secretory material synthesized in cell bodies in the
hypothalamus is transported down the axons and
stored in in the posterior lobe
Dr. M. Alzaharna (2014)
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Physiology of the Posterior Pituitary
• The posterior pituitary gland secretes two
hormones which are:
– oxytocin ,
• increase uterine contractions during parturition
• Contraction of mammary glands to secret milk
– and vasopressin or arginine vasopressin (AVP) (or
Antidiuretic Hormone ‘ADH’)
• contract vascular smooth muscle and thus raise blood
pressure
• promote reabsorption of water by renal tubules
Dr. M. Alzaharna (2014)
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Physiology of the Posterior Pituitary
• Oxytocin and AVP are stored in and secreted
by the posterior pituitary gland, but are
synthesized by the hypothalamus
Dr. M. Alzaharna (2014)
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Regulation of Posterior Pituitary
Function
Regulation of oxytocin secretion showing a
positive feedback arrangement.
Dr. M. Alzaharna (2014)
Increased blood osmolality or decreased blood
volume are sensed in the brain or thorax,
respectively, and increase vasopressin secretion.
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Posterior Pituitary hormones
• The posterior pituitary secretes
two peptide hormones:
⟶ oxytocin (OT)
⟶ antidiuretic hormone (ADH);
also known as vasopressin
Oxytocin
• Stimulates uterine contractions
during childbirth by mobilizing Ca2+
through a second-messenger
system
• Also triggers milk ejection
(“letdown” reflex) in women
producing milk
• Plays a role in sexual function in
males and females
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Antidiuretic Hormone (ADH)
• Osmoreceptors in the hypothalamus
respond to changes in the solute
concentration of the blood plasma
• If solute concentration is high
⟶ Osmoreceptors depolarize and
transmit impulses to hypothalamic
neurons
⟶ ADH is synthesized and released,
inhibiting urine formation by the
kidneys
Physiology of the Anterior Pituitary Gland
• There are six anterior pituitary hormones
whose physiological importance is clearly
established
• They include the hormones that govern the
function of the:
– thyroid and adrenal glands,
– the gonads,
– the mammary glands,
– and bodily growth
Dr. M. Alzaharna (2014)
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Hormones of the Anterior Pituitary Gland
• All the anterior pituitary hormones are
proteins or glycoproteins
• They are divided into 3 categories according to
structure similarity:
– Glycoprotein Hormones
– Growth hormone and prolactin
– Adrenocorticotropin family
Dr. M. Alzaharna (2014)
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Glycoprotein Hormones
Hormone
Thyroid-stimulating
hormone (TSH), also
called thyrotropin
Follicle-stimulating
hormone (FSH)
Target
Major actions in humans
Thyroid gland • Stimulates synthesis and secretion of
thyroid hormones
Ovary
Testis
Luteinizing hormone (LH)
Ovary
Testis
Dr. M. Alzaharna (2014)
• Stimulates growth of follicles and estrogen
secretion
• Acts on Sertoli cells to promote maturation
of sperm
• Stimulates ovulation of ripe follicle
• and formation of corpus luteum;
• stimulates estrogen and progesterone
synthesis by corpus luteum
• Stimulates interstitial cells of Leydig to
synthesize and secrete testosterone
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Growth Hormone and Prolactin
• Somatotropes (GH producing cells) are by far the most
abundant anterior pituitary cells, and account for at
least half the cells
• Structurally, prolactin (PRL) is closely related to GH
Hormone
Target
Growth hormone (GH), also
called somatotropic
hormone (STH)
Most tissues
Major actions in humans




Prolactin
Dr. M. Alzaharna (2014)
Promotes growth in stature and
mass;
stimulates production of insulin-like
growth factor (IGF-I);
stimulates protein synthesis;
usually inhibits glucose utilization
and promotes fat utilization
Mammary glands • Promotes milk secretion and
mammary growth
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Adrenocorticotropin Family
• The ACTH related peptides constitute a family because:
• they contain regions of homologous amino acid sequences,
which may have arisen through exon duplication,
• and because they all are encoded in the same gene
Hormone
Adrenocorticotropic
Target
Adrenal cortex
hormone (ACTH), also
Major actions in humans
• Promotes synthesis and secretion of
adrenal cortical hormones
known as adrenocorticotropin or corticotropin
β-Lipotropin
Adipose
• Physiological role not established
Tissue
Dr. M. Alzaharna (2014)
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Regulation of Anterior Pituitary
Function
• Secretion of the anterior pituitary hormones is regulated by:
– the central nervous system
• provides the primary drive for secretion
– and hormones produced in peripheral target glands
• and peripheral input plays a secondary, though vital, role in
modulating secretory rates
• Secretion of all the anterior pituitary hormones except PRL
declines severely in the absence of stimulation from the
hypothalamus as can be produced
• when the pituitary gland is removed surgically from its natural location
and reimplanted at a site remote from the hypothalamus
– PRL secretion is normally under tonic inhibitory control by the
hypothalamus
Dr. M. Alzaharna (2014)
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Feedback Control of Anterior Pituitary
Function
• Environmental factors may
increase or decrease pituitary
activity by increasing or decreasing
hormone secretions from
hypothalamus
• Pituitary secretions increase the
secretion of target gland
hormones, which may inhibit
further secretion by acting at
either the hypothalamus or the
pituitary
• Pituitary hormones may also
inhibit their own secretion by a
short feedback loop
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•
Anterior Pituitary
hormones
All are proteins
• All except GH activate cyclic AMP
second-messenger systems at their
targets
• TSH, ACTH, FSH, and LH are all tropic
hormones (regulate the secretory
action of other endocrine glands)
Growth Hormone (GH)
• Stimulates cell division targets bone and skeletal
muscle
• Promotes protein synthesis
and encourages use of fats
for fuel
• Most effects are mediated
indirectly by insulin-like
growth factors (IGFs)
Dr. M. Alzaharna (2014)
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Thyroid-Stimulating Hormone
• Produced by the anterior pituitary
• Stimulates the normal
development and secretory
activity of the thyroid
• Regulation of TSH release
⟶ Stimulated by thyrotropin-releasing
hormone (TRH)
⟶ Inhibited by rising blood levels of thyroid
hormones that act on the pituitary and
hypothalamus
Dr. M. Alzaharna (2014)
Adrenocorticotropic Hormone
(ACTH)
• Secreted by the anterior
pituitary
• Stimulates the adrenal cortex to
release cortisol and aldosterone
(to a lesser extent)
• Regulation of ACTH release
⟶ triggered by hypothalamic
corticotropin-releasing hormone
(CRH) in a daily rhythm
⟶ internal and external factors such
as fever, hypoglycaemia, and
stressors can alter the release of CRH
Dr. M. Alzaharna (2014)
Gonadotropins
• Follicle-stimulating
hormone (FSH) and
luteinizing hormone (LH)
secreted by the anterior
pituitary
⟶ FSH stimulates gamete (egg
or sperm) production
⟶ LH promotes production of
gonadal hormones
Dr. M. Alzaharna (2014)
Prolactin (PRL)
• Secreted by the anterior pituitary
• Stimulates milk production
• Regulation of PRL release
– Primarily controlled by prolactininhibiting hormone (PIH)
(dopamine)
• Blood levels rise toward the end of
pregnancy
• Suckling stimulates PRH release and
promotes continued milk production
Dr. M. Alzaharna (2014)
Hypophysiotropic hormones
Hormone
Dr. M. Alzaharna (2014)
Physiological actions of
the pituitary
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Pituitary & Hypothalamic Disorders
• Hypothalamic-pituitary lesions present with a
variety of signs, including pituitary hormone:
– hypersecretion and hyposecretion,
– sellar enlargement,
– and visual loss
Dr. M. Alzaharna (2014)
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Pituitary & Hypothalamic Disorders
• In adults, the most common cause of hypothalamicpituitary dysfunction is a pituitary adenoma, of
which the great majority are hypersecreting
• Thus, the earliest symptoms of such tumors are due
to endocrinologic abnormalities and include:
– Early manifestation
• Hypogonadism, the most frequent
– diminished functional activity of the gonads
– Late manifestation in patients with larger tumors or
suprasellar extension
• sellar enlargement
• headache
• and visual loss,
Dr. M. Alzaharna (2014)
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Gonadotrophins Disorders
• Hyposecretion
– leads to amenorrhoea,
– sterility
– and loss of sexual potency.
– In the young, the sex organs and secondary sexual
characteristics fail to develop (delayed puberty)
• Hypersecretion
– extremely rare,
– in children it could lead to sexual precocity
(excessive premature development)
Dr. M. Alzaharna (2014)
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Thyrotrophin Disorders
• Hyposecretion
– produces a clinical picture similar to primary
thyroid deficiency
• Hypersecretion
– gives the symptoms of hyperthyroidism similar
to Graves’ disease
Dr. M. Alzaharna (2014)
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Corticotrophin Disorders
• Hyposecretion
– rare
– causes failure of cortisol secretion,
– a general lack of health and well being,
– a reduced response to stress and skin
depigmentation
• Hypersecretion
– due to a pituitary microadenoma,
– will result in Cushing’s syndrome
Dr. M. Alzaharna (2014)
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Prolactin Disorders
• Hyposecretion
– leads to failure of lactation in women
• Hypersecretion
– may result from a pituitary tumour
– principal symptoms are infertility and menstrual
complaints
– in men, decreased libido,
– inadequate sperm production and impotence,
whereas in women, there may be a complete lack
of menstruation
– inappropriate (non-pregnant) milk production
Dr. M. Alzaharna (2014)
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GHRH Disorders
• Hyposecretion
– caused by hypothalamic or pituitary dysfunction
– In childhood this leads to impairment of
growth (dwarfism)
• Hypersecretion
– This usually results from a benign pituitary tumour
– In young patients, this leads to gigantism
– In adults, leads to acromegaly
Dr. M. Alzaharna (2014)
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Vasopressin Disorders
• Hyposecretion
– caused by damage or dysfunction of the
hypothalamus,
– can lead to diabetes insipidus,
• excessively large amounts of dilute urine (10–15
liters/day) are produced by the kidneys
• Hypersecretion
– rare condition of inappropriate AVP production is
known as syndrome of inappropriate ADH (SIADH)
Dr. M. Alzaharna (2014)
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Hypopituitarism
• Hypopituitarism is manifested by diminished
or absent secretion of one or more pituitary
hormones
• Hypopituitarism is either:
– a primary event
• caused by destruction of the anterior pituitary gland
– or a secondary phenomenon
• resulting from deficiency of hypothalamic stimulatory
factors normally acting on the pituitary
Dr. M. Alzaharna (2014)
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Assessment of Target
Gland Function
• If endocrine hypofunction is
suspected, pituitary hormone
deficiencies must be distinguished
from primary failure of the thyroid,
adrenals, or gonads
• Baseline laboratory studies should
include:
– thyroid function tests (free T4)
– and determination of serum
testosterone levels
• Testosterone is a sensitive indicator
of hypopituitarism in women as well
as in men
Dr. M. Alzaharna (2014)
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• In primary target gland hypofunction, such as
autoimmune polyglandular syndromes types 1
and 2 (APS 1 and 2), TSH, LH, FSH, or ACTH will
be elevated
• Low or normal values for these pituitary
hormones suggest hypothalamic-pituitary
dysfunction
Dr. M. Alzaharna (2014)
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