week 4, lecture 1 Flashcards
- Which of the following hormones is released from the posterior pituitary?
- A. TSH
- B. ADH
- C. CRH
- D. Somatostatin
- B. ADH
also oxytocin
- Prolactin is produced by which of the following cell type?
- A. Thyrotrope
- B. Gonadotrope
- C. Lactotrope
- D. Somatotrope
- C. Lactotrope
what are the two embryological regions that form the pituitary?
rathe pouch and infundibular process
what is the posterior pituitary formed from?
infundibular process
what is the anterior pituitary formed from?
ranthke pouch
what is the rathe pouch and what does it form?
outgrowth from the stomodeum (primitive mouth) that grows upwards towards the developing hypothalamus (part of diencephalon)
- Forms the anterior pituitary
what is the infundibular process and what does it form?
▪ Infundibular process – inferior outgrowth from the developing
hypothalamus
- Forms rest of the pituitary (posterior pituitary) and infundibular stalk
where is the pituitary found in the brain?
hypophyseal fossa, surrounded by bone (sella turcica) and close to optic chiasm
magnocellular neuron vs parvicellular neuron; which is posterior and anterior pituitary
magnocellular= posterior
parvicellular= anterior
how magnocellular neurons work to go to posterior pituitary?
- Magnocellular neurons transport peptide hormones from the cell body (fast axonal transport) to their axon terminals in the posterior pituitary
▪ Released into the capillary plexus formed by the inferior hypophyseal artery
▪ Hormones from magnocellular neurons need to be released in adequate concentrations to impact tissues throughout the body
▪ Major hypothalamic nuclei – PVN, SON
what are the hypothalamic nuclei for magnocellular neurons?
PVN and SON
what does PVN and SON secrete
▪ The PVN secretes mostly oxytocin, with a bit of ADH
▪ The SON secretes mostly ADH, with a little oxytocin
what does PVN secrete
mainly oxytocin, some ADH
what does SON secrete
mostly ADH, some oxytocin
what are the 2 hormones secreted by posterior pituitary
ADH/ vasopressin and oxytocin
what is ADH purpose
▪ The major regulator of water content in our body
▪ Can also cause vasoconstriction
what is oxytocin for?
- Oxytocin is a key hormone in the milk letdown reflex and in the augmentation of labour
what are the 2 receptors/ stimuli for release of the posterior pituitary ADH hormone ?
osmoreceptors and baroreceptors
how do osmoreceptors work and which hormone are they a major stimulus for?
Osmoreceptors in the hypothalamus and in the lamina terminalis detect osmolarity of the extracellular fluid
▪ This is the major stimulus for ADH release
▪ in response to decreased osmolarity ! osmoreceptors shrink ! stimulate magnocellular neurons in the PVN/ SON! ADH release
where are baroreceptors found and what are they in response of?
(carotid sinus, aortic arch, or atria)
▪ In response to decreased BP ! cells in the carotid sinus are stimulated ! communication with the PVN/ SON via the brainstem
▪ Can also be stimulated by decreases in blood volume – as blood volume decreases ! less stretch at the atria ! release of ADH
osmoreceptors and baroreceptors stimulate by? what they release?
osmo- osmolarity
baro- blood pressure and blood volume
both release ADH
where are baroreceptors
carotid sinus, aortic arch, or atria
where are osmoreceptors
hypothalamus and in the lamina terminalis
adenohypophysis vs neurohypophysis
which is anterior and pituitary
Adeno= anterior
neuro= posterior
anterior vs posterior pituitary
Anterior-
adenohypophysis
endocrine
epitheilial tissue
Posterior-
neurohypophysis
neural tissue extension originating in the brain
pituitary gland anatomy
Structure- lima-bean sized gland connected to the brain by an infundibulum
Situated in the Sella Tursica (Sphenoid bone)
2 lobes- anterior and posterior
Situated below both the Hypothalamus and the Optic Chiasm
SON
supraoptic neurons
PVN
paraventricular neurons
vascular or neural connection between hypothalamus and the posterior and anterior pituitary
Vascular connection between Hypothalamus and Anterior Pituitary
Neural connection between Hypothalamus and Posterior Pituitary
innervation of pituitary
Sympathetic/Parasympathetic
what are the 2 hypothalamic nuclei that project axons into posterior pituitary
Supraoptic SON
Paraventricular PVN
what is the vascular supply for posterior pituitary?
Hypophyseal portal system
concentrated neurohormones are secreted into a capillary network and affect target organs through the blood supply
Significance: smaller amounts can be secreted and have a potent effect
what is the hormone secreted from each of the following cell types
somatotrope
lactotrope
corticotrope
thyrotrope
gonadotrope
somatotrope- growth hormone
lactotrope- prolactin
corticotrope- ACTH
thyrotrope- TSH
gonadotrope- LH, FSH
embryonic organs of posterior pituitary
Evagination of the Third Ventricle
embryonic origins of anterior pituitary
Rathke pouch- evagination of the roof of the pharynx
embryonic origins of posterior and anterior pituitary
Posterior Pituitary
Evagination of the Third Ventricle
Anterior Pituitary
Rathke pouch- evagination of the roof of the pharynx
what are the 6 hormones in anterior pituitary?
Prolactin, TSH, GH, FSH, LH, ACTH
how is secretion in the anterior pituitary controlled?
Secretion is controlled by hypophysiotropic hormones
SLIDE 31 diagram
xx
posterior pituitary: 2 hormones and functions
Stores and releases 2 hormones
ADH (Vasopressin)- water balance
Oxytocin- milk ejection and uterine contractions
oxytocin 2 primary functions
Milk ejection: triggers milk ejections from mammary glands during chest feeding
Uterine contractions: helps during childbirth to support labour and delivery
–> both of these are smooth muscle contraction
Role in social bonding between individuals
how does oxytocin do contraction of smooth muscle?
▪ Receptor activation–> Gq-mediated increases in cytosolic calcium and activation of smooth muscle myosin (see next slide)
▪ Calcium excites smooth muscle using different molecular mechanisms than in skeletal or cardiac muscle
what type of feedback is oxytocin?
positive feedback
like the uterus is slowly being “primed” until secretion of oxytocin is enough to bring about the positive feedback cycle of uterine contraction and cervical thinning/dilation
what stimulates oxytocin release?
sensory stimulation of breast tissue (milk ejection) or pressure/thinning of the cervix (in pregnancy)
when does oxytocin work in pregnancy?
- Oxytocin does not exert its effect on uterine tissue until it is time for parturition (too early ! premature labour)
what does oxytocin do at the end of pregnancy? what hormones also increase at the same time?
▪ The uterus increases gap junctions and oxytocin receptors at the end of pregnancy
- Steadily increasing levels of estrogen ! more oxytocin receptors
- prostaglandin levels within the uterus also rise later in pregnancy (regulation poorly-understood) – prostaglandins also aid uterine contraction
what regulates (inhibits and then gets lifted) oxytocin secretion in the brain?
▪ Most of the time, significant secretion of oxytocin during pregnancy is inhibited by input from other brain regions
- Neurotransmitters of interest include GABA, NO, endogenous opioids
▪ This inhibition is lifted near the end of pregnancy, when estrogen levels rise and progesterone levels begin to decline
what other factors inhibit oxytocin secretion
- “stressors” – fear, pain, loud noise
- fever
ADH (Anti-diuretic Hormone) is aka
vasopression
primary function of ADH
Water regulation- acts on kidneys to increase water reabsorption
results in decreased urine production—> prevents dehydration
water balance maintenance—> blood osmolarity maintained
what is ADH stimulated by?
▪ increased ECF osmolarity – most powerful stimulator, detected by osmoreceptors near the hypothalamus in the lamina terminalis
▪ decreased blood pressure/volume – weaker stimulus, detected at arterial baroreceptors and venous baroreceptors (venous found in great vessels, atrial walls)
what 2 receptors does ADH work on?
V1 and V2
what are the 2 major effects of ADH
▪ V1 receptor activation in vascular smooth muscle !
vasoconstriction and increased BP
▪ V2 receptor activation in the kidney ! increased water reabsorption! increased extracellular fluid volume (and decreased osmolarity) and more concentrated (and lower volume) urine
ADH on V1 receptor does…
increase BP
ADH on V2 receptor does…
decrease osmolarity
why are pituitary adenomas so common?
▪ They are all monoclonal, so likely a mutation confers a
growth advantage
▪ Some have activating mutations in Gs-proteins (1/3)
▪ Some seem to over-express or over-activate growth factor signaling (FGF or EGF)
▪ Loss of negative feedback inhibition (increased hypothalamic releasing hormone) may play a role…
- Rare familial syndromes (to cover with NPLEX review course) such as multiple endocrine neoplasia (MEN) involve loss of tumour suppressor genes
chart for pituitary tumors
slide 42
involves lots of hypogonadism, …
what is the most common adenoma?
lactotroph adenoma (prolactin effected)
what is hypopituitarism (from tumor)
▪ Hypopituitarism – compression of functional anterior pituitary
tissue
- Exception – often results in excessive function of lactotrophs – why?
- Impingement and loss of normal pituitary function are usually early manifestations of expansion
- The posterior pituitary stalk can also be compressed –> diabetes insipidus
bitemporal hemianopsia (from tumor)
as it elevates the dura and “crushes” the lateral optic nerves
- Scotomas, blindness, and loss of red perception can also occur – everyone with a pituitary tumour needs a thorough eye exam
- Ophthalmoplegia and facial numbness can also occur as the cavernous sinus is impacted (CN III, CN IV, CN VI)
common effects of pituitary tumors
- hypopituitarism
- bitemporal hemianopsia (visioN)
- headache
lactotroph adenomas? clinical presentation?
Lactotroph adenomas are the most common cause of hyperprolactinemia with high levels of PRL (prolactin)
most common adenoma
Presentation: amenorrhea, galactorrhea, loss of libido, and infertility
▪ Why amenorrhea & infertility? PRL inhibits GnRH secretion and directly impairs gonadal steroid production
- In men, can lead to low testosterone levels, loss of fertility, and loss of libido (galactorrhea is uncommon)
what are functional disorders of the pituitary?
result from hormone-secreting tumours – eg adenoma (can be micro or macro)
Can lead to overproduction of hormones causing concerns like
GH- Giantism (children) and Acromegaly (adults)
PRL- Prolactinoma (most common ~50%)
symptoms from functional disorders of pituitary?
Symptoms from mass effects include headache; visual loss through compression of the optic chiasm (classically a bitemporal hemianopia); and diplopia, ptosis, ophthalmoplegia, and decreased facial sensation from cranial nerve compression laterally.
Pituitary stalk compression from the tumour may also result in mild hyperprolactinemia. Symptoms of hypopituitarism or hormonal excess may be present as well (see below).
what are non-functional tumors and hypopituitarism
do not secrete hormones- about 1/3
Can lead to hypopituitarism- insufficient hormone production
As a result, can affect other hormones resulting in various symptoms
ACTH- adrenal insufficiency- fatigue, weight loss, LBP
TSH- hypothyroidism symptoms
FSH and LH- sexual dysfunction and infertility
functional vs non functional tumors
functional- secrete horomones (i.e. prolactinoma, gigantism)
nonfunctional- dont secrete hormones (i.e. hypothyroid, adrenal insufficeincy)
hyperpituitarism
increased hormone production
causes of hypopituitarism (low levels of pituitary hormones)
genetic,
congenital,
traumatic (pituitary surgery, cranial irradiation, head injury),
neoplastic (large pituitary adenoma, parasellar mass, craniopharyngioma, metastases, meningioma),
infiltrative (hemochromatosis, lymphocytic hypophysitis, sarcoidosis, histiocytosis X),
vascular (pituitary apoplexy, postpartum necrosis, sickle cell disease), or
infectious (tuberculous, fungal, parasitic).
findings for GH in hypopituitarism
growth disorders in children; increased intraabdominal fat, reduced lean body mass, hyperlipidemia, reduced bone mineral density, decreased stamina, and social isolation in adults
findings for FSH/LH in hypopituitarism
menstrual disorders and infertility in women, hypogonadism in men
findings for ACTH in hypopituitarism
features of hypocortisolism without mineralocorticoid deficiency
findings for TSH in hypopituitarism
growth retardation in children; features of hypothyroidism in children and adults
findings for PRL (prolactin) in hypopituitarism
failure to lactate postpartum
what is the sequence in which hormones are effected in hypopituitarism
GH>FSH>LH>TSH>ACTH
which hormone is effected first in hypopituitarism
GH
releasing hormones vs stimulating hormones
releasing are in hypothalamus ie. CRH
stimulating in pituitary ie. FSH (anterior p)
HPG axis (hypothalamus- pituitary gonadal axis)
hypothalamus (GnRH) –> anterior pituitary (LH and FSH) –>
men: testes (testosterone)
women: ovaries (estrogen and progesterone)
- If a patient presents with reduced bone mineral density, increased abdominal fat and decreased stamina with some possible depression, following a recent head injury – which of the following would be reasonable mechanisms to explain this presentation?
- A. Increased prolactin secretion secondary to prolactinoma
- B. Trauma to the somatotropes of the anterior pituitary
resulting in hypopituitarism - C. TSH-secreting adenoma resulting in suppression of TRH and subsequent hypopituitarism
- D. Side effect of starting a new antidepressant resulting in hyperprolactinemia
- B. Trauma to the somatotropes of the anterior pituitary
resulting in hypopituitarism
anterior pituitary is derived from
endothelial tissue
posterior pituitary is a ___ extension
neural
Anterior and posterior release how many hormones
6 and 2
hypopituitarism causes
genetic, traumatic, congenital and neoplastic
