Hypothalamic Pituitary Axis Flashcards
what are the 3 axes of the endocrine system and what do they regulate the function of?
a. Hypothalamic-pituitary unit regulates the fcn of thyroid, adrenal and gonads
i. HPT axis
ii. HPA axis
iii. HPG axis (male, female)
what do the axes control?
i. Growth
ii. Milk production, ejection
iii. Osmoregulation
parts of the pituitary gland and the embryological derivatives
a. Pituitary gland—hypophysis
b. Composed of:
i. Anterior pituitary—adenohypophysis
1. Epithelial portion from oral ectoderm
ii. Posterior pituitary—neurohypophysis
1. Neural portion from neural ectoderm
c. Hypophyseal stalk—physical connection b/w the hypothalamus and the pituitary gland
d. Generally, cancers of the pituitary expand up into the brain and against the optic Ns
i. Inc in pituitary size often associated with dizziness and vision problems
nuclei of the posterior pituitary
a. Posterior pituitary is a collection of axons whose cell bodies are located in the hypothalamus
i. Supraoptic nucleus—releases primarily ADH
ii. Paraventricular nucleus—releases primarily oxytocin
1. When AP from here, it causes release of ADH and oxytocin
relationship b/w the hypothalamus and anterior lobe of pituitary
a. is both neural and hormonal
Hs secreted by the anterior pituitary
- Thyroid stimulating H (TSH)
- Follicle stimulating H (FSH)
- Luteinizing H (LH)
- Growth H
- Prolactin
- Adrenocorticotropic H (ACTH)
how is anterior pituitary connected to the hypothalamus and how do Hs move from one to the other?
i. Connected to the hypothalamus by the hypothalamic-hypophysial portal vessels
1. Hypothalamic Hs can be delivered to the anterior pituitary directly and in high concentration
2. The hypothalamic Hs do not appear in the systemic circulation in high concentration
Hypothalamic hypophysiotropic neurons are often …
a. secreted in pulsatile manner and are entrained to circadian rhythms
primary endocrine disorder
low or high levels of H due to defect in the peripheral endocrine gland (in a target tissue)
secondary endocrine disorder
low or high levels of H due to defect in the pituitary gland
tertiary endocrine disorder
a. low or high levels of H due to defect in the hypothalamus
what kind of Hs are secreted from anterior pituitary?
peptide
corticotrophs
secrete ACTH after being stimulated by CRH
thyrotroph
secrete TSH after being stimulated by TRH
gonadotroph
secrete LH and FSH after being stimulated by GnRH
somatotroph
secrete GH after stimulation by GHRH
inhibited by somatostatin
lactotroph
secrete prolactin after being stimulated by TRH
inhibited by PIF (dopamine
melanocyte stimulating H
i. ACTH family
1. ACTH has melanocyte stimulating H activity
a. Increase in blood levels of MSH containing fragments can cause skin pigmentation
Addison’s Disease*
ACTH levels increase, and skin pigmentation is a symptom of this disorder
what is a major regulator of the HPA axis?
a. Stress is a regulator of the HPA axis
i. Sources of stress:
1. Neurogenic—fear
2. Systemic—infection, surgery
ii. Hypothalamus has the ability to reset the set point in response to stress
HPT axis
a. TSH is released by thyrotrophs in the anterior pituitary
i. TSH is a glycoprotein H
b. TSH is under the stimulatory control of the hypothalamus
i. Stimulated by the release of TRH from parvicellular hypothalamic neurons
c. TSH stimulates the thyroid gland
d. Stress (physical stress, starvation, infection) inhibits TRH secretion
HPG axis
a. FSH and LH are released by gonadotrophs in the anterior pituitary
i. Secreted into secretory granules allowing independent secretion by gonadtrophs
b. FSH and LH are under the stimulatory control of the hypothalamus
i. GnRH
c. FSH and LH regulate the function of gonads in males and females stimulates the thyroid gland
d. Prolactin, stress, opioids inhibit the axis
e. Inhibin inhibits action of the pituitary gland gonadotrophs
stimulus and inhibition of GH secretion
a. Stimulus from the release of GHRH from the hypothalamus
b. Inhibition from the release of somatostatin from hypothalamus
i. Both then go to anterior pituitary
somatomedins
are formed from the target tissues stimulated by GH and these work in the negative feedback loop
how is GH secreted?
a. pulsatile secretion is done for growth H with a burst of secretion occurring every 2 hours
b. GH is secreted throughout life with levels increasing through puberty then dropping down until senescence
direct and indirect effects of GH
- Direct: effect on target tissues—skeletal muscle, liver, adipose tissue
- Indirect: mediated by the production of somatomedins in the liver—IGF-1
metabolic actions of GH
- Diabetogenic effect—increase in blood glucose concentration
a. Causes insulin resistance
b. Decrease glucose uptake and utilization by target tissues
c. Increase lipolysis in adipose tissue
d. Results in increase in blood insulin levels - Increase protein synthesis and organ growth
a. Increase uptake of AAs
b. Stimulates synthesis of DNA, RNA, and protein
c. Mediated by somatomedins - Increase linear growth
a. Stimulates synthesis of DNA, RNA, and protein
b. Mediated by somatomedins
c. Increase metabolism in cartilage forming cells and chondrocytes proliferation
GH deficiency*
- Decrease secretion of GHRH (due to hypothalamic dysfunction)
- Decrease GH secretion (secondary deficiency)
- Failure to generate somatomedins
- GH or somatomedin resistance (deficiency of Rs)
GH deficiency in children is treated with human GH replacement
GH excess
-acromegaly
- Mostly due to a GH secreting pituitary adenoma
- Consequences depend on development stage:
a. Before puberty–>gigantism
b. After puberty–>inc periosteal bone growth, increase organ size, increase extremity size, coarsening of the facial features, insulin resistance, and glucose tolerance
c. Conditions with excess secretion of GH are treated with somatostatin analogues—octreotide
i. Inhibits GH secretion
regulation of prolactin secretion
a. Whenever woman is not lactating, then dopamine is the reason that prolactin is not secreted to cause lactation
b. Dopamine release:
i. From hypothalamus and down to median eminence and then the anterior pituitary
ii. From the posterior pituitary and then thru blood to anterior pituitary
iii. From lactotrophs—autocrine regulation
prolactin and breast development
i. combined actions with progesterone and estrogen
1. At puberty—stimulate proliferation and branching of mammary ducts
2. During pregnancy—stimulates growth and development of the mammary alveoli in preparation for lactation
prolactin and lactogenesis
i. induces the synthesis of lactose, casein, and lipids which are enzymes needed for the production of milk
1. Although prolactin levels are high during pregnancy, lactation doesn’t occur b/c high levels of estrogen and progesterone down regulate prolactin Rs
2. At birth, the inhibition is released when estrogen and progesterone levels drop precipitously, when this occurs lactogenesis is stimulated
a. So during pregnancy, lactogenesis is not stimulated b/c estrogen/progesterone levels were high
prolactin and
suppression of ovulation
- Inhibits synthesis and secretion of GnRH
prolactin deficiency
- Results in inability to lactate
- Causes: destruction of the anterior love of the pituitary or selective destruction of the cells that secrete prolactin (lactotrophs)
prolactin excess
- Results in:
a. Galactorrhea—excessive milk production
b. Infertility—caused by inhibition of GnRH secretion by prolactin - Causes:
a. Destruction of hypothalamus or interruption of the hypothalamic-hypophysela tract—results in loss of tonic inhibition by dopamine
b. Prolactinoma—prolactin secreting tumors
c. Bromocriptine (dopamine R agonist) can be used for the tx of prolactin excess
panhypopituitarism
a. Panhypopituitarism is a condition of inadequate or absent production of the anterior pituitary Hs
b. Causes: problems that affect the pituitary gland and either reduce or destroy its fcn or interfere with hypothalamic secretion of the varying pituitary releasing H
i. Brain damage—traumatic brain injury, subarachnoid hemorrhage, irradiation, stroke
ii. Pituitary tumors—adenomas
pituitary adenomas
- Pituitary adenomas—most pituitary tumors are these
a. Most occur spontaneously
b. Classified according to:
i. Size:
1. Microadenoma: 1 cm
ii. Aggressiveness
1. Nearly all pituitary adenomas are benign and slow growing
iii. Hormone secretion:
1. Functional tumors: adenomas that release an active H, usually an excessive amt
2. Clinically non functioning adenoma: do not release active H
a. H producing pituitary adenomas release an active H in excessive amounts in the bloodstream
what usually results?
- Prolactinoma—(60%), a tumor that overproduces prolactinassociated with hypogonadism and galactorrhea
- Acromegaly (adults) and gigantism (children)—caused by an excess GH (20%)
- Cushing’s disease—caused by a pituitary tumor stimulating an overproduction of cortisol (10%)
causes of hypopituitarism
- brain damage
- pituitary adenomas
i. Non pituitary tumors—craniopharyngioma is the most common tumor affecting the HP axis in children
ii. Infections—meningitis, encephalitis, hypophysitis
iii. Infarction—sheehan syndrome—the pituitary in pregnancy is enlarged and more vulnerable to infarction
iv. Autoimmune disorders
v. Pituitary hypoplasia or aplasia
vi. Genetic causes
vii. Idiopathic causes
posterior pituitary Hs
a. Neuropeptides—ADH and oxytocin
b. Secreting neurons:
i. ADH neurons have cell bodies primarily in the supraoptic nuclei of the hypothalamus
ii. Oxytocin neurons have cell bodies primarily in the paraventricular nuclei of the hypothalamus
iii. Precursor peptides:
1. ADH—preprossophysin
2. Oxytocin—prepro-oxyphysin
triggers of ADH secretion
- dec in BP–>cardiac and aortic baroreceptors–>sensory neuron to hypothalamus
- dec arterial stretch–>atrial stretch Rs–>sensory neuron to hypothalamus
- inc osmolarity–>hypothalamic osmoreceptors–>interneuron to hypothalamus
secretion of ADH is triggered by:
a. Increase plasma osmolarity—most significant stimulatory factor
b. Decrease blood pressure
c. Decrease blood volume
d. Increase angiotensin II
e. Sympathetic stimulation
f. Dehydration
what does ADH cause and thru what Rs?
a. Blood vessels undergo vasoconstriction—increase blood pressure
i. V1 receptors
b. Increase reabsorption of water—increase blood volume
i. V2 receptors
mechanism of release of ADH in renal CD
- ADH comes from blood and binds to the V2 receptors
- Stimulates G protein which will activate adenylate cyclase
- Causes production of cAMP which goes on to activate PKA
- Causes activation of aquaporin 2 channels that allow water to come into the cell and retain water
hyperosmolarity and ADH
- Too little water causes this
a. Hypothalamus detects too little water
b. Pituitary gland releases ADH
c. Kidneys remove less water from the blood, so less water is lost in urineurine is more concentrated - High level of thirst
- High levels of ADH
- Low levels of water in blood
- Low levels of urine
hypoosmolarity and ADH
- Too much water causes this
a. Hypothalamus detects too much water in blood
b. Pituitary gland releases less ADH
c. Kidneys remove more water from blood, so more water is lost in urineurine is more dilute - Low level of thirst
- Low level of ADH
- High levels of water in blood
- High volume of urine
diabetes insipidus
a. Lack of an effect of ADH on the renal CD
b. Causes frequent urination
c. Large volume of urine is diluted
d. Central vs. nephrogenic DI
i. Central—lack of ADHdec plasma ADH
1. Results from:
a. Damage to the pituitary
b. Destruction the hypothalamus
2. Tx: desmopressin—drug that prevents water excretion
ii. Nephrogenic—kidneys unable to respond to ADHinc plasma ADH
1. Causes:
a. Drugs like lithium
b. Chronic disorders—polycystic kidney dz, sickle cell anemia
2. Desmopressin tx does not work
water deprivation test for DI
i. Allow fluids overnight before test and give b-fast with no fluids
ii. Weigh patient
iii. Allow no fluid for 8 hours
1. Every 1-2 hours: weight pt—stop test if weight drops more than 5% initial weigth
2. Pt empties bladder—measure urine volume and Osm
3. Measure plasma Osm—stop test if Osm >300 mOsm
iv. If results suggest DI, allow pt to drink—not more than twice urine volume of period of fluid deprivation—and administer desmopressing
v. Measure urine and plasma Osm, urine V
SIADH
- inappropriate ADH secretion
a. Excessive secretion of ADH
b. Excessive water retention
c. Hypoosmolariy fails to inhibit ADH release
d. Signs and symptoms:
i. If Na above 120 mmol/L, then no signs
ii. If Na below 120 mmol/L, then hyponatremic encephalopathy
1. Anorexia, nausea, vomiting, confusion, lethargy, headache, convulsion
e. Tx:
i. Fluid restriction
ii. IV hypertonic saline
iii. V2 receptor antagonist–>demeclocycline
