Hypothalamic Pituitary Axis

Question 1

what are the 3 axes of the endocrine system and what do they regulate the function of?

Answer 1

a. Hypothalamic-pituitary unit regulates the fcn of thyroid, adrenal and gonads
i. HPT axis
ii. HPA axis
iii. HPG axis (male, female)

Question 2

what do the axes control?

Answer 2

i. Growth
ii. Milk production, ejection
iii. Osmoregulation

Question 3

parts of the pituitary gland and the embryological derivatives

Answer 3

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

Question 4

nuclei of the posterior pituitary

Answer 4

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

Question 5

relationship b/w the hypothalamus and anterior lobe of pituitary

Answer 5

a. is both neural and hormonal

Question 6

Hs secreted by the anterior pituitary

Answer 6

1. Thyroid stimulating H (TSH)
2. Follicle stimulating H (FSH)
3. Luteinizing H (LH)
4. Growth H
5. Prolactin
6. Adrenocorticotropic H (ACTH)

Question 7

how is anterior pituitary connected to the hypothalamus and how do Hs move from one to the other?

Answer 7

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

Question 8

Hypothalamic hypophysiotropic neurons are often …

Answer 8

a. secreted in pulsatile manner and are entrained to circadian rhythms

Question 9

primary endocrine disorder

Answer 9

low or high levels of H due to defect in the peripheral endocrine gland (in a target tissue)

Question 10

secondary endocrine disorder

Answer 10

low or high levels of H due to defect in the pituitary gland

Question 11

tertiary endocrine disorder

Answer 11

a. low or high levels of H due to defect in the hypothalamus

Question 12

what kind of Hs are secreted from anterior pituitary?

Answer 12

peptide

Question 13

corticotrophs

Answer 13

secrete ACTH after being stimulated by CRH

Question 14

thyrotroph

Answer 14

secrete TSH after being stimulated by TRH

Question 15

gonadotroph

Answer 15

secrete LH and FSH after being stimulated by GnRH

Question 16

somatotroph

Answer 16

secrete GH after stimulation by GHRH

inhibited by somatostatin

Question 17

lactotroph

Answer 17

secrete prolactin after being stimulated by TRH

inhibited by PIF (dopamine

Question 18

melanocyte stimulating H

Answer 18

i. ACTH family
1. ACTH has melanocyte stimulating H activity
a. Increase in blood levels of MSH containing fragments can cause skin pigmentation

Question 19

Addison’s Disease*

Answer 19

ACTH levels increase, and skin pigmentation is a symptom of this disorder

Question 20

what is a major regulator of the HPA axis?

Answer 20

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

Question 21

HPT axis

Answer 21

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

Question 22

HPG axis

Answer 22

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

Question 23

stimulus and inhibition of GH secretion

Answer 23

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

Question 24

somatomedins

Answer 24

are formed from the target tissues stimulated by GH and these work in the negative feedback loop

Question 25

how is GH secreted?

Answer 25

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

Question 26

direct and indirect effects of GH

Answer 26

1. Direct: effect on target tissues—skeletal muscle, liver, adipose tissue 2. Indirect: mediated by the production of somatomedins in the liver—IGF-1

Question 27

metabolic actions of GH

Answer 27

1. 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 2. Increase protein synthesis and organ growth a. Increase uptake of AAs b. Stimulates synthesis of DNA, RNA, and protein c. Mediated by somatomedins 3. 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

Question 28

GH deficiency*

Answer 28

1. Decrease secretion of GHRH (due to hypothalamic dysfunction) 2. Decrease GH secretion (secondary deficiency) 3. Failure to generate somatomedins 4. GH or somatomedin resistance (deficiency of Rs) GH deficiency in children is treated with human GH replacement

Question 29

GH excess

Answer 29

-acromegaly 1. Mostly due to a GH secreting pituitary adenoma 2. 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

Question 30

regulation of prolactin secretion

Answer 30

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

Question 31

prolactin and breast development

Answer 31

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

Question 32

prolactin and lactogenesis

Answer 32

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

Question 33

prolactin and | suppression of ovulation

Answer 33

1. Inhibits synthesis and secretion of GnRH

Question 34

prolactin deficiency

Answer 34

1. Results in inability to lactate 2. Causes: destruction of the anterior love of the pituitary or selective destruction of the cells that secrete prolactin (lactotrophs)

Question 35

prolactin excess

Answer 35

1. Results in: a. Galactorrhea—excessive milk production b. Infertility—caused by inhibition of GnRH secretion by prolactin 2. 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

Question 36

panhypopituitarism

Answer 36

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

Question 37

pituitary adenomas

Answer 37

1. 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

Question 38

a. H producing pituitary adenomas release an active H in excessive amounts in the bloodstream what usually results?

Answer 38

1. Prolactinoma—(60%), a tumor that overproduces prolactinassociated with hypogonadism and galactorrhea 2. Acromegaly (adults) and gigantism (children)—caused by an excess GH (20%) 3. Cushing’s disease—caused by a pituitary tumor stimulating an overproduction of cortisol (10%)

Question 39

causes of hypopituitarism

Answer 39

- 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

Question 40

posterior pituitary Hs

Answer 40

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

Question 41

triggers of ADH secretion

Answer 41

- 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

Question 42

secretion of ADH is triggered by:

Answer 42

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

Question 43

what does ADH cause and thru what Rs?

Answer 43

a. Blood vessels undergo vasoconstriction—increase blood pressure i. V1 receptors b. Increase reabsorption of water—increase blood volume i. V2 receptors

Question 44

mechanism of release of ADH in renal CD

Answer 44

1. ADH comes from blood and binds to the V2 receptors 2. Stimulates G protein which will activate adenylate cyclase 3. Causes production of cAMP which goes on to activate PKA 4. Causes activation of aquaporin 2 channels that allow water to come into the cell and retain water

Question 45

hyperosmolarity and ADH

Answer 45

1. 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 2. High level of thirst 3. High levels of ADH 4. Low levels of water in blood 5. Low levels of urine

Question 46

hypoosmolarity and ADH

Answer 46

1. 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 2. Low level of thirst 3. Low level of ADH 4. High levels of water in blood 5. High volume of urine

Question 47

diabetes insipidus

Answer 47

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

Question 48

water deprivation test for DI

Answer 48

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

Question 49

SIADH

Answer 49

1. 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