Hypothalamus and Pituitary

Question 1

The pituitary gland is located right below the optic chiasm in the sella of the brain

Question 2

How is the pituitary gland connected to the hypothalamus?

Answer 2

the infundibulum

Question 3

What is the posterior lobe (neurohypophysis) of the piutitary gland derived from?

Answer 3

neuroectoderm (left)

Right: adenohypophysis (derived from the oral ectoderm (Rathke pouch))

Question 4

Hormones of the posterior lobe?

Answer 4

ADH and oxytocin

Question 5

How is the hypothalmus connected to the posterior pituitary? What are Herring bodies?

Answer 5

The posterior pituitary is actually a collection of nerve axons whose cell bodies are in the supraoptic and paraventricular nuclei of the hypothalamus that terminate near capillaries. Thus ADH and oxyotcin are actually neuropeptides, that is, they are peptides released from (magnocellular) neurons

Herring Bodies: axonal swellings packed with hormonal granules from the hypothalamic nuclei

Pitucytes: supportive glial cells

Question 6

Although both posterior hormones are synthesized in both nuclei of the hypothalamus, ADH is primarily associated with the _____ nuclei and oxyotcin is primarily associated with _______ nuclei.

Answer 6

ADH- supraoptic

Oxytocin- paraventricular

Question 7

Describe the transmission ans secretion of ADH and oxytocin once synthesized.

Answer 7

The hormones are transported down the axons of the hypothalmic-hypophyseal tract in neurosecretory vesicles and stored in bulbous nerve terminals in the posterior pituitary. Once stimulated, the neurosecretory vesicles are exocytosed and the secreted hormones enter nearby fenestrated capillaries originating from the capillary plexus of the infundibular process

NOTE: The capillary plexus of the infundibular process originates from the inferior hypophysial artery (from the internal carotid artery) and empties into the posterior hypophysial veins. (to the internal jugular vein). NOTE: a small portion of the hypophysial veins connect to the anterior pituitary so traces of these hormones may be seen there

Question 8

How are the posterior pituitary hormones transported in blood?

Answer 8

This venous blood enters circulation and Oxytocin is transported in free form along side Neurophysin I and ADH is carried with Neurophysin II (these are peptides so no carriers)

NOTE: The peptide precursor for ADH is prepropressophysin and the precursor for oxytocin is prepro-oxyphysin. In the Golgi, the signal peptides of each of these are cleaved to form prohormones, which are packaged into secretory vesicles to travel down the axon through the hypothalamic-hypophysial tract, during which the neurophysins are cleaved from the prohormones

Question 9

Where does the anterior lobe of the pituitary originate from?

Answer 9

oral ectoderm (Rathke pouch)

Question 10

What are the anterior pituitary hormones?

Answer 10

FSH, LH, ACTH, TSH, Prolactin, and Growth hormone

FLAT PiG

Question 11

The hypothalamus and the anterior pituitary, unlike the posterior lobe, are related both neurally AND in an endocrine fashion. How are they physically connected?

Answer 11

Directly by the hypothalamic-hypophysial portal blood vessels

Question 12

Describe the hypothalamic-hypophysial portal blood vessels

Answer 12

Arterial blood is delivered to the hypothalamus via the superior hypophysial arteries which distribute the blood into a capillary network in the median eminence, called the primary capillary plexus (thus, in this set of capillaries, hormones from the hypothalamus enter). These capillaries converge to form long hypophysial portal vessels, which travel down the infundibulum to the anterior pituitary. In the lobe, another set of capillaries, the secondary capillary plexus arises from the inferior hypophysial artery (this is where the hormones of the anterior pituitary enter) to be drained to the internal jugular vein

NOTE: in contrast to most organs, the anterior pituitary receives primarily venous blood

Question 13

How are hormones from the hypothalamus transported to the anterior pituitary?

Answer 13

Hypothalamic-releasing hormones are synthesized in the cell bodies of hypothalamic neurons in the ventral hypothalamusand travel down the axons of these neurons to themedian eminence of the hypothalamus. Upon stimulation, the hormones are secreted into surrounding hypothalamic tissue and enter the nearly capillary plexus to be delivered to the anterior lobe

Question 14

TSH is secreted by ____.

FSH and LH are secreted by ____.

ACTH is secreted by ____.

GH is secreted by _____.

Prolactin is secreted by _____.

Answer 14

TSH- thyrotrophs (5%)

FSH and LH- gonadotrophs (15%) (co-secretion)

ACTH- corticotrophs (15%)

GH- somatotrophs (20%)

Prolactin- lactotrophs (15%) (higher in females and in pregnancy)

NOTE: These hormones are synthesized in the anterior lobe in the standard preprohormone, prohormone, and maturation process

Question 15

The hormones of the anterior pituitary are organized into ‘families’ based on structural similarities. What are these families?

Answer 15

TSH, FSH, and LH- family I

ACTH- family II (found in the middle of the lobe)

GH and prolactin- family III (acidophils) found in the peripheral of the anterior lobe (Peripheral hormones -especially GH- are more likely to be impacted by injury)

Question 16

How are the posterior pituiatry hormones relased?

Answer 16

An action potential is transmitted from the cell body in the hypothalamus and the secretory vesicle, with the hormone and their respective neurophysin, is exocytosed to a nearby capillary when Ca2+ levels rise

Question 17

What are the main roles of oxytocin?

Answer 17

Produces milk ejection (aka ‘letdown’) from the lactating breast by stimulating contraction of myoepithelial cells lining the milk ducts

Promotes uterine contraction- can be used to induce labor and reduce postpartum bleeding

Question 18

What factors induce secretion of oxytocin from the posterior pituitary?

Answer 18

suckling; the sight, smell, and sound of an infant; orgasm; and dilation of the cervix

Question 19

T or F. Oxytocin primarily utilizes negative feedback mechanisms

Answer 19

F. It is actually one hormone that works commonly via positive feedback

Question 20

Why are women in labor so response to oxytocin but others are not?

Answer 20

receptors are upregulated via estrogen

Question 21

What stimulates ADH release?

Answer 21

small increases in serum osmolarity causes

larger decreases in ECF volume (10+%)

Angio II

Pain and Nausea

Hypoglycemia

Nicotine, Opiates

Question 22

How does ADH work?

Answer 22

1) binds to V2 receptors on the principle cells of the distal tubules of the CD which is coupled to a Gs protein to increase water reabsorption by inserting more aquaporin 2 channels in the luminal membranes.

Thus, urine will be more concentrated

2) Causes smooth muscle contraction by binding the V1 receptor which is coupled to a Gq protein and acts via phospholipase C to cause increased BP

Question 23

Inhibitors to ADH release?

Answer 23

Ethanol

a-adrenergic agonists

Decreased serum osmolarity

ANP

Question 24

Describe how ADH is stimulated to be released via increased osmolarity?

Answer 24

Increases in serum osmolarity is sensed by osmoreceptors in the anterior hypothalamus.

Question 25

Describe how ADH is stimulated to be released by depleted ECF volume

Answer 25

1. For ECF depletion to stimulate ADH release, there must be a 10+% drop, which is sensed by peripheral baroreceptors and is then transmitted via the vagus nerve to the hypothalamus

NOTE: Drops in ECF override osmolarity changes (i.e. if ECF is low and osmolarity is low, ADH will still be secreted)

Question 26

What is central diabetes insipidus?

Answer 26

Failure of the posterior pituitary to secrete ADH, causing serum osmolarity to rise and large volume of dilute urine to be produced

Question 27

What is nephrogenic diabetes insipidus?

Answer 27

Failure of ADH to bind to the V2 receptor of the principle cells in the collecting duct (or a defect in the Gs protein of adenylyl cyclase). This differs from central DI in that serum ADH will still be high even though serum osmolarity will be high and urine will be dilute

Question 28

How is nephrogenic DI treated? Why?

Answer 28

thiazide diuretics work by inhibiting Na+ reabsorption in the easly distal tubule

Question 29

How is SIADH treated?

Answer 29

demeclocycline or water restriction

Question 30

Why would vasopressin be upregulated in heart failure?

Answer 30

circulating blood decreases to activate ADH (and additional renin release causes systemic vasoconstriction which further increasing afterload of the heart)

Question 31

Normal microscopic appearance of anterior lobe hormones

Question 32

Describe the TSH, FSH, and LH family of anterior pituitary hormones

Answer 32

These are all glycoproteins consisting of identical alpha subunits and unique beta subunits (similarly, human chorionic gonadtropin of the placenta shares these features)

Question 33

Describe ACTH family derivation

Answer 33

All derived from pro-opomelanocortin (POMC) which is then manipulated to form ACTH, y- and b-lipotropin/endorphin, or melanocyte-stimulating hormone (MSH)

Question 34

What is the effect of both POMC and ACTH containing some MSH activity?

Answer 34

Conditions that are associated with over-expression of these products (i.e. Addison disease) can produce skin pigmentation

Question 35

Generation of ACTH is inhibited by what?

Answer 35

cortisol

Question 36

Overview of GH production

Answer 36

Produced by somatotrophs when stimulated by GHRH and is important in body growth and metabolism. Secretion starts at childbirth and increases vastly at puberty and then gradually decreases from that point in life until death and is only secreted during Stage III/IV Sleep (much more so in younger people)

NOTE: Insulin like-growth factor I and thyroid hormones can act as inhibitors for release of GH and GHRH

Question 37

Describe Prolactin regulation

Answer 37

Released from the anterior pituitary and is under tonic inhibition by dopamine but when a stimulus is sensed, this inhibition is released due to neural input into the hypothalamus.

Question 38

The release of prolactin is augmented by what?

Answer 38

oxytocin, AVP, and thyroid releasing hormone

Question 39

What happens when the stimulus for prolactin goes away?

Answer 39

prolactin itself provides a negative feedback to produce more dopamine