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FHB - Endocrine & Reproductive > Lecture 4 (71): Posterior Pituitary and HPL Axis > Flashcards

Lecture 4 (71): Posterior Pituitary and HPL Axis Flashcards

1
Q

Where are AVP and OXY released from?

A

POSTERIOR PITUITARY

  1. magnocellular neuron (hypothalamus)
  2. Neurhypophysial tract
  3. Posterior pituitary
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2
Q

What is the structure of AVP and OXY?

How are they transcribed?

What are their pro hormones composed of?

A

1.Nonapeptides
(9 amino acids)

  1. Transcribed as a preprohormone
  2. Prohormones:
    AVP + neurophysin II,
    OXY + neurophysin I
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3
Q

AVP:

Cell bodies located where? (2)

PVN has two types of cells: magnocellular and parvocellular. Only ______ neurons project to posterior pituitary.

Parvocellular PVN neurons that contain AVP project to _____and are important for regulating mood (anxiety)/stress.

AVP in magnocellular SON and PVN important for _____

Neurophysin is cleaved from the pro hormone when?

A
  1. paraventricular nucleus (PVN) and supraoptic nucleus (SON).
  2. magnocellular
  3. median eminence
  4. maintaining fluid balance.
  5. secretory granules during axonal transport.
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4
Q

What are the 2 main targets of AVP?

What is it MOST sensitive to?

A
  1. Kidney
  2. Vasculature (Mean Arterial BP)
    - CN 9 and 10

OSMOLARITY
When below 285 mosm/mL = no AVP, above threshold  STEEP INCREASE

  • causes increased water reabsorption and vasoconstriction
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5
Q

What type of signaling does AVP use?

A

G protein

V1 = muscle

V2 = kidney

PLC  IP3  calcium  contracts muscle

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6
Q

What do V2 receptors in the kidney do when AVP is stimulated?

A

V2 receptors in the kidney

-phosphorylates aquaporin 2 channels (only in COLLECTING DUCTS OF KIDNEY)
inserts them into the membrane
allows for water reabsorption into the collecting ducts

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7
Q

What symptom is present in all Diabetets types?

What are the 2 main causes?

A

Excessive urine production

1.Decreased AVP release – most common defect
Hypothalamic or pituitary defect “central” due to trauma, cancer, or infectious disease.

  1. Decreased renal responsiveness to AVP

Genetic: X-linked mutation in AVP type-2 receptor – 90% males

Acquired: LITHIUM treatment, hypokalemia (more common)
AVP levels are normal  responding to osmolarity

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8
Q

What is the function of OXYTOCIN? (2)

Is this positive or negative feedback?

What stops it?

A

OXYTOCIN stimulates
1. contraction of uterus 2. milk ejection (nothing to do with milk production though!)

  1. POSTIVE
  2. Birth or when suckling stops
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9
Q

OXYtocin acts similarly to AVP. How?

A
  1. Increase PLC and IP3
  2. MLCK activated by Ca-CaM
  3. Contraction of smooth muscle
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10
Q

How are GHRH and Somatostatin related?

A

stimulate the anterior pituitary SOMATOTROPHS

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11
Q

What are the 3 components of the HPL axis of GHRH and Somatostatin?

A
  1. Arcuate Nucleus
  2. Somatotrope
  3. Liver
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12
Q

What are the 3 targets of GH?

A
  1. Adipose tissue
  2. Liver
  3. Muscle
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13
Q

What is the structure of GHRH?
Where is it produced?

What does it stimulate?

A

44 amino acid peptide

Produced in the arcuate nucleus

Stimulates growth hormone (GH) from the anterior pituitary

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14
Q

What is the structure of Somatostatin?

What is its function?

What does it inhibit?

A

28 or 14 amino acid peptide (made in PVN of hypothalamus)

Inhibitor of GHRH at the level of the hypothalamus

Inhibits GH and TSH in pituitary

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15
Q

What are the 2 types of SS?

Where are they made?

A

SS28 – made by D cells in stomach and duodenum (Furin)

SS14 made in hypothalamus (PVN) and pancreatic delta cells (PC1/PC2).

SS14 and SS28 have identical amino termini

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16
Q

Somatostatin modulates GHRH pulsatility (decreased frequency) in ______.

Somatostatin inhibits GH release in _____.

A
  1. hypothalamus
  2. pituitary

-inhibits the PULSATILE FREQUENCY of GHRH AND the release of GHRH at the Posterior Pituitary
* NEEDS BOTH FUNCTION*
pulasitility important for downstream function
and to inhibit GH release

17
Q

Which of the following have an inverse relationship?

  1. Somatostatin
  2. GH
  3. GHRH
A

Somatostatin & GHRH And GH

18
Q

Somatotrope (Grown hormone) is pulsatile release, mostly when?

A

At night?

19
Q

How does GH affect IGF-1? (insulin like growth factor)?

A

GH stimulates IGF-I production in the liver

20
Q

What is the negative feedback of GH?

IGF-I mimics insulin in ____, but not _____ and adipose due to lack of receptors

A
  1. IGF-1

1. Muscle, liver

21
Q

GH will not sitmulate IGF-1 in the liver in the absence of what?

A

INSULIN

  • if you are starving and blood glucose levels are low, do NOT want to be growing
  • GH maintains lean body mass - increases protein synthesis in muscle!

IGF-I mimics insulin in muscle, but not liver and adipose due to lack of receptors!!!!
they are direct targets of GH and there are no IGF – 1 receptors here

22
Q

IGF-1 peaks when?

A

IGF1 peaks during puberty  similar to growth hormone
defects with GH are associated with defect in IGF-1

  • HIGHEST DURING PUBERTY
23
Q

What are the direct affects of GH?

Indirect?

A
  1. Adipose tissue = increase lipolysis
  2. Liver = increase IGF’s
  3. Muscle
    = DECREASE glucose uptake (more will be in the blood)
    increase protein synthesis

INDIRCT: via IGF-1

  1. Increase cell size and number of kidney, pancreas, intestine, skin bone, DOES NOT DECREASE glucose uptake in the muscle (this is mediated by GH not IGF-1)
24
Q

What 5 things stimulate GH?

4 Inhibit?

A
  1. GHRH
  2. DOpamine
  3. NE/E
  4. Amino acids
  5. THyroid Hormones

INHIBIT GH:

  1. SOmatostatin
  2. IGF-1
  3. GLucose (hyperglycemia)
  4. Free Fatty Acids (obesity)
25
Q

GH:

_______ by stress, exercise, starvation.

______ with aging, high blood glucose, obesity

A
  1. Increased
    - Increased growth during times of stress and starvation: why? TO MAINTAIN LEAN BODY MASS
  2. Decreased
    - HIGH BLOOD GLUCOSE will decrease GH
26
Q

What are 2 examples of GH excess?

A
  1. Gigantism
    - occurs before closing of epiphyseal plate during childhood
    = long bones get very long
  2. Acromegaly:
    - epiphyseal plate closed, but bones get WIDER
    -Changes in facial features – protuding lower jaw, enlarged lips, tongue, and nose.
    Possible increased organ size
    Most often caused by pituitary adenoma (tumor)
27
Q

What are 2 examples of GH deficiency in children?

A

DWARFISM:

  1. Laron Syndrome:
    - genetic defect in GH receptor
    - no production of IGF -1
    - treatment with IGF-1 can prevent dwarfism
  2. African Pygmy
    - partial defect in GH receptor
    - SOME IGF-1 response
    - plasma levels of GH
    NORMAL
    - no pubertal increase in IGF-1!
28
Q

What is an example of ADULT GH deficiency?

Symptoms?

A

Pituitary Tumor/Surgery

  1. Increased fat deposition, muscle wasting
  2. Reduced bone density, risk of fractures
  3. Higher LDL, Tryglicerides
29
Q

Prolactin is what type of cell?

Because it is this cell, it is not part of a ______.

What is it tonically inhibited by?

A

LACTOTROPHE

  1. Endocrine axis
  2. DOPAMINE

-
Prolactin is not bound to serum proteins – half-life = 20 min.

Prolactin is released in response to suckling “stimulus-secretion reflex”

30
Q

What is the stimulus for prolactin release?

What must decrease in order for it to be secreted?

A

Suckling

  • dopamine

will inhibit ovulation and subsequent pregnancy
CONSTANT access by the child
women will strap the babe and let it nurse whenever, prevents the women from becoming pregnant again (PROLACTIN INHIBITS GnRH!!!!)

31
Q

What is prolactin a potent inhibitor of?

A

GnRH

n

32
Q

Prolactin is in the same family as______

Why is this important?

A

GH

-important when discussing specificity in the receptor

  • when excess of GH
    will bind and activate PROLACTIN = will let galactarrhea as a symptom of excess GH

-excess production of GH can also inhibit GNRH since it is similar to PROLACTIN

33
Q

What can prolactin excess cause?

Deficiency?

A

(pituitary adenoma causes this)
1.Hyperprolactinemia
2. Galactorrhea – milk production or discharge from breast
Reproductive dysfunction - prolactin inhibits GnRH release

DEFICIENCY:

Sheehan’s Syndrome
- lactotropes increase at high rate to prep for birth

Occurs as a result of excessive blood loss/shock during childbirth

Partial pituitary destruction

Usually affects other pituitary cell types – loss of axillary and pubic hair

34
Q

Evaluating of Anterior Pituitary Function depends on what?

A

Hormones must be measured in pairs**
Example: ACTH and Cortisol

Hormones must be measured at appropriate time or longitudinally (normal ranges are broad  need to measure a patient over time)

Stimulation/inhibition tests used to assess normal feedback and pituitary function

35
Q

Example:
Insulin-induced hypoglycemia should result in?

Administration of IGF-I should result in?

A
  1. Increased GH levels

2. Decreased GH levels

FHB - Endocrine & Reproductive (17 decks)

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