T3: Hypothalamus Pituitary Axis

hypothalamus & ant. pituitary gland = <state name of system> (2)

neuroendocrine & endocrine systems

hypothalamus sends hormones to ant. pituitary gland thru what …

hypothalamic-hypophysial portal vessels

hypothalamic-hypophysial portal vessels

state:

• vessels’ function

• <name of system> & what does it do

• why is this system important (hint: effect on brain)

• benefit of this system

• function: specialised blood vessels that carries hypothalamic releasing & inhibiting hormones directly to ant. pituitary

• portal system = prevents smth from directly going into systemic circulation

  • reason: if hypothalamus had to release large amounts of hormones into systemic circulation to affect pituitary, it would need:

    • more hormone production

    • larger secretory machinery

    • larger blood vessels & transport system

      → all this takes up more space within cranial cavity → space in brain extremely limited → need portal system as SHORTCUT

• benefit of portal system: instead of releasing large amounts of hormones into general circulation & letting them randomly reach ant. pituitary → system allows for target delivery, efficient signalling

memorise

where are the releasing/inhibiting hormones that regulate ant. pituitary secretions produced?

hypothalamus

which hypothalamic hormone inhibits prolactin secretion

dopamine - inhibits prolactin release from lactotrophs

role of CRH (corticotropin-releasing hormone)

produced by hypothalamus → stimulates ant. pituitary gland to release ACTH → acts on adrenal cortex to produce cortisol

which ant. pituitary hormone stimulates growth & acts on liver to release IGF-1

growth hormone - secreted by somatotrophs

which hormone stimulates milk secretion & which cell produces it

prolactin - produced by lactotropes (or mammotropes)

name the 2 gonadotropins

FSH, LH

target organ of TSH

thyroid gland

how is ant. pituitary regulated by their target hormones

negative feedback

hormone resp for stimulating glucocorticoid production

ACTH, released by corticotropes

pituitary cell plasticity

what happens to gonadotroph cells btwn sexually active & sexually inactive state

no. and/or activity of gonadotrophs increase during sexually active stage → increased FSH & LH secretion

how do lactotrophs change from nulliparous state (not pregnant) to lactation (breast-feeding) to weaning (after breast-feeding)

during lactation, lactotrophs proliferate & increase in size → support high prolactin secretion

in weaning stage, lactotrophs remain large even tho lactation has ended

how do somatotrophs change from childhood to puberty

during puberty, number of somatotrophs increase → support elevated GH secretion

plasticity of hypothalamo-pituitary axis meaning

plasticity = modifiability

→ how axis adapts output patterns based on physiological needs (eg. stress, breast-feeding etc.)

relationship btwn hypothalamus & post. pituitary gland

• name the 2 hormones produced from hypothalamus & name the specific nuclei its produced from

1. ADH (vasopressin) → produced from supraoptic nuclei of hypothalamus

2. oxytocin → produced from paraventricular nuclei of hypothalamus

where are vasopressin & oxytocin stored & released

stored in neuronal terminals of the postr. pituitary → released into blood stream upon neuronal excitation

path of ADH & oxytocin from production to release

produced in hypothalmus → travels down axons → stored in neuronal terminals in postr. pituitary → upon neuronal excitation: hormones released into systemic circulation

ADH acts on where (2) & state action at each site

1. nephron in kidney → increases permeability of DCT & CT to H2O → increased H2O reabsorption

2. arterioles throughout body → vasoconstriction

oxytocin acts on where (2) & state action at each site

1. uterus: stimulates uterine contractions

2. mammary glands: stimulates milk ejection during breat-feeding

state the mechanism of ADH release (2 pathways)

pathway 1: fluid loss, hemorrhage, vomitting, diarrhea → increased plasma osmlarity → …….

pathway 2: fluid loss, hemorrhage, vomitting, diarrhea → decreased MABP

pathway 1: fluid loss, hemorrhage, vomitting, diarrhea → increased plasma osmolarity → shrinkage of osmoreceptors → decreased magnocellular neuron inhibition → ADH release increases → increase water reabsorption → fluid balance restored

pathway 2: fluid loss, hemorrhage, vomitting, diarrhea → decreased MABP → decreased baroreceptor stretch & firing → signal sent via 9th & 10th cranial nerve afferents → increased sympathetic tone (sympathetic activity) → decreased magnocellular neuron inhibition → ADH release increases → increase water reabsorption → fluid balance restored

what are magnocellular neurons & where are they located

large neuroendocrine cells in hypothalamus, synthesizes & secretes ADH and oxytocin

explain the ADH action cascade

(start from water deficit)

water deficit → extracellular osmolarity (solute conc.) increases → detected by osmoreceptors → post. pituitary gland secretes ADH → increased plasma ADH → increased H2O permeability in distal tubules & collecting ducts → increase H2O reabsorption → less H2O excreted → negative feedback/ inhibits ADH action cascade (no longer in water deficit)

• what type of feedback loop is the oxytocin release mechanism

• state the oxytocin release mechanisms

  • mech 1: stimuli = nipple stimulation: sucking of lactating breast

• positive feedback loop

• mech:

  1. nipple stimulation: sucking of lactating breast

  2. PVN & SON stimulated

  3. post. pituitary gland releases oxytocin

  4. myoepithelial in mammary glands cells contract

  5. milk ejection

• state the oxytocin release mechanisms

  • mech 2: stimuli = stretch of cervix (late pregnancy/labour)

1. stimuli: stretch of cervix (late pregnancy/labour)

2. PVN/SON in hypothalamus stimulated

3. post. pituitary gland releases oxytocin

4. uterine contraction occurs

name an inhibitor of oxytocin release

fear, pain, noise, fever

what is smth pregnant women shld avoid to prevent risk of premature uterine contraction & delivery + when shld she avoid this

direct nipple manipulation during 3rd trimester

child growth

what hormone is critical for growth & development during infantile & early childhood phase?

thyroid hormones

what hormone is critical for growth during childhood & pubertal phases?

growth hormone

what does growth hormone produce to accelerate linear growth

IGF-1

effect of sex hormones during puberty (2)

cause growth spurt & boost growth hormone secretion

name the 3 main sex hormones

estrogen, progesterone, testosterone

what is another effect of sex hormones, during LATE puberty, apart from growth spurt & increased growth hormone secretion

closing of epiphyseal growth plates & cessation of growth

what is adult height & measured in what unit

proportion of adult that is gained during each period, measured in %

what is the adult height value during

1. fetal

2. infantile (baby)

1. fetal = 30% of adult height

2. infantile = 15% of adult height

what does percentiles of weight & height (at a particular age) indicate

the physical status of a subject compared to statistical averages (50th percentile)

1. state mechanism of growth hormone release

2. what hormone inhibits growth hormones

1. hypothalamus releases GHRH (growth-hormone releasing hormone)

2. GHRH causes somatotrophs to synthesize & release GH

3. somatostatin inhibits GH release by somatotrophs

state another substance that inhibits growth hormone release

IGF-1 (insulin-like growth factor 1)

how does IGF-1 suppress GH release

GH stimulates IGF-1 secretion from peripheral target tissues (eg. liver) → inhibits GH release from somatotrophs, suppress GHRH release from nuclues in hypothalamus, increase somatostatin secretion → GH production decreases & stops

indirect effect of growth hormone

• which organ does it target

• what is secreted

• overview of effect

• state the 2 effects

indirect = growth-promoting effect

→ targets liver & other tissues

→ stimulates IGF-1 secretion from peripheral tissues, causes:

1. skeletal effect → increased cartilage formation & skeletal growth

2. extraskeletal effects → increased protein synthesis, cell growth & proliferation

direct effect of growth hormone

• overview of effect

• state the 2 effects

• overview: metabolic, anti-insulin

• effect:

  1. fat metabolism: increases fat breakdown & release

  2. carbohydrate metabolism: increase blood glucose & other anti-insulin effects

name 4 factors that stimulate GH secretion

• low blood glucose (GH increases blood glucose)

• fasting & starvation

• strenuous exercise

• deep sleep

name 4 factors that inhibit GH secretion

1. high blood glucose

2. aging

3. obesity

4. insulin-like growth factor-1

name the 2 conditions excessive growth hormone secretion cause

1. acromegaly

2. giagantism

1. state clinical features of acromegaly

2. lab tests for acromegaly (glucose suppression test & insulin)

1. clinical features of acromegaly = excessive growth of hands, feet, jaw & internal organs but not height + change in facial structure

2. lab test = impaired glucose suppression test as GH is high, insulin resistance (prone to diabetes)

state the pathogenesis of gigantism

abnormally high IGF-1 → stimulation of cell proliferation & differentitation at epiphyseal growth plates → excessive linear skeletal growth

state other clinical effects of excess growth hormone:

1. cardiovascular:

ventricular hypertrophy (heart thickening), congestive heart failure (blood cannot enter heart → leaks out in lungs → pulmonary edema/congestion)

state other clinical effects of excess growth hormone:

2. metabolic

diabetes mellitus, glucose intolerance

state other clinical effects of excess growth hormone:

3. musculoskeletal

prognathism (prominent jaw, enlarged mandible), frontal bossing

clinical feature of growth hormone deficiency

low bone growth & premature closing of epiphyseal plates → short height, normal weight

treatment of growth hormone deficiency

oral growth hormone therapy

memorise

state 2 effects of prolactin on mammary glands

1. mammary gland development

2. milk production

what inhibits prolactin release

dopamine

why is women not capable of having child during first 6 months of child-bearing

prolactin secreted during breast feeding → inhibits GnRH release → no FSH & LH release → no ovulation & spermatogenesis

what is a prolactin releasing factor

TRH (thyroid releasing hormone)

what condition suppress gonadal function & explain the mech

hypothyroidism

hypothyroidism = low T3/T4 hormone → negative feedback: TRH increases → increased prolactin production → less GnRH released → less FSH & LH → gonadal function suppressed

give 2 examples of suppressed gonadal function

irregular menstrual cycle

fertility problems

approach to prolactinoma

if px. has hyperprolactinemia & prolactin > 200ng/mL, what is diagnosis?

prolactinoma

= benign tumor of pituitary gland that produces excess prolactin

if px. has hyperprolactinemia & prolactin <200ng/mL, what condition is ruled out

hypothyroidism

if px. has hyperprolactinemia & prolactin <200ng/mL, what is diagnosis

px. on drugs known to cause hyperprolactinemia

what is the diagnostic tool used for hyperprolactinemia

MRI of pituitary gland

for diagnosis of hyperprolactinemia, what to rule out first

pregnancy

name 5 conditions to rule out for diagnosis of prolactinoma

1. pregnancy

2. primary hypothyroidism

3. chronic liver & kidney disease

4. estrogen therapy

5. oral contraceptive use

state 2 symptoms of prolactinoma

1. headache

2. visual disturbance

explain how visual disturbance occurs in prolactinoma

• pituitary gland is located below optic chiasm

• prolactinoma = tumor in pituitary gland → tumor grows & compresses optic chiasm → visual loss: bitemporal hemaniopa

what type of visual loss occurs in prolactinoma

bitemporal hemaniopa

what type of medication causes prolactinoma

antipsychotics: medication blocking D2 receptors

what 2 conditions causes reduced prolactin elimination

renal failure & liver insufficiency

state 4 other symptoms of hyperprolactinemia

fertility problems

galactorrhea = milk production in male

sexual dysfunction

osteoporosis