Hypothalamic and Pituitary Relationships Pt. 1 (Creamer) Flashcards
What are the sub-structures a/w the pituitary gland and how is it connected to the hypothalamus?
- pituitary gland (hypophysis)
- anterior pituitary (adenohypophysis): epithelial portion
- posterior pituitary (neurohypophysis): neural portion
- hypophysial stalk: physical connection between hypothalamus and post pit; hormonal connection between hypothalamus and ant pit (sends releasing hormones to ant pit)
What effects would be seen with damage to the hypophysial stalk, and with tumors in the pituitary?
- hypophysial stalk damage: would inhibit releasing hormones to ant pit, leading to loss of function in this area; oxytocin and vasopressin would still go to post pit, thus function may be reduced but still retained
- pituitary tumor: due to anatomical location in close a/w optic nerve, sx may include visual problems and dizziness
How are the hypothalamus and posterior pituitary connected?
- post pit is neural tissue, w/ its cell bodies located in hypothalamus (supraoptic nucleus (SON) and paraventricular nucleus (PVN))
- the hypothalamus produces neuropeptides in these nuclei and, via axons, sends the hormones (vasopressin and oxytocin) to the post pit
How is the hypothalamus connected to the anterior pituitary gland?
- communications between the two are both neural and hormonal
- hypothalamic neurons produce releasing/inhibiting hormones
- the hormones are secreted via the hypothalamic-hypophysial portal blood vessels into the anterior pituitary where they either cause release/inhibition of downstream hormone production in ant pit
Compare and contrast the connections between the hypothalamus and posterior pituitary vs the anterior pituitary:
- posterior pituitary: connections are neural only, hormones are produced in hypothalamus and projected via axons to the posterior pituitary (aka no hormones are actually prod in post pit)
- anterior pituitary: connections are both neural and hormonal, releasing/inhibiting hormones are prod in hypothalamus that are secreted via hypothalamic-hypophysial portal to the anterior pituitary where hormone production is either stim/inhibited
How are the hormones of the anterior pituitary organized?
(via structure and function homology)
- ACTH family:
hypothalamus releases CRF (+) > corticotrophs > ant pit secretes ACTH
- TSH, FSH, LH family:
hypothalamus releases TRH (+) > thyrotrophs > ant pit secretes TSH
hypothalamus releases GnRH (+) > gonadotrophs > ant pit secretes LH and FSH
*hormones in this family all share same alpha subunit, the beta subunit is the part that differs*
- GH and prolactin family:
hypothalamus releases GHRH (+) or somatostatin (GHIH) (-) > somatotrophs > ant pit secretes GH
hypothalamus releases PIF (dopamine) (-) or TRH (elevated) (+) > lactotrophs > ant pit secretes PRL
Define primary, secondary, and tertiary endocrine disorders:
- primary: defect of hormone production/release within peripheral glands
- secondary: defect of hormone production/release within pituitary gland
- tertiary: defect of hormone production/release within hypothalamus
Describe the HPG hormonal axis in terms of the testes:
- hypothalamus releases GnRH in pulsatory waves
- GnRH stimulates anterior pituitary to produce/release LH and FSH
- LH acts on Leydig cells of the testes, causing them to produce testosterone
- testosterone along with FSH act on the Sertoli cells of the tests to produce androgen-binding proteins and activate spermatogenesis
- this is a negative feed back system:
testosterone inhibits ant pit production of LH and hypothalamic production of GnRH
inhibin (prod by Sertoli cells) inhibits ant pit production of FSH
Describe the HPG hormonal axis in a female:
most phases of the menstrual cycle follow negative feedback system:
- hypothalamus releases GnRH in pulsarory waves
- GnRH stimulates anterior pituitary to produce/release LH and FSH
- LH acts on Theca cells of the ovaries, causing them to produce androgens
- androgens along with FSH act on the Granulosa cells of the ovaries to produce progestins and estrogens
- feedback: progestins, estrogens, and inhibin produced by granulosa cells inhibit hypothalamic production of GnRH and ant pit production of LH and FSH
ovulation portion of the menstrual cycle follows a positive feedback system:
- hypothalamus releases GnRH in pulsatory waves
- GnRH stimulates anterior pituitary to produce/release LH and FSH
- LH acts on Theca cells of the ovaries, causing them to produce androgens
- androgens along with FSH act on the Granulosa cells of the ovaries to produce estrogens
- feedback: estrogens produced by the granulosa cells increase production of GnRH in hypothalamus and LH and FSH in the ant pit
- condition caused by excessive exposure to growth hormone by anterior pituitary causes liver to over-produce IGF-1 after closure of growth plates
- can cause insulin-insensitivty in peripheral organs/cells which leads to TIIDM
- sx: enlarged hands, feet, face along w/ a slew of other sx
acromegaly
Describe the growth hormonal axis:
- hypothalamus releases GHRH (+) or somatostatin (GHIH, (-))
- anterior pituitary is activated by GHRH and produces/releases GH (somatotropin)
- GH activates JAK-STAT (tyrosine kinase associated PW) within liver and bones
- direct effects on liver and bones causes cell growth/metabolism
- liver and bones also produce IGF-1 (somatomedin C) which has growth stimulating and repair effects on bone, muscle, and adipose tissues
- IGF-1 is inhibitory on ant pit prod of GH
- IGF-1 is indirectly inhibitory by stimulating on hypothalamic prod of GHIH
- GH is inhibitory on hypothalamic prod of GHRH
How is growth hormone (GH) from anterior pituitary secreted throughout the day?
- GH secretion varies throughout the day: primarily during sleep (sleep disturbances perturb secretion), peaks w/ exercise, also varies with meals
- GH secretion varies throughout lifetime: avg secretion is high during early childhood, peaks at puberty, remains relatively stable throughout adulthood, then starts declining later in life
What lifestyle/physiological factors affect GH secretion?
- fasting/hunger/starvation
- hypoglycemia
- hormones of puberty
- exercise
- sleep
- stress
What are the direct and indirect effects of GH?
- direct: stimulates response in bone/muscle, growth of cells in these tissues due to hypertrophy, increase in cell numbers/hyperplasia, increase in metabolism (glycogen/fat breakdown for increase in energy/protein syn)
- indirect: acts upon liver to produce IGF-1 which causes proliferation/growth of many cells through hypertrophy/hyperplasia and increases metabolic effects in these cells
- excessive production of growth hormone (GH) in anterior pituitary before growth plates close
- sx: excess height and girth of body
gigantism
How would the following growth hormone (GH) deficiencies present:
- GH insensitivity (primary deficiency):
- secondary deficiency:
- tertiary deficiency:
- GH insensitivity (primary deficiency): problem w/ liver insensitivity to GH; increased systemic levels of GH (insensitivity of GH in liver reduces prod of IGF-1 limiting negative feedback on GH in ant pit) and low levels of IGF-1
- secondary deficiency: GH not produced/released from ant pit; causes low IGF-1 levels due to low levels of GH
- tertiary deficiency: GHRH not produced/released from hypothalamus; low levels of GHRH from hypothalamus causes low levels of GH
How does growth promoting factors respond in a fed state w/ adequate protein intake?
- increased carb intake = increased blood sugar = adequate insulin availability
- increased protein intake = adequate amino acid availability
>
liver produces IGF-1
>
IGF-1 stimulates mitogenesis, lipolysis, cell differentation
How do growth factors respond in a fed that w/ low protein intake?
- increased carb intake = increased blood sugar = adequate insulin availability
- decreased protein intake = inadequate AA availability
>
GH is inhibited, liver will not produce IGF-1
>
lack of IGF-1 leads to lipogenesis and carb storage
>
weight gain
How do growth factors respond in a fasted state?
- decreased carb intake = hypoglycemia = inadequate insulin availability
- increased protein intake = adequate AA availability
>
peripheral metabolism shifts to lipids are energy source
>
GH levels increase
liver will produce IGF-1
>
lipolysis, ketogenic metabolism, diabetogenic (insulin insensitivity)
(GH raises blood glucose by decreasing peripheral glucose uptake and stim hepatic gluconeogenesis)
What are the metabolic functions of growth hormone (GH)?
- diabetogenic effect: increase in blood glucose (insulin resistance), decrease glucose uptake/utilization by target tissues, increase lipolysis in adipose tissue, decrease in blood insulin levels
- protein synthesis and organ growth: increase uptake of AA’s, DNA/RNA/protein syn stimulated (mediated by somatomedins (IGF-1))
- increased linear growth: stim syn of DNA/RNA/proteins, increased metabolism in cartilage-forming cells and chondrocyte proliferation
Describe the general prolactin axis:
- hypothalamus secretes dopamine which inhibits prolactin production (tonic inhibition)
- during pregnancy (5th week), body starts secreting prolactin from ant pit lactotrophs in pulsatile form
- prolactin stimulates mammilary gland growth and milk production
- prolactin negatively inhibits GnRH apart of the HPG axis, and can cause lactating amenorrhea
Describe the oxytocin axis of the posterior pituitary:
- begins as production of prepro-oxyphysin in the cell body of hypothalamic neurons
- prepro-oxyphysin is cleaved and packaged into vesicles as pro-oxyphysin
- vesicles travel via the hypothalamic-hypophyseal tract (axons of neurons) where additonal cleavage of neurophysins occur
- reaches posterior pituitary where it has been modified into final form, oxytocin
- oxytocin is stored in vesicles until it is released into circulation w/ main effects being in breast and uterine tissues
What are the 2 main functions of oxytocin?
- milk ejection: milk letdown (stimulates contraction of myoepithelial cells lining milk ducts), major stimulus (suckling, but also sight/sound/smell of infant)
- uterine contraction: stim by dilation of cervix/orgasm, stim uterine contractions, creates positive feedback loop
