Endocrine 3: hypothalamus pituitary Flashcards
Define RAS.
Reticular Activating System
- regulates sleep/wake cycle
Define the hypothalamus-pituitary axis.
- parvocellular neurons converge at the median eminence => hypothalamic releasing hormones travel to the anterior pituitary through the portal vein => affect anterior pituitary cell types => anterior pituitary hormone released into systemic circulation
- magnocellular neurons extend from the hypothalamus to the posterior pituitary => post pit cells release pituitary hormone into systemic circulation
Define PVN.
ParaVentricular Nucleus
- thyroid hormones
- mood, thirst, blood pressure
Define POA.
PreOptic nucleus
- most of the GnRH neurons located here
- reproduction, body temp.
Define SCN.
SupraChiasmatic Nucleus
- circadian rhythms
- involved in melatonin
-
Define ARC.
ARCuate Nucleus
- dopamine
- feeding, mood
Define SON.
SupraOptic Nucleus
- blood pressure and plasma osmolarity
Define ME.
Median Eminence
- floor of the hypothalamus
- where axons of hypothalamic releasing hormone neurons converge and release hormone here into hypophysial portal system
GnRH
- nuclei
- pituitary target
- function
- scattered; mainly POA
- gonadotropes, pituitary releases FSH/LH
- reproduction
CRH
- nuclei
- pituitary target
- function
- PVN
- corticotrope, pituitary releases ACTH
- peripheral release of glucocorticoids
TRH
- nuclei
- pituitary target
- function
- PVN
- thyrotrope, pituitary releases TSH
- thyroid gland release thyroid hormones
GHRH
- nuclei
- pituitary target
- function
- ARC
- somatotrope, pituitary releases GH
- growth and hormone
Somatostatin
- nuclei
- pituitary target
- function
(GHRH inhibitor)
- PeriVN
- somatotrope
- inhibits GH
Dopamine
- nuclei
- pituitary target
- function
the only hypothalamic releasing hormone that is not a peptide (amine)
- ARC
- lactotrope, pituitary releases prolactin
- milk production
What does the size of hypothalamic releasing hormones indicate?
short half-life
Which HRHs use IP3/DAG/PKC? Which HRHs use cAMP?
IP3/DAG
- TRH
- GnRH
cAMP
- CRH
- GHRH
- GHIH/somatostatin
Describe the location of GnRH neurons.
- scattered throughout brain; mostly in POA
- about 1500, but not all are needed
- evolutionary reason = damage to one side of brain will still allow GnRH to function => reproduction
Describe the conservation of GnRH.
- very ancient decapeptide (10 AA)
- only 4 AA vary between species
Describe the structure of GnRH.
PrePro = signal + GnRH + GAP Pro = GnRH + GAP (GnRH Associated Peptide) hormone = GnRH => anterior pituitary
What is Kallman’s Syndrome?
- prevalence: mostly in men b/c Kal1 is X-linked gene; if seen in women, due to Kal2 autosomal
- during development, GnRH neurons fail to move from the nose, unable to cross through the cribiform plate => no GnRH neurons in the brain => no reproduction (sterile)
- defect in olfactory neurons as well => anosmia (can’t smell)
- symptoms = infertility and anosmia
What is the hypophysial portal system?
- vascular connection between hypothalamus and pituitary
- superior hypophyseal artery supplies the pituitary gland
- HRH neurons release hormone at the hypophysial portal vein => secondary capillary plexus
How was the hypophysial portal system discovered?
George Harris - father of neuroendocrinology
- transplanted pituitary gland to kidney…didn’t work => must remain near hypothalamus
- cut off vascular connection between hypothalamus and pituitary…didn’t work => must be connected to hypothalamus
What is the importance of hypothalamic and pituitary hormone pulsatility?
- pulses in GnRH coordinate to pulses in FSH/LH from pituitary
- protects from desensitization and downregulation of receptors
- for GnRH, determines with pituitary hormone (FSH/LH) is released
Describe the structure of FSH and LH.
- constant alpha-glycoprotein subunit, different beta units
- FSH-B unit + alpha = FSH
- LH-B unit + alpha = LH
Describe the mechanism of FSH/LH release from the pituitary.
- GnRH => ME => portal system => anterior pituitary gonadotrophs => GPCR
- DAG/PKC => synthesis of beta subunit (depending on pulse frequency)
- IP3/Ca2+ => release of FSH or LH
What determines if FSH or LH is released from the pituitary?
- fast GnRH pulsatility = LH
- slow GnRH pulsatility = FSH
Define tuberoinfundibular system.
anterior pituitary connection
- hypothalamus => ME => portal system => ant. pit.
Define neurohypophysial system.
posterior pituitary connection
- hypothalamus => post. pit. => circulation
- NO portal system
Describe the structure and composition of the anterior pituitary.
AKA adenohypophysis
- glandular, mostly epithelial cells
- supplied by the superior hypophysial artery
Parts
- pars distalis (90%)
- pars tuberalis
- pars intermedia
Describe the structure and composition of the posterior pituitary.
AKA neurohypophysis
- neural tissue, mostly magnocellular terminal axon and glial cells (pituicytes)
- supplied by the inferior hypophysial artery
Parts
- pars nervosa
- infundibulum (stalk)
What hormones does the posterior pituitary release?
- oxytocin
- arginine vasopressin (AVP = ADH)
Define pituicytes.
- glial-like cells
- provide nutrients and support to posterior pituitary tissue
Define Herring Bodies.
- at the terminal end of magnocellular axons, they are unmyelinated
- this area contains vesicles of AVP/OXY and their copeptide (neurophysin)
What is the copeptide for posterior pituitary hormones?
neurophysin
- AVP/OXY
What is unique about the ME?
- connects the adenohypophysis tract
- lies outside the BBB, so it allows peripheral input to HRHs
What are the main cell types in the adenohypophysis?
Acidophils (most) - somatotrophs, lactotrophs
Basophils - corticotrophs, gonadotrophs, thyrotrophs
Chromophobs - no hormones released; act as support for tissue
How do adenohypophysis cells look on a histological slide?
dark = basophils
pink/orange = acidophils
light pink = chromophobes
Define somatotrophs.
release GH and somatostatin
Define lactotrophs.
release prolactin
Define gonadotrophs.
release FSH/LH
Define thyrotrophs.
release TSH
Define corticotrophs.
release ACTH
Describe the location of trophic cells in the anterior pituitary.
center = corticotrophs = ACTH sides = somatotrophs and lactotrophs (acidophils) = GH/PRL top = thyrotrophs = TSH scattered = gonadotrophs = FSH/LH
Describe the circadian rhythms of GH and ACTH.
GH = peak overnight; hence, sleep is crucial ACTH = gradually increases overnight and peaks in morning (wake up signal)