Endocrine Flashcards
autocrine
hormone binds to receptors on same cell
paracrine
hormone target nearby cells
endocrine
hormone travels far, targeting many cells and organs
pituitary gland
Link between CNS and periphery
- anterior and psoterior lobes secrete diff peptides, and are anatomically and functionally distinct
- 8 hormones
- regulates every cell in the body
hormones
circulate in blood, easy to measure
lipophilic hormones
thyroid and steroid hormones
- free to enter brain
- regulate all CNS functioning
sex steroids
Estradiol, progesterone, testosterone
- many brain regions
- reproductive processes, behaviour, cognition, emotions, feelings
- explains ind and sex-based brain differences
peptide hormones
made of AAs, complex chain or string
- hydrophilic
- ex. oxytocin + vasopressin (9 AAs)
steroid hormones
4 fused carbon rings + single side chain
- specificity determined by side chain
- lipophilic
- circulate bound to binding globulin (thyroxine binding globulin and sex hormone binding globulin)
thyroid hormones
complex of 2 AA residues (tyrosine)
- lipophilic
- circulate bound to TBG
peptide hormone mode of action
peptide interacts w g protein-coupled, membrane-associated receptor
- transduction to secondary messengers in cell, mediating rapid effects
thyroid and steroid hormone mode of action
free hormone in blood diffuses freely across cell membrane
- binds to cognate intracellular receptor (soluble nuclear receptor)
- receptor complex functions as a TF, mediating delayed genomic effects
- steroids sometimes also have cell surface receptors
anterior pituitary
Produces and releases ACTH, TSH, FSH-LH, PRL, GH
posterior pituitary
Releases AVP, ADH, OT
which pituitary cells produce hormones
each hormone in the pituitary is produced by a specific kind of cell
- corticotropes make ACTH
- lactotropes make prolactin
- Each of these cells is regulated by diff nuclei in hypothalamus
capillary endothelium of the CNS
Forms tight, continuous junction (blood-brain-barrier)
- specialized regions can circumvent this barrier
Median eminence
Below the hypothalamus, links to pituitary
- where nerve axons exit brain
- direct and indirect paths for
indirect path
Cell in hypothalamus produces CRH, transports to nerve terminal ending in ME, where CRH enters into portal circulation of the anterior pituitary. Through portal circulation, CRH makes its way to corticotropes, stimulating the synthesis of ACTH.
direct path
Cell in hypothalamus produces AVP, sent along axon through ME, and stored at nerve terminal in posterior pituitary. Released into circulation when neurons are activated.
hypothalamic nuclei
medial preoptic N., Suprachiasmatic N., Ventromedial N., Arcuate N., Supraoptic N., Paraventricular N.
- Nucleus: group of nerve cell bodies in CNS
paraventricular nucleus
bilateral to ventricle 3
- More medial part (parvicellular) goes through indirect pathway (anterior pituitary)
- More lateral part (magnocellular) goes through direct pathway (posterior pituitary)
RNA-RNA hybridization
Method of detecting presence of specific dna or rna sequence in cells or tissues
- Synthesize complementary RNA probe with radio-, fluorescent-, or antigen-labelled bases
anterior lobe developmental origin
oral ectoderm -> rathke’s pouch -> regressing rathke’s stalk -> anterior pituitary
- non-nervous tissue
- pars distalis (indirect)
posterior lobe developmental origin
neural ectoderm -> neurohypophyseal bud -> pituitary stalk develops into median eminence + posterior pituitary
secretory granules
readily-releasable hormone pools within
- line up towards perivascular space for release
- ex. CRH stim corticotrope cells of ant. pit. to exocytose ACTH granules and to synthesize and accumulate more ACTH
- cells with lots of secretory granules are chromophilic
gonadotrope
anterior pituitary, synth and release FSH + LH
- stim by GnRH from hypothalamus
- secretory granules = chromophilic
basophil (stain blue)
somatotrope
anterior pituitary, synth and release GH in response to GHRH from hypothalamus
acidophil (stain pink)
lactotrope
anterior pituitary, synth and release prolactin (PRL)
acidophil (stain pink)
thyrotrope
anterior pituitary, synth and release TSH in response to TRH from hypothalamus
basophil (stain blue)
corticotrope
anterior pituitary, synth and release ACTH in response to CRH from hypothalamus
basophil (stain blue)
folliculostellate
anterior pituitary support cells
- paracrine function
- no granules = chromophobic
histology of anterior pituitary
weak staining
- little/no secretory granules
- could be immature secretory cell
- supportive function
intense staining
- lots of secretory granules
- eosinophils are bases, stain pink when interacting w acid dye
- basophils are acids, stain blue when interacting w basic dye
anterior pituitary nerve supply?
no nerve supply
- hypothalamic neuron terminates in ME
- pituitary portal system brings hormones to xxtropes
posterior pituitary nerve supply?
hypothalamic neurons terminate in post. pit.
herring body
nerve terminal in posterior pituitary
- stores and releases hormones AVP and OT (secretory granules!!)
- look like swellings
pituicyte
neuroglial support cells of the post. pit.
- physical and nutritive support
anterior vs posterior histology
anterior stains more intensely because hormones are synthesized and stored in secretory granules. posterior is mostly nervous tissue, so it looks like the rest of the brain (low staining)
thyroid gland
TRH from PVH, stimulates TSH synth + release from anterior pituitary, stimulates TH release from follicular cells of thyroid gland (Hypothalamic-pituitary-thyroid axis)
Increased Ca2+ blood conc stimulates calcitonin release from parafollicular cells
thyroid follicle
- follicular cells at edge
- respond to TSH from ant. pit.
- synth TH precursor, stored in thyroid colloid (interior of follicle)
follicle cells
Produce TH in thyroid
- cuboidal
- capture iodide (I-)
- makes thyroglobulin (TGB) TH precursor
- microvilli on apical side, facing lumen
- colloid droplets
parafollicular cell
functionally ind from from follicular cells
- respond to incr in blood Ca2+
- synth + secrete calcitonin
- secretory granules
calcitonin
32 AA, linear
- synth + release stim by incr Ca2+ in blood
- inhibits release of Ca2+ from bone (decr circulating Ca2+)
parathyroid gland
4 glands embedded in posterior thyroid
- responds to Ca2+ conc in blood
- ind of thyroid gland
- chief cells (PTH) and oxyphil cells
chief cell
In parathyroid glands, secrete PTH
- dense cytoplasm
- chromophilic
oxyphil cell
in parathyroid glands
- clear cytoplasm
- chromophobic
- could be inactive chief cells
parathyroid hormone (PTH)
released from chief cells in parathyroid glands
- 84 AAs
- low Ca2+ levels stimulate its synthesis and release
- enhances:
- Ca2+ release from bone,
- Ca2+ absorption in intestine
- Ca2+ reabsorption in kidney
thereby incr Ca2+ levels
calcium homeostasis
calcitonin (parafollicular, thyroid gland) decr Ca2+
PTH (chief cells, parathyroid gland) incr Ca2+
thyroid and adrenal endocrine systems (commonalities)
- catabolic in nature: thyroid hormone incr cellular activity, cortisol mobilizes glucose
- feed-forward elements
- negative-feedback regulation
- PVN releases TRH (thyroid) and CRH (adrenal)
thyroid system
PVN prod TRH -> ant. pit. thyrotropes prod TSH -> thyroid follicular cells prod T3 and T4
adrenal system
PVN prod CRH -> ant. pit. corticotropes prod ACTH -> adrenal prod cortisol
TH synthesis
thyroid follicular epithelial cells
1. Iodide capture
2. thyroglobulin production
3. thyroid peroxidase activity
4. thyroglobulin endocytosis
- iodide capture
(dietary) I- from bloodstream is actively transported into cell, then diffuses across apical membrane into colloid lumen
- thyroglobulin production
cells produce thyroglobulin (main component: tyrosine residues)
active transport into colloid lumen
- thyroid peroxidase
in colloid lumen:
1. oxidizes I- -> I2
2. organification/attachment of iodine molecules to TGB -> mono- or di-iodinated thyronines.
3. coupling of thyronines to create hormone precursors w/ 3 or 4 iodines
- thyroglobulin endocytosis
TSH stimulates endocytosis of TGB.
Vesicle fuses with lysosome.
TGB degraded, leaving T3 and T4.
T3 and T4 secreted into circulation (basal membrane).
iodine atoms of uncoupled tyrosine residues kept and transported back to colloid lumen for future TGB.
thyroid hormone mode of action
Lipophilic: circulate either freely or bound to TBG -> diffuse across cell membrane -> form complex with intracellular cognate receptor -> diffuse into nucleus, function on DNA.
T3 vs T4
Thyroid release: T4»_space;> T3
Activity/potency: T3»_space;> T4 (800:1)
TBG affinity: T4»_space;> T3
- T4 more protected from degradation
Target cells convert T4->T3 ; T4 is a precursor to T3
thyroid hormone function
- Na/K channel openings
- mitochondrial biogenesis
- heart + respiratory rate
- lipid/carb metabolism
- oxygen consumption
- mitochondrial energy prod
- development, growth, reproduction
thyroid hormone dysfunction
- iodine deficiency stops TH synthesis
- excessive TSH stimulation -> goiter [increased cellular growth (hypertrophy) and proliferation (hyperplasia)]
thyroid axis - negative feedback regulation
elevated T3 and T4 signal to PVN to stop secreting TRH, less TSH from thyrotropes in ant pit
Deficient iodine: less T3 and T4, PVN produces lots of TRH. lots of TSH released from ant pit thyrotropes -> goiter
normal thyroid histology
inactive thyroid:
- follicular cells squamous
- wide colloid space (TGB storage)
active thyroid:
- follicular cells cuboidal
- smaller colloid space (TSH stimulated TGB endocytosis)
graves’ disease + histology
immune system generates TSH-like Ig, increases TGB turnover even further
- incr density and packing of follicular cells: tall columnar
- small colloids
- goiter
adrenal axis - negative feedback regulation
elevated cortisol signals to PVN to stop secreting CRH
less cortisol -> PVN prod more CRH -> ant pit (corticotropes) prod more ACTH -> adrenal prod more cortisol
adrenal gland
above both kidneys, cortex and medulla regions
adrenal cortex
Prod steroids
- pituitary-regulated
- neuroendocrine
adrenal medulla
Prod catecholamine (adrenaline + noradrenaline)
- CNS-regulated
- sympathetic
- innervated by pre-ganglionic sympathetic 1st order neurons (come from spinal cord)
cortical zones of adrenal
zona glomerulosa (outer)
zona fasciculata
zona reticularis (inner)
z. glomerulosa
prod mineralocorticoids
z. fasciculata
prod glucocorticoids
z. reticularis
prod androgens
mineralocorticoid
ex. aldosterone (steroid)
- promotes salt retention
glocucorticoid
ex. cortisol (steroid)
- mobilizes glucose
androgen
ex. dehydroepiandrosterone (steroid)
- anabolic - helps produce sex hormones
adrenal steroid biosynthesis
cholesterol from plasma membrane converted to pregnenolone
pregnenolone converted to:
- aldo (z. gl., ACTH + angiotensin II regulated)
- cort (z. f., ACTH regulated)
- DHEA (z. r. ACTH-regulated
adrenal cell histology - adrenocortical
steroid prod + storage
- lipid droplets
- lots of mitochondria (enzyme factory)
adrenal cell histology - adrenomedullary
catecholamine producing
- secretory granules
