Thyroid Hormone Flashcards
relationship between TRH, TSH, and TH
TRH released from hypothalamus –> (+) TSH from pituitary gland
then TSH stimulates TH release from thyroid gland
what hormones does the thyroid produce
T3 and T4
both increase the rate of O2 consumption and metabolism adjusted to alteration in heat production, energy need, caloric supply, and environment temperature
components of a thyroid hormone
2 tyrosines and an iodine
called iodothyronines
reverse T3
unknown function
differs from T3 by only location of 1 of 3 iodines
the alternative product of prohormone T4 and made when less TH action is needed
uptake and concentration of iodide with the gland
1st step
actively transported into the thyroid by Na+/I-cotransporter
‘iodide trap’ which maintains a high ratio of free iodide concentration in the gland to the iodide concentration in plasma
iodide deficiency –> TH deficiency regardless if trap mechanism is functional
iodination of tyrosine within thyroglobulin
inside the follicle lumen, iodide incorporated into tyrosine molecules at specific sites
enzyme = thyroid peroxidase
results = MIT and DIT
coupling of two iodinated tyrosine
thyroid peroxidase
DIT + DIT –> T4
DIT + MIT –> T3
ratio of T4:T3
10:1
restricted iodide availability –> increase T3 formation
how are iodinated thyroglobulins stored
within the follicle as colloid
secretion steps of thyroglobulin
- transferred from the lumen of the follicle –> endocrine cells by endocytosis
- lysosomal enzymes release T3 and T4 from thyroglobulin
- T3 and T4 leave through basement membrane and enter capillary circulation
- MIT and DIT are rapidly de-iondinated by deiodinase and iodide is reused for new hormone synthesis
what thyroid reactions occur in the cell?
interface between cell membrane and the EC colloid space?
in cell = iodide trap, and thyroglobin synthesis
iodination reaction and coupling reaction
T4 is prohormone for what
T3
T4 can also produce some intrinsic IC action of its own
thyroxin-binding globulin
what T4 and T3 circulate bound to (20%)
rest to transthyretin and albumin
create circulating reservoir of T4
which TH is more hormonally active
T3
T4 only 25% as active
thus important to convert T4 –> T3
5-monodeiodinase
reaction T4–>T3
major targets for TH
liver, kidnet, and skeletal muscle
how does TH enter cells
energy dependent transport mechanism
most of the T4 is then converted to T3
both are transported to the nucleus and bind to nuclear receptors
- T3 has higher affinity
interact with DNA to effect transcription
Effects of T3 after it increases transcription in target cells (i.e. intracellular effects)
increases in the following
- sympathetic effect
- expression Na+/K+ ATPase
- number of mitochondria
- respiratory enzymes
- other enzymes, proteins
** all of these together lead to increase in O2 consumption and metabolic rate
Whole body effects of T3
- increase CO and ventilation –> increase O2 –> increase O2 consumption –> increase metabolic rate –> …. A & B
- increase food intake and mobilization of endogenous carbs, proteins, and fat –>… A & B
A. increase CO2, ventilation, urea, renal function, thermogenesis, and sweating
B. decrease muscle mass and adipose tissue
increased TH production effect on basal metabolic rate (BMR)
increases –> increased thermogenesis
effects of this increased heat production on raising body temperature is counteracting by…
- increases in blood flow, sweating, and ventilation –> which cool the body temperature
increasing TH production on the O2 consumption
increases it without increased work
hypothyroid rate = 150mL/min
euthyroid = 250
hyper = 400
increasing TH on Na+/K+ ATPase
increases ADP –> leads to increase in mitochondria O2 uptake
also
increases ADP into mitochondria and ATP out by binding to a receptor on mitochondria
= ‘non-genomic effect’ (does not involve gene transcription)
increasing TH = catabolic or anabolic?
catabolic
leads to more…rapid drug metabolism, vitamin turnover, and steroid hormone metabolism
TH on kidney and kidney function
increases kidney size
and…
renal blood flow, GFR, and increased transport of kidney tubules
–> i.e. increases capacity to reabsorb solutions such as glucose and amino acds
TH on heart and cardiac function
increases cardiac stroke volume
increases heart rate, systolic blood pressure, and decreased diastolic blood pressure
increased sarcolemal uptake of Ca2+ –> shortens diastole… which increases the rate at which heart can beat