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38 Cards in this Set

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  • Back
When is Melatonin made
Melatonin

high at night
low at light

marked circadian syntheseis and secretion pattern driven by NE
Melatonin

Synthesis from Tryptophan to Serotonin to Melatonin
Tryptophan catalyzed by Tryptophan hydroxylas
catalyzed by aromatic aa decarboxylase
to serotonin
N-acetyltransferase activated by phosphorylation due to night time release of synaptic NE and beta receptor activation
2nd enzyme HIOMT is induced or activaed activity not circadian

Nacetyltransferase has hightest activity at night
Serotonin is converted at night to melatonin
a
May have membrane (rapid) and nuclear (slower) receptor mechanism

high affiningty GPCRs linked to cAMP

Physiological role is in sleep regulation ..promotes sleep

regulation of repro .. inhibits gonadotropin secretion... pineal distruction may cause premature puberty
Describe Thyroid Autoregulation
Thyroid Autoregulation occurs through plasma iodide ion concentrations at follicular plasma membrane

Increases in iodide intake decrease gland transport and hormone synthesis, and vice versa.

At high plasma iodide concentrations, gland iodide trapping drops precipitously (very high iodide dowes are used to shut down thyroid hormone prod in hyperthroid patients)
Wolff-Chaikoff effect
an effective means of rejecting excessively large quantities of iodide and preventing the thyrid from synthesizing large quantities of thyroid hormones

so if a person has hyperthyroidism giving high iodide will shut down the thyroid
Tell me about TRH
where
how much
how is it regulated
TRH
tripeptide
from prohormone in arcuate nucleus and median eminence
short half life (<5min)
low circulating levels

Hypothalamic TRH released into portal venous sys when plasma T4/T3 levels fall or suppressed when levels rise
What is the fx of TRH
TRH acts on its G protein-linked receptors on thyrotroph cell to stimulate TSH synthesis and release

secretion pulsatile and higher at night

Suppression of TSH by T4/T3 in pituitary is major site of negative FB loop
TSH
dimeric glycoprotein synthesized by pituitary thyrotroph cells
alpha subunit identical to FSH, LH and hCG
Beta subunit confers TSH biological activity

increases growth: DNA, RNA, Protein, Phospholipid, cell size, cell #, follicular formation.. chronic growth = goiter

Increases sythesis of hormone by trapping I, endocytosis of colloid, proteolysis of thyroglobin, increased glucose oxidation and NADPH generation.
What causes Graves' disease
Graves' dx (common hyperthyroid condition) is characterized by receptor antibodies that mimic TSH, hyperstimulating thyroid hormone production and growth of the thyroid gland (diffuse symmetrical hyperthyroid goiter)
What are the underlying causes of goiters?
see Vander
What happens if iodide trapping is absent
decreased thyroid uptake and salivary/blood ratio of radioactive iodide
What happens if peroxidase is absent?
increased early uptake of radioactive iodide, rapid discharge of perchlorate
Deiodinase
Increased uptake of radioactive iodide

excretion of mono and di iodotyrosines
Coupling (organificiation)
a
What is the difference between steroid hormone receptors and thyroid hormone receptors?
steroid hormones homodimerize
thyroid receptors bind to retinoic acid receptors
Vit A isomerizes .. these become ligands for a nuclear receptor

RXR dimerizes with thyroid hormone receptor forming a heterodimeric pair.
Explain why albumin levels are important when assessing Ca2+ status
Low total calcium in patient with no clinical sign of hypocalcemia and albumin is also low so free calcium is in normal range so no symptoms of hypocalcemia. Free calcium is the only active type of calcium
Explain the physiological importance of thyroid hormones in overall development and metabolism
-
Recognize structures of T4, T3 and reverse T3, and understand importance of dietary iodide and its thyroid gland uptake for their adequate biosynthesis.
-
Detail the HPT axis, including negative FB, and explain the role of TRH
-
Understand how TSH stimulates T3 and T4 biosynthesis in the thyroid follicle
-
Describe the role of thyroglobulin and thyroperoxidase in T3/T4 biosynthesis
-
Clarify the importance and role of plasma proteins involved in thyroid hormone transport
-
Be familiar with the similarities and differences between the thyroid hormone receptors and steroid hormone receptors
-
Explain how thyroid hormone receptors act to regulate gene TRXN , including the importance of retinoic acid and its receptors in this process
-
Relate the key effects of thyroid hormone/receptors on the physiology of specific organs
-
Explain the clinical picture of hyperthyroidism and the importance of TSH assays
-
Explain the clinical picture of hypothyroidism, overt and subclinical, and the importance of TSH assays.
-
GH
where does it come from
what does it do
inhibited/stimulated
from anterior pituitary
stimulates growth and metabolism
controlled by GHRH from hypothalamus
somatostatin from pancreas inhibits
excess in childhood = gigantism
excess in adulthood = acromegaly
deficiency in childhood = dwarfism
PRL
where does it come from
what does it do
inhibited/stimulated
from anterior pituitary
stimulates milk production in breasts that have been hormonally prepared during pregnancy
Inhibited by Dopamine
Minor stimulation by PRH from hypothalamus
Causes neg fb to hypothalamus to decreases GnRH
TSH
where does it come from
what does it do
inhibited/stimulated
TSH from ant. pituitary
is a glycoprotein that stimulates thyroid gland to absorb iodine
secretes T3/T4
stimulated by TRH from hypothalamus
inhibitied by T3/T4
ACTH
where does it come from
what does it do
inhibited/stimulated
ACTH from ant. pituitary
stimulates adrenal cortex to release corticoid and sex steroids
stimulated by CRH from hypothalamus
inhibited by negative feedback of glucocorticoids (cortisol)
FSH
where does it come from
what does it do
inhibited/stimulated
FSH from ant. pituitary is stimulated by GnRH from hypothalamus
FSH is inhibited by E or T

FSH in males
stimulates Sertoli cells to carry out spermatogenesis
stimulates seminiferous tubules

FSH in females
stimuates follicle growth
stimulates E secretion
LH
where does it come from
what does it do
inhibited/stimulated
LH in males
stimulates Leydig Cells to secrete T

LH in males
promotes ovulation
stimulates formation of corpus luteum and progesterone secretion
ADH/Vasopressin
where does it come from
what does it do
inhibited/stimulated
presses on blood vessels
causes constriction of arterioles and increase blood pressure
in kidney, stimulates water reabsorption, leading to increase blood pressure
stimulated by increase in plasma OSMOLARITY and decrease in plasma VOLUME sensed by osmoreceptors and baroreceptors.
Aldosterone
where does it come from
what does it do
inhibited/stimulated
produced by cells in the adrenal glomerulosa
stimulates active reabsorption of Na in distal convoluted tubule of kidney nephron -> water is passively reabsorbed
Excess Ald leads to water retention and high bp
Too low Ald leads to dehydration
controlled by renin angiotensis system not ACTH.
Hypoaldosterone is termed Addison's dx
has bodyguard 11β HSD to prevent cortisol acting on aldosterone receptors in kidney to prevent hypertension
Cortisol
where does it come from
what does it do
inhibited/stimulated

Remember the zones of the adrenal gland from outer to inner: Zona Glomerulosa, Zona Fasciculata, Zona Reticularis
cortisol is a glucocorticoid
from the zona fasciculata
is controlled by ACTH
antagonize insulin effects
increase blood glucose levels by:
1) breakdown of proteins into amino acids
2) conversion of amino acids into glucose (gluconeogenesis)
-decrease inflammatory response
-decrease allergic response
Androstenedione
where does it come from
what does it do
inhibited/stimulated
produced by cells in the zona reticularis
controlled by ACTH
can cause masculinization of women due to oversecretion of these adrenal adrogens.
Epinephrine and Norepinephrine
where does it come from
what does it do
inhibited/stimulated
Epinephrine and Norepinephrine
increases blood pressure
increases oxygen consumption
increases heart rate (tachycardia)
increases conversion of glycogen to glucose in blood by liver
vasodilation and dilation of pupils