Download The Endocrinology of Calcium and Thyroid Control

Ca and Thyroid Regulation
CALCIUM REGULATING HORMONES
13
• Introduction: effects of Ca / PO4 ions; Parathyroid:
anatomy, histology, PTH; Thyroid: anatomy,
histology, Calcitonin; Kidney: Vit D. Overview
of Ca regulation: bone, kidney, and GI tract as
effectors of Ca regulating hormones.
• PTH: structure, receptor, secretion, effect of
Ca / Vit D metabolites / other factors, effects
• Calcitonin: structure, biological actions, effect
on osteoclasts and bone reabsorption
• Vit D: production and metabolism, absorption,
transport and excretion, biological actions
• Diseases: hypoPTH, low Ca tetany, hyperPTH,
kidney stones, rickets, osteoporosis. Case
study (e.g. hypocalciuric hypercalcemia)
Ca and Thyroid Regulation
THYROID AND ITS REGULATION
• Introduction to the thyroid: anatomy, histology,
hierarchy, feed-back regulation, effect of T3-T4
on Na/K ATPase and uncoupling proteins
• Biosynthesis of T3-T4: thyroglobulin, iodide pump,
iodination and coupling reactions, lysosomes
• T3-T4 effects: metabolism, T°C/F control, growth /
development, reproduction, tertiary hypometabolism
(starvation, hibernation)
• mechanism of action: T4 to T3, T3 receptor,
nuclear / mitochondrial sites, increase enzymes, Na/
K ATPase, uncoupling proteins
• Pathology: goitrogens, hypo and hyperthyroidism,
thyroid hormone resistance
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Ca and Thyroid Regulation
Ca Regulating Hormones
PTH and Vit.D
increase blood
Ca
while
Calcitonin
decreases it
Vit. D
absorption
intestine
blood
Ca
PTH
resorption
bone
formation
Calcitonin
reabsorption
PTH
secretion
Calcitonin
filtration
kidney
blood Ca
decrease
bone formation, osteoblast
kidney, Ca filtration
intestine, Ca secretion
calcium receptor
parathyroid gland
PTH
PTH receptor
Gs / AC
Gq / PLC
bone resorption, osteoclast
kidney, Ca reabsorption, Vit. D
intestine, Ca absorption
Calcitonin
receptor
Gs / AC
Calcitonin
thyroid gland
calcium
receptor
blood Ca
increas
e
The Ca sensor is a GPCR and the Ca regulating
hormones are PTH, calcitonin and Vit D
Page 2
Ca Regulating Hormones
PTH
PTH is only made in the parathyroid gland.
PTH activates both AC and PLC
Ca Regulating Hormones
Calcitonin
The mechanism of action elicited by
calcitonin involves AC and cAMP
Page 3
Ca Regulating Hormones
Vit D
Vit.D activation is inhibited in the kidney by PO4 and in the
parathyroid by Ca on PTH
Ca Regulating Hormones
A model for the general control of bone turnover
Page 4
Thyroid and its Regulation
TRH
TSH
TSH secretion is controlled mainly by a negative feedback of T3 - T4
Thyroid and its Regulation
Thyroid hormones (T3 - T4) derived from the amino-acid tyrosine
Page 5
Thyroid and its Regulation
Hypothalamic Hypometabolic Condition
(as seen in starvation and hibernation)
T3-T4 (low)
TSH (low / normal)
TRH mRNA (low)
UC proteins (low)
TRH-induced TSH release (high)
TRH release (low)
SS inhibits TSH release
Insulin (low)
Glucagon (high)
Cortisol (high)
Epinephrine (high)
LH/FSH (low)
Leptin (low)
Cas, NPY, aMSH, arcuate
thermogenesis (low)
energy expenditure (low)
This condition is also known
as Tertiary Hypometabolism
T3 - T4 have multiple physiological effects
Thyroid and its Regulation
Mechanism of Action
TSH hormone
signal can be
increased by rising
cAMP or by
decreasing
phosphodiesterase
TRH is associated with a GCPR linked to PLC; TSH is associated with
GPCR linked to AC; Vit D is associated intracellular receptors (genomic)
Page 6
Thyroid and its Regulation
Characteristic manifestations of hyper and hypothyroidism
Ca and Thyroid Regulation
Page 7
Ca and Thyroid Regulation
structure
function
Which, increase
or decrease?
a)
b)
How do
you know?
c)
Parts to total?
d)
Two feedbacks and
an absolute
requirement?
Ca and Thyroid Regulation
HPT axis
PTH
Hyp
Ca regulation
Bone
Ca
TRH
PTH
Kidney
Pit
Ca
Parathyroid
Calcemia
TSH
VitD
Thy
VitD
Gut
Ca
Thyroid
Ca
T3-T4
Calcitonin
Ca
S
E
Page 8
Next week question
(after the test #1)
Page 9