PARATHYROID HORMONE

4

• anatomy

• _ glands, adjacent to the thyroid gland

40

• anatomy

• _ mg each

superior

• anatomy

• 2 _: near posterior aspect of thyroid capsule

inferior

• anatomy

• 2 _: near inferior thyroid margin

12-15

• anatomy

• _% of normal persons: 5th parathyroid gland

3rd and 4th

• embryology

• from _ branchial pouches

caudal

• embryology

• 3rd inferior → migrate

thymus

• embryology

• one of them sometimes follows the _ into the superior mediastinum

epithelial

• histology

• _ cells

stromal

• histology

• _ fat

chief cell

• histology

• clear cytoplasm

oxyphil cell

• histology

• larger, eosinophilic granular cytoplasm

PTH

both chief cells and oxyphil cells contain _

Ca2+

• parathyroid hormone secretion

• tight control by _

sigmoidal

• parathyroid hormone secretion

• feedback: steeply _

normal range

• parathyroid hormone secretion

• steep: _ of serum calcium

extracellular calcium-sensing receptor

• parathyroid hormone secretion

• parathyroid cells rely on _

G-protein-coupled

• CaSR

• _ receptor

familial benign hypocalciuric hypercalcemia

• CaSR

• mutation: _ (FBHH)

PT gland and kidneys

• CaSR

• disorder of calcium-sensing by _

brain

• CaSR

• widely distributed in the _

skin

• CaSR

• widely distributed in the _

growth plate

• CaSR

• widely distributed in the _

intestines

• CaSR

• widely distributed in the _

stomach

• CaSR

• widely distributed in the _

C cells

• CaSR

• widely distributed in the _

calcitonin

• CaSR

• regulates responses to calcium in thyroid C cells: _ in response to high EC Ca2+

distal nephron

• CaSR

• _: regulates calcium excretion

extracellular calcium

• parathyroid hormone secretion

• increase in _ → inhibits secretion of PTH

cAMP generation

• parathyroid hormone secretion

• CaSR

• couple to the inhibition of _

PT cells

• parathyroid hormone secretion

• CaSR

• plays a role in setting the response of _ to ambient calcium levels

Mg

• parathyroid hormone secretion

• PT cells: use _ instead of Ca in stimulus-secretion coupling

reversible hypoparathyroidism

• parathyroid hormone secretion

• depletion of Mg stores → _ due to paralysis of PTH secretion

mRNA

• parathyroid hormone secretion

• also regulates synthesis of PTH at _ levels

hypermagnesemia

• parathyroid hormone secretion

• regulator

• _ → inhibits PTH

hypocalcemia

• parathyroid hormone secretion

• regulator

• MgSO4 treatment in pregnancy → _

hypomagnesemia

• parathyroid hormone secretion

• regulator

• _ → stimulate PTH secretion

paralyze release

• parathyroid hormone secretion

• regulator

• prolonged depletion: _

preeclampsia

condition which arises due to hypomagnesemia

B-adrenergic receptors

• parathyroid hormone secretion

• regulator

• stimulate PTH

cAMP

• parathyroid hormone secretion

• regulator

• stimulate PTH

pheochromocytoma

• parathyroid hormone secretion

• regulator

• PTHrP release by patients with _

high levels of Vitamin D

• parathyroid hormone secretion

• regulator

• _ → inhibit PTH gene transcription

Vitamin D analogs

• parathyroid hormone secretion

• regulator

• treat secondary hyperparathyroidism in dialysis patients with renal osteodystrophy

peptide

• parathyroid hormone synthesis

• amino acid _

11

• parathyroid hormone synthesis

• chromosome _

preproPTH

• parathyroid hormone synthesis

• gene encodes for _: with extension added at the amino-end of the mature PTH

23

• parathyroid hormone synthesis

• _ AA signal sequence

endoplasmic reticulum

• parathyroid hormone synthesis

• allow recognition by a signal recognition particle → guide to _

proPTH

• parathyroid hormone synthesis

• endoplasmic reticulum: preproPTH → _

6

• parathyroid hormone synthesis

• _ AA prohormone sequence

furin

• parathyroid hormone synthesis

• golgi: proPTH → PTH by enzyme _

granules

• parathyroid hormone synthesis

• mature PTH: packaged into _

2-4

• parathyroid hormone metabolism and clearance

• half life of _ minutes

liver and kidney

• parathyroid hormone metabolism and clearance

• predominantly cleared in the _

33 to 34

• parathyroid hormone metabolism and clearance

• cleaved at _

36 to 37

• parathyroid hormone metabolism and clearance

• cleaved at _

amino

• parathyroid hormone metabolism and clearance

• cleavage

• _ terminal fragment

carboxyl

• parathyroid hormone metabolism and clearance

• cleavage

• _ terminal fragment

renal filtration

• parathyroid hormone metabolism and clearance

• cleavage

• cleared by _

renal failure

• parathyroid hormone metabolism and clearance

• cleavage

• fragments accumulate in _

IRMA

• assays of parathyroid hormone

• immunoradiometric assay

ICMA

• assays of parathyroid hormone

• immunochemiluminescent assay

10-60

• assays of parathyroid hormone

• normal range: _ pg/mL

intact

• assays of parathyroid hormone

• designed to measure _ hormone species

biologically active

• assays of parathyroid hormone

• designed to measure _ hormone species

calcium

• biologic effects of PTH

• central function: regulate _ levels by concerted effects on 3 principal target organs

bone

• biologic effects of PTH

• target organ

intestinal mucosa

• biologic effects of PTH

• indirect effect on Calcium absorption

increased renal production

• intestinal mucosa

• indirect effect on calcium absorption

• _ of intestinally active Vitamin D 1,25(OH)2D

kidney

• intestinal mucosa

• affects tubular reabsorption of Ca, PO4, HCO3

phosphate reabsorption

• biologic effects of PTH

• kidney

• Inhibition of _ in proximal tubule

calcium reabsorption

• biologic effects of PTH

• kidney

• Increases _ in distal tubule

PT gland removal

• biologic effects of PTH

• _ → profound hypocalcemia → tetany → death

osteoclasts

• biologic effects of PTH

• _ reabsorb bone matter and give calcium back to the blood

bone

• biologic effects of PTH

• main repository of calcium

blood calcium decrease

• biologic effects of PTH

• _ -> get from the bone

reduce calcium loss

• biologic effects of PTH

• in the kidney, _ in urine

phosphate

PTH removes _

intestine

PTH enhances absorption of calcium from _

PTHrP

• biologic effects of PTH

• produced by fetal and adult tissues, as well as tumors

chondrocytes

• cartilage cells

• located in the growth plates

ossification

chondrocytes are responsible for _

calcitonin

• amino acid peptide

• antagonist of PTH

calcitonin resecretion

• calcitonin

• normal blood calcium = _

osteoclast-mediated bone resorption

• calcitonin

• principal action: inhibit _

parafollicular cells

• calcitonin

• secreted by _ of the thyroid

neuroendocrine cells

• calcitonin

• parafollicular cells are _

calcium

• calcitonin secretion

• controlled by _

CaSR

• calcitonin secretion

• use the same _ to sense [Ca2+] changes

hypercalcemia

• calcitonin secretion

• increase secretion of CT in response to _

hypocalcemia

• calcitonin secretion

• shut off hormone secretion during _

osteoclast morphology

• calcitonin secretion

• CT → _ changes rapidly

organelle

• calcitonin secretion

• withdrawal of processes and tracts ruffled order

• _ for bone resorption

renal phosphate excretion

• calcitonin secretion

• inhibits reabsorption of phosphate → promoting _

mild natriuresis

• calcitonin secretion in kidneys

• induces _

calcium renal excretion

• calcitonin secretion in kidneys

• increases _

not essential

• calcitonin secretion in kidneys

• effects on the kidney are _ for its acute effect on serum Ca levels

removal of thyroid gland

_ → no perceptible impact on calcium handling or bone metabolism in postnatal life

mineral homeostasis

high CT levels by medullary carcinoma of the thyroid (MCT) —> no apparent effect on _