Hormones that Control Appetite

Thyroid Hormone Anorexigenic Neurons Orexigenic neurons

Lipophilic (Class 1) Decrease appetite Increase Appetite

Action Prenatally: Trigger A-MSH Trigger NPY

● Not required for growth
● Required for normal skeletal and CNS development Leptin, Insulin Ghrelin (stimulus for GH)
Increase glucose oxidation and gluconeogenesis PYY3-36
Increase glycogenesis and glycogenolysis ● Released from the colon
● Inhibits orexigenic neurons
Synthesis 1. Iodine Trapping/Concentration
○ Iodide enters the follicular cell
○ Na-K ATPase pump system
i. Inhibitor: Ouabain Leptin
○ Control point for thyroid hormone synthesis
○ Occurs in the salivary glands, gastric mucosa, Lipophobic (Class 2)
placenta and mammary glands
i. Not stimulated by TSH Action Decreases Appetite (Anorexigenic)
ii. No TH formation Stimulates the sympathetic nervous system
○ Perchlorate/Thiocyanate
● Increases the release of norepinephrine
i. Inhibitors of iodide uptake/Trapping
○ Perchlorate, Pertechnetate, Perrhenate Perchlorate, ○ Increased expression of UCP I
Pertechnetate, Perrhenate (Uncoupling Protein) or thermogenin in
2. Oxidation the nucleus
○ TPO ■ Activation of TAG
i. Oxidizes Iodide (I-) to Iodine (I2) hormone-sensitive lipase (HSL)
3. Iodination or Organification of Thyroglobulin Inhibits TH synthesis
○ Stimulated by TSH
○ inhibited by anti-thyroid drugs
○ Iodine is incorporated into the tyrosine ring of Mode of Action JAK-STATE
thyroglobulin ● Activates IRS-2
i. Forms 3-monoiodotyrosine (MIT) ○ Activates PI3K (inhibits food intake)
○ 2 molecules of iodine incorporated into the tyrosine
residue
i. Forms 3,5-diiodotyrosine (DIT)
○ Catalyzed by TPO
4. Coupling
○ 1DIT+1 MIT = T3
○ 2DIT = T4
○ Catalyzed by TPO
○ Inhibitor: Methimazole, PTU
5. Uptake
○ Acinar colloid droplets are phagocytosed and
pinocytosed
6. Deiodination
○ NADPH-dependent thyrodinase forms Tyrosine
and Iodide

Stimulators

Inhibitors Competes for transport: Thiocynate

Release inhibitor: Lithium

Mode of Action 1. T3 enters the cell membrane via MCT8

2. Nuclear Receptors:
○ Thyroid Hormone Receptor ɑ (TRɑ)
i. Bone, GIT, cardiac and skeletal
ii. Produce high TH levels with detectable TSH
○ Thyroid Hormone Receptor β (TRβ)
i. Liver, kidney, part of hypothalamus
3. T3 Receptor Complex binds to Thyroid Response Element
(THRE)

Feedback T3 is a more potent inhibitor than T4

Regulation