Hormone Receptors😍

Hormone Receptors

  • Two major types: 
    • Membrane receptors 
    • Intracellular receptors

Classification of Receptors

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Type
Speed of Action
Description
1
Ionotropic Receptors
Fastest acting
↳ (in CNS)
• Receptors on ion channels

Examples
• GABA-A, NMDA, NN, NM, 5HT3
2
Enzymatic Receptors
Slow
• Aka Tyrosine Kinase Receptors
• Cell membrane, intracellular & extracellular ends.
• Drug binds outside, activates intracellular enzyme.

Examples
• Cytokines, Prolactin, Insulin, GH
3
GPCR
Moderate
• Work via cAMP, Ca2+, or ion channels opening.

Examples
• Most other receptors
4
Intracellular Receptors
Slowest acting
• Cytoplasmic or Nuclear.
• Only lipid-soluble drugs.
• Work through DNA (nuclear mechanism).

Examples
• Cytoplasmic:
↳ Vit D, Glucocorticoids, Mineralocorticoids

• Nuclear:
↳ Vit A, Thyroid hormones, Sex hormones.
  • GPCR G-Protein Types:
      • Type
      Mechanism
      Second/Third Messenger
      Gs
      Stimulate adenylate cyclase
      ↑ cAMP → Activate Protein Kinase A
      Gi
      Inhibit adenylate cyclase
      ↓ cAMP
      Gq
      Convert PIP2 to IP3 and DAG
      IP3, DAG → ↑↑ Calcium (intracellular)

Membrane Receptors:

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  • Subgroups:
      1. G-protein coupled receptors (GPCR)
      1. Guanosine cyclase receptors
      1. Tyrosine kinase receptors
      1. Cytokine receptors
      1. Serine kinase receptors
  • Mnemonic: People treated externally by hotel recption
      1. GP doctors → GPCR
      1. Gone vision → Gaunosine
      1. Auto (Autoregulation) Tyre il vannavan → tyrosine
      1. Cycle il varunnavar → cytokine
      1. Siranmar → Serine

Intracellular Receptors:

  • Inside cell (cytoplasm or nucleus).
    • Cytoplasmic:
      • Glucocorticoids
      • Mineralocorticoids
      • Sex steroids
        • Androgen, Estrogen, progesterone
    • Nuclear:
      • Thyroid hormone
      • Vitamin D
      • Retinoic acid (RAR, RXR).
      • It acts via transcription factor
  • Mechanism (intracellular):
    • Lipophilic hormones
    • Penetrate cell membrane → bind cytoplasmic/nuclear receptors.
  • Mnemonic:
    • Internally but superficially
      • Gymmans → Steroids
      • Sex seekers → Sex hormones
    • Internally and deeply
      • Beautiful girls → using Vit D, A and thyroid

GPCRs:

  • Hormone binds GPCR
    • G-protein (alpha, beta, gamma subunits) activated.
    • Alpha subunit separates
      • Activates effector molecule
        • Adenylyl cyclase or phospholipase C
      G-Protein
      Gs (stimulatory) /
      Gi/G0 (inhibitory)
      Gq
      Feature
      Adenylyl Cyclase (AC) Pathway
      Phospholipase C (PLC) Pathway
      Receptors
      Gs → β1, β2

      Gi/G0 → M2, D2, 5HT1
      α1, M1, M3
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      Gs
      (+Adenylyl Cyclase) → ↑cAMP → Protein Kinase A → ↑ Potassium

      •       Cardiac and skeletal muscle → contraction
      •       Smooth muscle → Relaxation

      Gi/G0
      (⛔Adenylyl Cyclase) → ↓cAMP → ↓ Potassium → Relaxation
      Gq
      (+Phospholipase C) → ↑ DAG and IP3 → ↑ Ca

      ↑↑ Smooth muscle contraction
      Second Messengers
      cAMP
      DAG and IP3
      Enzyme Activation
      Activates Protein Kinase A (PKA)
      DAG → activates Protein Kinase C (PKC)

      IP3 → releases       calcium
      Mnemonic:
      SI (Gs, Gi) in a CAMP () Full A (PKA) in AC (Adenyl cyclase)
      Police (PLC) que (Gq) in dagger (DAG) um ayi nikkunnath see (PK C) cheythao I peed 3 (IP3) times to release Calcium (Ca)
      Examples
      β1 → Dobutamine

      β2 → Salbutamol, Ritodrine
      Oxytocin, Angiotensin
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Hormones acting via GPCRs:

  • Gs
    • Beta adrenergic
    • CRH, ACTH, TSH, PTH, LH, FSH, MSH, ADH (V2 receptor)
    • Glucagon, Calcitonin
    • Mnemonic:
      • SI (Gs, Gi) in a CAMP () Full A (PKA) in AC (Adenyl cyclase)
      • Stimulate → Beat (Beta adrenergic) cheyth FLAT (FSH, LH, ACTH, TSH) kambi [CMP (CRH, MSH, PTH) aayi 
  • Gi
    • Alpha 2 adrenergic, Ach (M2, 4)
    • Somatostatin
    • Mnemonic: 
      • Inhibition gone → he was too MAD 2 () Stop ()
        • M2, M4 (Acetylcholine receptors)
        • Alpha 2 adrenergic
        • D2
        • Somatostatin, Serotonin
  • Gq pathway (↑DAG, ↑calcium):
    • Alpha 1 adrenergic hormones,
    • Acetylcholine (via M1, M3, M5 receptors).
    • TRH, GnRH, Oxytocin,
    • ADH (via V1 receptor),
    • Mnemonic: "HAVe 1 M&M, and then some GOATs"
      • H (H1 - not in list, but good to know)
      • Alpha-1 adrenergic (Alpha-adrenergic hormones)
      • V1 (ADH receptor) (ADH via V1 receptor)
      • M1, M3, M5 (Acetylcholine receptors) (Acetylcholine via M1, M3, M5)
      • Then add the "GOaT" hormones:
        • GnRH, Oxytocin, A (ignore for this part or think ADH-V1 again), TRH

Guanosine Cyclase Receptors:

  • Membrane receptors with intrinsic guanylate cyclase activity.
    • Produce second messenger → cGMP
    • Hormones:
      • Nitric oxide,
      • Atrial Natriuretic Peptide (ANP)
    • Mnemonic: Eye Gone → No (NO) Heart (ANP)

Tyrosine Kinase Receptors:

  • Membrane receptors with tyrosine kinase domain (intracellular).
    • Autophosphorylation in intracellular domain upon ligand binding.
    • Activation -> triggers intracellular pathways
      • Ras-Raf-MAP kinase
        • Secrete EGF, NGF
      • AKT-MAP kinase
        • Secrete Insulin, IGF
  • CML and GIST act via Tyrosine Kinase → Rx: Imatinib
  • Mnemonic:
    • Auto tyre il vannavan Rough (Ras-Raf) aytt act (AKT) cheyth →
      • He had rough skin (Epidermal GF) and nerves (Nerve GF)
      • Acted like taking insulin () →
    • He was a PIG (Prolactin, Insulin, GH)??
    • He carries a Kit for Just (GIST) Cumming (CML →Bcr Abl Gene mutation)

Cytokine Receptors:

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  • Membrane receptors; intracellular domain has tyrosine kinase-like activity.
    • Autophosphorylation is not seen.
    • Activation -> triggers JAK-STAT pathway.
    • Hormones: Growth Hormone, Prolactin, Leptin
    • Mnemonic: Jak (JAK) palukudich (PRL) Growcheyth (GH) Cycle (Cytokine) odich → Puberty (Leptin) ayi

Serine Kinase Receptors:

  • Membrane receptors with serine kinase domain (intracellular).
    • Activation -> triggers SMAD pathway.
    • Hormones: MIS (Müllerian Inhibitory Substance), Activin.
    • Mnemonic: Sir um Miss um smart & Active anu
  • Mnemonic: People treated externally by hotel recption
      1. GP doctors → GPCR
      1. Gone vision → Gaunosine
      1. Auto (Autoregulation) Tyre il vannavan → tyrosine
      1. Cycle il varunnavar → cytokine
      1. Sir (and Miss) → Serine
  • Mnemonic:
    • Internally but superficially
      • Gymmans → Steroids
      • Sex seekers → Sex hormones
    • Internally and deeply
      • Beautiful girls → using Vit D, A and thyroid
  • Mnemonic: 
    • SI (Gs, Gi) in a CAMP () Full A (PKA) in AC (Adenyl cyclase)
    • Beat (Beta adrenergic) cheyth FLAT (FSH, LH, ACTH, TSH) kambi [CMP (CRH, MSH, PTH) aayi 
    • he was too MAD 2 Stop
      • M2, M4 (Acetylcholine receptors)
      • Alpha 2 adrenergic
      • Somatostatin 
  • Police (PLC) que (Gq) il dagger (DAG) um ayi nikkunnath see (PK C) cheythao I peed 3 (IP3) times to release Calcium (Ca)
    • Mnemonic: "HAVe 1 M&M, and then some GOATs"
      • H (H1 - not in list, but good to know)
      • Alpha-1 adrenergic (Alpha-adrenergic hormones)
      • V1 (ADH receptor) (ADH via V1 receptor)
      • M1, M3, M5 (Acetylcholine receptors) (Acetylcholine via M1, M3, M5)
      • Then add the "GOAT" hormones:
        • GnRH
        • Oxytocin
        • A (ignore for this part or think ADH-V1 again)
        • TRH
  • Tyrosine KINASE:
    • Auto (Autophophorylation) tyre (Tyrosine kinase) il vannavan Rough (Ras-Raf) aytt act (AKT) cheyth → He had rough skin (Epidermal GF) and nerves (Nerve GF) and took insulin (Insulin is)
  • Mnemonic: Jak (JAK) palukudich (PRL) Growcheyth (GH) Cycle (Cytokine) odich
  • Mnemonic: Sir (Serine) um Miss (MIS mullarian inhibiting substance) um Active (Actin) and SMART (SMAD pathway) anu