Cell Signaling😍

REM Sleep – Hormonal Effects

• Mnemonic: REM → Story of Remi
• Remi wanted to get periods (LH, FSH) and produce milk (Prolactin)
• She did not want to grow (GH) or build muscles (Cortisol). She did not take thyroid medication (TSH)

• Most potent stimulus for ADH secretion.
• Plasma osmolality > 280 mOsm/L

• MOA
• Acts on collecting duct cells → bind V2 receptors.
• Activate V2 receptor (basolateral) → ↑ cAMP
• ↑↑ cAMP → AQP2-containing vesicles fuse with luminal membrane → water enters cell from tubular lumen

• Water exits to blood via AQP3/AQP4 (basolateral, constitutive, not ADH-regulated).

Diabetes Insipidus

Thyroid gland secretes:

• T4: Primarily (93%)

• T3: Less (7%)
• T3 is the most active form.

Hormone Conversion:

• Most T4 → active T3
• Occurs in: Kidney, liver
• Mediated by: Type 1 Deiodinase.

• Some T4 → inactive Reverse T3 (rT3).

Transport

• T3 and T4 are lipophilic.

• In blood, thyroid hormones are mostly bound to plasma proteins.
• 99% bound to binding proteins.
• 1% Free (Responsible for actions).

• Major binding proteins:
1. Thyroxine binding globulin (TBG)
• Maximum T4
2. Thyroxine-binding pre-albumin (transthyretin)
3. Albumin
• Maximum T3

• Mnemonic:
• T3 → 3 → M →
• MCT
• MIT + DIT
• T4 → 4 → A
• oATP

Effect of Starvation

• Active T3 → ↑↑ BMR.

During starvation

• body conserves energy to ↓↓ BMR.

• T4 levels stable

• T4 → ↑↑ inactive Reverse T3 (rT3).
• T3 levels ↓↓ , rT3 levels ↑↑

Synthesis Mechanism

Raw Materials:

• Tyrosine: From thyroglobulin (Tg).

• Iodine: Present as iodide in diet.

1. Sodium Iodide Symporter (NIS)

• Basolateral end of follicular cells.

• Function: Iodide trapping 
• I from blood → cell
• Type: 2° active transport 
• uses Na+ gradient by Na+/K+ ATPase
• maintain low Na+ inside the cell.

• Other locations: Salivary gland, mammary gland, placenta.

2. Iodide Antiporter/Pendrin

• Location: Thyroid gland, inner ear.

• Transports Cl- into the cell and I- into the lumen

• Mutation
• Pendred syndrome.
• Symptoms: Goiter, Sensorineural hearing loss.
• Mnemonic: Pendrive → if Go (Goitre) → No song (SNHL)

3. Thyroid Peroxidase (TPO)

• Function:
• Oxidizes reduced iodide (I-) → oxidized I2.
• Organification:
• Catalyzes iodination of tyrosine residues on Tg
• form MIT (monoiodotyrosine) & DIT (diiodotyrosine)
• Coupling reactions:
• MIT + DIT → T3
• DIT + DIT → T4
• DIT + MIT → rT3 (inactive)

• Anti-thyroid drugs:
• Inhibit TPO activity.
• Examples: Propylthiouracil, Carbimazole, Methimazole.

4. Storage

• Thyroglobulin + attached MIT, DIT, T3, and T4
• stored in the colloid in lumen.

• reserve for 2-3 months.

5. Release

• Colloid breakdown → T3, T4 → Released into blood.

Types

• Primary:
• Grave's disease (m/c cause).
• Toxic multinodular goiter
• Toxic adenoma
• Iatrogenic

• Secondary:
• TSH secreting pituitary adenoma.

• Tertiary:
• Hypothalamus problem
• high TRH - very rare

Myxoedema coma

• Long-standing, untreated Hypothyroid complication:
• CNS: Altered sensorium, lethargy → stupor → coma
• Hypothermia
• Bradycardia, low cardiac output
• Hypoventilation → CO₂ retention
• Hypotension
• Hyponatremia (SIADH-like effect)
• Hypoglycemia
• Puffy face, macroglossia, non-pitting edema

Treatment

• IV Hydrocortisone
• Steroids given before thyroxine

• Drug of choice: IV Levothyroxine

• Most common precipitating factor: Infection

• Most important initial step: Secure airway, support breathing

• I₂ induced hypothyroidism

• Excess iodide uptake through NIS 

• inhibits organification and synthesis of thyroid hormones

• Use: Pre-operative treatment for hyperthyroidism
• (e.g., Rx with lugols iodine prior to thyroidectomy).

SAME (Syndrome of Apparent Mineralocorticoid Excess)

Aldosterone

• t½: 20 mins.

Site 1: Primarily in Principal Cell (CD)

• Collecting duct

• Aldosterone acts on Mineralocorticoid Receptor (MR)
• MR (Inactive) → Aldosterone binding → Active MR → ↑↑ activity of

Specific Channels	Function
ENaC	↑ Na⁺ reabsorption
ROMK (Renal Outer Medullary K⁺ channel)	↑ K⁺ secretion
Na⁺-K⁺ ATPase (basolateral membrane):	Pumps 3 Na⁺ out and 2 K⁺ into the cell → maintaining gradient.

• Overall: Na⁺ reabsorption & K⁺ secretion.

Site 2: Type A Intercalated Cell (DCT)

• ↑ H⁺ secretion via H⁺-ATPase

• Overall: H⁺ secretion and HCO₃⁻ reabsorption ⇒ Metabolic alkalosis

MR sites:

• Kidneys, colon, hippocampus, salivary glands, sweat glands.

Factors Regulating Aldosterone Synthesis

• Hyperkalemia → Stimulates aldosterone release.

• ACTH → Increases aldosterone transiently.

Intercalated cells

Classification of Drugs

Special Points

• G means glucocorticoid (anti-inflammatory).

• M means mineralocorticoid (Na+ and H2O retaining)