Neuroendocrinology

BCH 120 β€” Metabolic & Endocrine Biochemistry Β· Dr. Radi

build Jul 17 Β· 11:10 Β· CC BY-NC-SA 4.0 Β· owned figures (RDKit / matplotlib / PyMOL)
Dr. Radi

By the end of this unit, you can…

  • Distinguish neurohormones from neurotransmitters and classic hormones, and describe the adrenal medulla's chromaffin cells and the catecholamine synthesis pathway (tyrosine β†’ L-DOPA β†’ dopamine β†’ norepinephrine β†’ epinephrine)
  • Explain catecholamine reuptake and degradation (COMT, MAO; MAO inhibitors as antidepressants) and the four adrenergic receptor subtypes (Ξ±1/Ξ±2/Ξ²1/Ξ²2) with their G proteins and effects
  • Describe the pineal gland and how it converts serotonin to melatonin in the dark to set circadian rhythm
Dr. Radi

Today's route πŸ—ΊοΈ

  1. Neurohormones & Catecholamine Synthesis
  2. Clearing Catecholamines & Adrenergic Receptors
  3. The Pineal Gland, Melatonin & Your Clock
Dr. Radi

1 Β· Neurohormones & Catecholamine Synthesis

"Where does the nervous system end and the endocrine system begin? Right here β€” in cells that are half neuron, half gland. The adrenal medulla's chromaffin cells fire on nerve command and squirt adrenaline into the blood. And you need to know how they build it."

Dr. Radi

Neurotransmitter, hormone β€” or both?

First, a definition that ties the two control systems together. A neurotransmitter is released by a neuron across a tiny synapse to the very next cell β€” fast and local. A hormone is released by a gland into the blood to reach distant targets β€” slower, body-wide. A neurohormone is the hybrid: a neuron that dumps its messenger into the bloodstream to act far away. Two organs do exactly this β€” the posterior pituitary (you've met it) and the adrenal medulla (you're about to).

Dr. Radi

The adrenal medulla: a gland run by nerves

The adrenal gland is really two glands stacked together, from two different embryos. The outer cortex comes from mesenchyme and makes steroids (the next several units). The inner medulla comes from neural-crest cells β€” it's basically a modified sympathetic ganglion. Its chromaffin cells are fired by spinal nerves, and when they fire they release catecholamines β€” epinephrine and norepinephrine β€” straight into the blood. Epinephrine is always a neurohormone, never a neurotransmitter.

Dr. Radi

KNOW this pathway: how you build adrenaline

This is a "must-know" sequence, and it's a tidy one β€” start with an amino acid and add one change at a time. Tyrosine β†’ (tyrosine hydroxylase, TH β€” the rate-limiter, adds the second ring-OH β†’ a catechol) β†’ L-DOPA β†’ (AAD, decarboxylase β€” drops the –COOH) β†’ Dopamine β†’ (DBH, adds a Ξ²-OH) β†’ Norepinephrine β†’ (PNMT, adds an N-methyl) β†’ Epinephrine. Four enzymes, four small edits. (Bonus: L-DOPA is the Parkinson's drug β€” it refills brain dopamine.)

Dr. Radi

2 Β· Clearing Catecholamines & Adrenergic Receptors

"A fight-or-flight signal has to end fast β€” so catecholamines are cleared in seconds by reuptake and two enzymes you should know by name. Then the payoff: the SAME two hormones do opposite things depending on which adrenergic receptor they hit."

Dr. Radi

Turning the alarm off: reuptake, COMT, MAO

Adrenaline is meant to be brief, so the body clears it fast three ways. Reuptake: nerve and target cells rapidly pull the catecholamines back in (especially important at synapses). COMT (catechol-O-methyltransferase) methylates them, mainly in the liver. MAO (monoamine oxidase) oxidatively deaminates them. That last enzyme has a famous clinical hook: MAO inhibitors were among the first antidepressants β€” block the breakdown, and catecholamine (and serotonin) tone goes up.

Dr. Radi

Adrenergic receptors: same hormone, four switches

Here's why epinephrine can speed your heart and open your airways at once: there are four adrenergic receptor subtypes, all GPCRs, each wired to a different G protein. α₁ β†’ Gq β†’ IP₃/DAG/Ca²⁺ (vasoconstriction). Ξ±β‚‚ β†’ Gi β†’ ↓cAMP (a presynaptic brake; ↓insulin). β₁ β†’ Gs β†’ ↑cAMP (the heart β€” rate and force). Ξ²β‚‚ β†’ Gs β†’ ↑cAMP (bronchodilation, glycogenolysis). Same ligand, opposite outputs β€” it all depends on the receptor. (That's why a Ξ²-blocker slows the heart while an Ξ±-agonist clears your nose.)

Dr. Radi

3 Β· The Pineal Gland, Melatonin & Your Clock

"One more neuroendocrine organ, and it's the one that keeps time. The pineal gland reads light and dark and turns it into a chemical signal β€” melatonin β€” that sets the rhythm of your whole day."

Dr. Radi

The pineal gland keeps time

The pineal gland is your circadian clock β€” an evolutionary leftover that once sensed light directly and still runs on it (via neural day/night signals). It makes melatonin from serotonin (which the gland builds from the amino acid tryptophan), switched by darkness: in the light, serotonin builds up; when the eye senses dark, the enzyme NAT converts it to melatonin, secreted at night. Melatonin acts on the brain's master clock, the suprachiasmatic nucleus, to set your ~24-hour rhythm and normal sleep. Sleep aids like ramelteon are melatonin-receptor agonists working through this very pathway.

Dr. Radi

Can you…?

  • ☐ distinguish neurohormones from neurotransmitters and classic hormones, and describe the adrenal medulla's chromaffin cells and the catecholamine synthesis pathway (tyrosine β†’ L-DOPA β†’ dopamine β†’ norepinephrine β†’ epinephrine)?
  • ☐ explain catecholamine reuptake and degradation (COMT, MAO; MAO inhibitors as antidepressants) and the four adrenergic receptor subtypes (Ξ±1/Ξ±2/Ξ²1/Ξ²2) with their G proteins and effects?
  • ☐ describe the pineal gland and how it converts serotonin to melatonin in the dark to set circadian rhythm?

If any box stays empty, the practice site has a drill for it. πŸ§ͺ

Dr. Radi