Eicosanoids in Disease & Pregnancy Endocrinology

BCH 130 β€” Advanced Human Biochemistry Β· Dr. Radi

build Jul 18 Β· 08:24 Β· CC BY-NC-SA 4.0 Β· owned figures (RDKit / matplotlib)
Dr. Radi

By the end of this unit, you can…

  • Review eicosanoid biosynthesis (arachidonate β†’ COX/LOX β†’ prostaglandins, thromboxane, leukotrienes) as the basis for their disease roles.
  • Connect eicosanoids to disease
  • Explain the pharmacology by target
  • Explain the endocrinology of pregnancy (hCG, the placenta as an endocrine organ, insulin resistance of pregnancy) as the backdrop for its disorders.
Dr. Radi

Today's route πŸ—ΊοΈ

  1. Eicosanoids in Disease
  2. Pregnancy Endocrine Disorders
Dr. Radi

1 Β· Eicosanoids in Disease

"You met the eicosanoids in BCH 120 β€” now watch them cause disease. One fatty acid, two enzymes, and suddenly you can explain pain, fever, clots, asthma, and half the drugs in the pharmacy. This is where the biosynthesis pays off."

Dr. Radi

The branch point that runs the pharmacy

Quick refresher, because everything today hangs on it. Phospholipase Aβ‚‚ frees arachidonic acid from the membrane, and then it forks. Down the COX arm come the prostaglandins and thromboxane; down the 5-LOX arm come the leukotrienes. Same starting fatty acid β€” completely different jobs. Memorize this fork and every drug we meet today explains itself.

Dr. Radi

One family, four diseases

Here's why we care. PGEβ‚‚ dilates vessels, sensitizes pain nerves, and resets the hypothalamic thermostat β€” inflammation, pain, and fever. TXAβ‚‚ aggregates platelets β†’ thrombosis. Cysteinyl leukotrienes clamp the airways β†’ asthma. And PGEβ‚‚ holds the fetal ductus arteriosus open. Same chemistry, four very different bedside stories.

Dr. Radi

Every drug is a block β€” name the target

Now the payoff. Anti-eicosanoid drugs just block one step, and the mediator downstream never shows up. Nonselective NSAIDs (ibuprofen) bar both COX-1 and COX-2. Coxibs (celecoxib) hit COX-2 only. Zileuton blocks 5-LOX; montelukast blocks the CysLT₁ receptor in asthma. Know the target, predict the effect.

Dr. Radi

Aspirin's clever, cruel trade-off

Aspirin is different β€” it irreversibly acetylates COX-1. A platelet has no nucleus, so it can't make new enzyme: one low dose silences its TXAβ‚‚ for the platelet's whole life β†’ antithrombotic. The trade-off? Nonselective NSAIDs strip gastric prostaglandins β†’ ulcers; coxibs drop protective PGIβ‚‚ β†’ more cardiovascular events.

Dr. Radi

2 Β· Pregnancy Endocrine Disorders

"Pregnancy grows a brand-new endocrine organ from scratch β€” the placenta β€” and it rewires the mother's metabolism on purpose. Understand that reprogramming and the disorders make perfect sense: gestational diabetes, pre-eclampsia, thyroid trouble, and the hCG-driven tumors."

Dr. Radi

The placenta is an endocrine organ

Think of pregnancy as growing a temporary endocrine gland. hCG is the opening act β€” it rescues the corpus luteum so progesterone keeps flowing, and it's the hormone your pregnancy test detects. Then the placenta takes over, pouring out progesterone, estrogen, and human placental lactogen (hPL). That last one is the troublemaker: it deliberately makes mom insulin-resistant.

Dr. Radi

Gestational diabetes: a stress test she fails

Why make mom insulin-resistant? To shunt glucose to the fetus. hPL, progesterone, and cortisol drive up resistance, and the Ξ²-cells are supposed to answer with more insulin. Gestational diabetes is when the Ξ²-cells can't keep up β†’ hyperglycemia β†’ a big baby. It clears at delivery but flags lifelong type 2 diabetes risk.

Dr. Radi

Pre-eclampsia: an anti-angiogenic storm

Pre-eclampsia is a placental disease, not a blood-pressure disease. A poorly-perfused, ischemic placenta dumps sFlt-1 β€” a soluble decoy VEGF receptor β€” into mom's blood. It sequesters VEGF and PlGF, so the vessels she needs go unmaintained β†’ endothelial dysfunction, hypertension, and proteinuria. That sFlt-1/PlGF ratio climbs before the pressure does β€” a biochemical early warning.

Dr. Radi

When hCG moonlights on the thyroid

Two more, both about hCG. It shares an Ξ±-subunit with TSH, so it weakly stimulates the TSH receptor β€” early pregnancy brings a mild, physiologic ↑ free T4, ↓ TSH. Untreated hypothyroidism threatens the fetal brain. And in gestational trophoblastic disease, abnormal trophoblast makes hCG go wild.

Dr. Radi

Can you…?

  • ☐ review eicosanoid biosynthesis (arachidonate β†’ COX/LOX β†’ prostaglandins, thromboxane, leukotrienes) as the basis for their disease roles.?
  • ☐ connect eicosanoids to disease?
  • ☐ explain the pharmacology by target?
  • ☐ explain the endocrinology of pregnancy (hCG, the placenta as an endocrine organ, insulin resistance of pregnancy) as the backdrop for its disorders.?

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

Dr. Radi