Endocrinology | Receptor Pathways

Endocrine Receptor Pathways

The lecture explains how hormones trigger cellular responses, focusing on the differences between water-soluble peptide hormones and lipid-soluble steroid hormones, and on three signaling routes: Gs, Gq, and intracellular steroid-receptor signaling.

Peptide and steroid hormones use different receptor locations

• Peptide hormones are water-soluble and generally cannot pass through the cell’s lipid membrane. They bind to cell-surface receptors, which relay the signal inside through second messengers.
  • Examples include FSH, LH, growth hormone, glucagon, parathyroid hormone, insulin, oxytocin, and ADH.
• Steroid hormones are lipid-soluble and can diffuse through the membrane. They bind to intracellular receptors located in the cytosol or nucleus.
  • Examples include testosterone, estrogen, progesterone, aldosterone, and cortisol. In this context, the lecture also describes vitamin D and thyroxine as acting like steroid hormones.

Gs pathway: cAMP and protein kinase A

1. A hormone such as epinephrine binds to a G protein-coupled receptor (GPCR). The lecture describes GPCRs as seven-pass transmembrane receptors.
2. Receptor activation causes the stimulatory G protein to exchange GDP for GTP, switching it on.
3. The activated G protein stimulates adenylyl cyclase in the cell membrane.
4. Adenylyl cyclase converts ATP into cyclic AMP (cAMP).
5. cAMP activates protein kinases, which phosphorylate other proteins.
6. Depending on the target proteins and cell type, phosphorylation can alter ion-channel activity, metabolic pathways, gene-related processes, or cell growth.

The G protein’s GTPase activity converts GTP back to GDP, switching the G protein off.

Gq pathway: IP₃, DAG, and calcium

1. A hormone such as oxytocin binds to its GPCR and activates the Gq protein through GDP-to-GTP exchange.
2. Gq activates phospholipase C (PLC).
3. PLC cleaves membrane PIP₂ into two second messengers:
   • DAG activates protein kinase C (PKC), which phosphorylates target proteins.
   • IP₃ binds to receptors on the endoplasmic reticulum—or the sarcoplasmic reticulum in muscle—and prompts calcium release into the cytoplasm.
4. Calcium can bind calmodulin, activating kinases and other cellular responses. In muscle, calcium-dependent signaling can contribute to contraction.

The lecture highlights oxytocin’s role in raising intracellular calcium to support uterine contraction and milk ejection. It also mentions contraction in other tissues.

Steroid-hormone signaling inside the cell

1. A steroid hormone such as testosterone diffuses through the cell membrane.
2. It binds to an intracellular receptor in the cytosol or nucleus. The lecture describes unbound receptors as associated with heat shock proteins (HSPs).
3. Hormone binding displaces the heat shock proteins and activates the receptor.
4. The hormone–receptor complex binds a hormone response element (HRE) in DNA.
5. This can change gene transcription and protein production, with effects that may include altered metabolism, cell growth, or other cell functions.

Turning down signaling

• Phosphodiesterase (PDE) breaks down cAMP, helping limit or terminate cAMP signaling.
• Clarification: PLC cleaves PIP₂ into IP₃ and DAG; PDE does not break down PLC. The lecture’s wording suggesting that PDE degrades PLC is inaccurate.

Main takeaway

The receptor’s location and signaling mechanism depend on the hormone’s properties. Peptide hormones generally signal from the cell surface through second messengers, while steroid hormones can enter cells and regulate gene expression through intracellular receptors. The outcomes of either pathway depend on the proteins and functions of the target cell.

Speakers and sources

• Professor Zach Murphy, presenting for Ninja Nerd.
• No additional speakers are identified in the subtitles.