Related Experiment Video
Updated: Mar 15, 2026
11:27
Analysis of SCAP N-glycosylation and Trafficking in Human Cells
Published on: November 8, 2016
9.4K
SCAP/SREBP pathway is required for the full steroidogenic response to cyclic AMP
Masami Shimizu-Albergine1, Brian Van Yserloo2, Martin G Golkowski3
1School of Medicine, Department of Pharmacology, University of Washington, Seattle, WA 98195; School of Medicine, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA 98109; University of Washington Diabetes Institute, School of Medicine, University of Washington, Seattle, WA 98109;
Summary
Luteinizing hormone (LH) and cyclic AMP (cAMP) regulate steroidogenesis by activating the SCAP/SREBP pathway. SCAP is crucial for cholesterol synthesis and progesterone production in Leydig cells.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Luteinizing hormone (LH) stimulates steroidogenesis via cyclic AMP (cAMP).
- Cholesterol availability is critical for steroidogenesis, but its regulation by cAMP is unclear.
- The SCAP/SREBP pathway senses intracellular cholesterol levels.
Purpose of the Study:
- To investigate the role of SCAP (sterol-regulatory element-binding protein cleavage-activating protein) in LH/cAMP-mediated steroidogenesis.
- To determine if SCAP mediates cAMP-dependent regulation of cholesterol homeostasis and steroid production.
Main Methods:
- CRISPR-Cas9 gene editing to create SCAP-deficient MA10 Leydig cells.
- Inhibition of cAMP phosphodiesterases (PDE4 and PDE8) to mimic LH surge.
- Analysis of SCAP phosphorylation, SREBP2 activation, cholesterol gene expression, and progesterone production.
Main Results:
- SCAP deficiency prevented progesterone production induced by PDE inhibitors.
- PDE inhibitors increased SCAP phosphorylation and SREBP2 activation, leading to cholesterol gene expression.
- Reintroducing SCAP restored SREBP2 expression and partially rescued steroidogenic responses.
Conclusions:
- SCAP is essential for cAMP-stimulated steroidogenesis in Leydig cells.
- LH/cAMP signaling activates the SCAP/SREBP pathway to regulate cholesterol synthesis for steroid production.
- Steroidogenic cholesterol originates from both de novo synthesis and isoprenylation-dependent pathways.
Related Concept Videos
01:45Regulation of Nuclear Protein Sorting
3.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
01:28Global Regulatory Systems
840
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
840
01:25cAMP-dependent Protein Kinase Pathways
8.9K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.9K
01:31Transducer Mechanism: Nuclear Receptors
4.8K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
4.8K
01:24Intracellular Signaling Cascades
54.8K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
54.8K
01:26Signal Transduction: Overview
12.3K
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
12.3K