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Steroidogenesis activator polypeptide (SAP) in the guinea pig adrenal cortex
J Frustaci1, L M Mertz, R C Pedersen
1Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
Molecular and Cellular Endocrinology
|July 1, 1989
Summary
Steroidogenesis activator polypeptide (SAP) was isolated from guinea pig adrenal cortex. ACTH stimulation differentially increases SAP and cholesterol SCC activity in outer adrenal zones, explaining varied corticosteroid production.
Area of Science:
- Endocrinology
- Molecular Biology
- Adrenal Physiology
Background:
- Steroidogenesis activator polypeptide (SAP) stimulates cholesterol side-chain cleavage (SCC).
- SAP's role in differential adrenal zonation of steroidogenesis is unclear.
- Previous studies characterized SAP in rats.
Purpose of the Study:
- To isolate and characterize SAP from guinea pig adrenal cortex.
- To investigate the zonal distribution and regulation of SAP and cholesterol SCC activity.
- To elucidate the role of SAP in ACTH-mediated steroidogenesis in different adrenal zones.
Main Methods:
- Isolation of SAP from guinea pig adrenal cortex.
- Reverse-phase high-performance liquid chromatography (HPLC) and radioimmunoassay for SAP characterization.
- Two-dimensional immunoblotting for protein analysis (SAP, p82, cytochrome P-450scc).
- ACTH1-24 stimulation in dexamethasone-suppressed guinea pigs.
Main Results:
- Guinea pig SAP is biochemically similar to rat SAP.
- ACTH1-24 treatment significantly increased outer adrenal zone SAP (42-fold) and cholesterol SCC activity (2-fold).
- Inner adrenal zones showed minimal increases in SAP (4-fold) and no change in cholesterol SCC activity.
- A 82 kDa SAP precursor (p82) was detected, with no significant zonal or ACTH-dependent differences.
Conclusions:
- Differential ACTH-induced generation of SAP in outer adrenal zones correlates with enhanced cholesterol SCC activity.
- This zonal difference in SAP production likely explains the distinct corticosteroidogenic potentials of the zona fasciculata and zona reticularis.
- SAP plays a key role in regulating ACTH-stimulated steroidogenesis in a zone-specific manner.