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Preprocholecystokinin processing in the normal human anterior pituitary.
Summary
Human pituitary extracts reveal distinct cholecystokinin (CCK) processing. The anterior pituitary processes CCK into large fragments, while tumors mimic brain and gut processing of CCK into smaller peptides.
Area of Science:
- Endocrinology
- Molecular Biology
- Neuroscience
Background:
- The processing of precursor proteins into active peptides is crucial for hormone function.
- Cholecystokinin (CCK) is a peptide hormone with diverse physiological roles, but its processing in the human pituitary is not fully understood.
Purpose of the Study:
- To investigate the processing of preprocholecystokinin (preproCCK) in different regions of the human pituitary.
- To compare CCK processing in normal pituitary tissue with that in corticotrophic tumors.
Main Methods:
- Gel and ion-exchange chromatography were used to separate CCK peptides.
- Sequence-specific radioimmunoassays monitored CCK peptide levels.
- Enzymatic digestion with trypsin, carboxypeptidase B, and arylsulfatase was performed.
Main Results:
- The neural lobe predominantly contained bioactive alpha-amidated CCK peptides, with CCK-8 being the most abundant.
- The anterior lobe had large amounts of nonamidated procholecystokinin fragments and smaller amounts of alpha-amidated CCK in larger molecular forms (CCK-58, CCK-33).
- Corticotrophic tumors processed large CCK forms into smaller CCK-8-like peptides, similar to brain and gut processing.
Conclusions:
- Hormone gene expression can be limited to mature peptide production outside principal regions.
- The processing of CCK to smaller amidated peptides in less-differentiated tumor tissue supports the hypothesis of posttranslational regulation of endocrine cell differentiation.