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P450 Side-Chain Cleavage Enzyme (P450-SCC) Is an Ovarian Autoantigen in a Mouse Model for Autoimmune Oophoritis
Zhi-Bin Tong1,2, Noriyuki Otsuka3,4, Wei Tu3,5
1Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA. tongz@mail.nih.gov.
Reproductive Sciences (Thousand Oaks, Calif.)
|May 18, 2022
Summary
Side-chain cleavage (P450-SCC) is identified as a key antigen in autoimmune oophoritis, a model for primary ovarian insufficiency. This finding suggests P450-SCC may play a similar role in human autoimmune POI.
Area of Science:
- Immunology
- Endocrinology
- Reproductive Biology
Background:
- Steroid-producing cells express cytochrome P450 enzymes crucial for hormone synthesis.
- These enzymes are implicated as antigens in autoimmune conditions like Addison's disease and primary ovarian insufficiency (POI).
- Autoimmune oophoritis in mice, induced by neonatal thymectomy, serves as a model for human autoimmune POI.
Purpose of the Study:
- To characterize ovarian steroid-producing cell antigens in a mouse model of autoimmune POI.
- To identify specific P450 enzymes involved in the autoimmune response against ovarian steroid-producing cells.
Main Methods:
- Indirect immunofluorescence staining of ovarian and adrenal tissues using sera from thymectomized mice.
- Production of recombinant steroidogenic enzymes: 17α-hydroxylase (17α-OH), P450-SCC, and 3β-hydroxysteroid dehydrogenase (3β-HSD).
- Immunoblotting assays to test antibody reactivity against recombinant proteins.
Main Results:
- Antibodies reacting with ovarian and adrenal steroid-producing cells were detected in over half of the thymectomized mice.
- All sera positive for steroid-producing cell antibodies reacted specifically with P450-SCC.
- No reactivity was observed with 17α-OH or 3β-HSD recombinant proteins, nor with sera from control mice.
Conclusions:
- P450-SCC is identified as a specific and major antigen in ovarian steroid-producing cells in this autoimmune oophoritis model.
- The findings suggest P450-SCC is a critical target antigen in autoimmune oophoritis.
- P450-SCC is hypothesized to play a similar role in human autoimmune POI due to conserved antigenicity.
