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Myo-Inositol and D-Chiro-Inositol Reduce DHT-Stimulated Changes in the Steroidogenic Activity of Adult Granulosa Cell
Anna Maria Wojciechowska1, Paulina Zając2, Justyna Gogola-Mruk3
1Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
Abstract:
Considering the properties of myo-inositol (MI) and D-chiro-inositol (DCI), which are well known in polycystic ovary syndrome therapy, and the limitations of adult granulosa cell tumor (AGCT) treatment, especially for androgen-secreting tumors, we studied the role of MI and DCI in the androgen-rich environment of AGCTs. For this purpose, we analyzed the mRNA expression of steroidogenic genes and the secretion of progesterone (P4) and 17β-estradiol (E2) in an unstimulated and/or dihydrotestosterone (DHT)-stimulated environment under MI and DCI influence. Thus, we used the HGrC1 and KGN cell lines as in vitro models of healthy and cancerous granulosa cells. We found that DHT, the most potent androgen, increased E2 secretion and steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage gene (CYP11A1) mRNA expression without affecting 450 aromatase (CYP19A1) in AGCTs. However, after the MI and DCI treatment of KGN cells, both compounds strongly reduced StAR and CYP11A1 expression. Interestingly, in DHT-stimulated KGN cells, only DCI alone and its cotreatment with MI reduced both CYP11A1 mRNA and E2 secretion. These findings suggest that CYP11A1 is responsible for the antiestrogenic effect of DCI in the androgen-rich environment of AGCTs. Therefore, MI and DCI could be used as effective agents in the adjuvant treatment of AGCT, but further detailed studies are needed.
Insights
Myo-inositol (MI) and D-chiro-inositol (DCI) show potential in treating androgen-rich adult granulosa cell tumors (AGCTs). These compounds reduced key gene expression and estrogen secretion, suggesting a novel therapeutic avenue for AGCTs.
Area of Science:
- Endocrinology
- Oncology
- Reproductive Biology
Background:
- Adult granulosa cell tumors (AGCTs) present treatment challenges, particularly androgen-secreting variants.
- Myo-inositol (MI) and D-chiro-inositol (DCI) are recognized for their therapeutic roles in polycystic ovary syndrome.
- The impact of MI and DCI on the androgen-rich microenvironment of AGCTs remains understudied.
Purpose of the Study:
- To investigate the effects of MI and DCI on steroidogenesis in AGCTs.
- To analyze the influence of MI and DCI on gene expression and hormone secretion in an androgen-rich environment.
- To explore the potential of MI and DCI as adjuvant therapies for AGCT.
Main Methods:
- Utilized HGrC1 and KGN cell lines as in vitro models for healthy and cancerous granulosa cells.
- Assessed mRNA expression of key steroidogenic genes, including StAR and CYP11A1.
- Measured progesterone (P4) and 17β-estradiol (E2) secretion under various treatment conditions (unstimulated, DHT-stimulated, MI/DCI treatment).
Main Results:
- Dihydrotestosterone (DHT) stimulation increased E2 secretion and StAR/CYP11A1 mRNA expression in AGCT cells.
- Both MI and DCI treatment significantly reduced StAR and CYP11A1 expression in KGN cells.
- DCI, alone or with MI, notably decreased CYP11A1 mRNA and E2 secretion in DHT-stimulated KGN cells.
Conclusions:
- CYP11A1 appears to mediate the antiestrogenic effects of DCI in the context of AGCTs.
- MI and DCI demonstrate potential as effective agents for adjuvant therapy in AGCT.
- Further comprehensive research is warranted to validate these findings and clinical applicability.
