Myo-Inositol and D-Chiro-Inositol Reduce DHT-Stimulated Changes in the Steroidogenic Activity of Adult Granulosa Cell Tumors.

Autor: Wojciechowska AM; Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland., Zając P; Department of Physiology and Toxicology, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10-747 Olsztyn, Poland., Gogola-Mruk J; Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, 30-387 Krakow, Poland., Kowalik MK; Department of Physiology and Toxicology, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10-747 Olsztyn, Poland., Ptak A; Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, 30-387 Krakow, Poland.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Oct 12; Vol. 25 (20). Date of Electronic Publication: 2024 Oct 12.
DOI: 10.3390/ijms252010974
Abstrakt: 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.
Databáze: MEDLINE
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