The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect

Zeynep Ağlamış; Nil Bita Entezari Ökeer; Sibel Süzen; Hande Gürer-orhan

The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect

Abstract

Melatonin (MLT) is a hormone that is secreted from pineal gland and regulates the circadian rhythm. It is reported to have anticancer effects in hormone dependent breast cancer via endocrine modulation, namely by antagonising the estrogen receptor (ER) or by inhibiting aromatase enzyme. However, its use is restricted because of its short half-life and poor bioavailability. Therefore, indole derived MLT analogues were synthesized previously, and they were shown to have potential antioxidant and anticancer effects. The present research is aimed to investigate the potential of MLT and its two newly synthesized analogues (M6 and M20) on steroidogenesis pathway by using an OECD validated in vitro method, H295R steroidogenesis assay (TG-456 test guideline). The compounds were incubated with H295R, human adenocarcinoma cells, for 48 hours and the hormone levels (testosterone; T and estradiol; E2) were detected by LC-MS/MS. The partial validation of the method was performed by using reference compounds forskolin, prochloraz, letrozole and ketoconazole. MLT decreased both E2 and T levels and its effect on E2 levels were dose dependent. On the other hand, M6 and M20 showed biphasic effects on both hormone levels. None of the compounds decreased H295R cell viability. These results demonstrate that depending on the use and the dose of these melatonin analogues, their potential effects on hormone production can result either in a therapeutical effect (such as anticancer agent) or a non-targeted endocrine related adverse effect when used as a pharmaceutical.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmaceutical Toxicology

Journal Section

Research Article

Authors

Zeynep Ağlamış This is me
0000-0002-2310-6321
Türkiye

Nil Bita Entezari Ökeer
0000-0003-1496-1091
Türkiye

Sibel Süzen
0000-0003-3413-6152
Türkiye

Hande Gürer-orhan ^*
0000-0002-4890-299X
Türkiye

Publication Date

June 27, 2025

Submission Date

September 2, 2022

Acceptance Date

December 15, 2022

Published in Issue

Year 2023 Volume: 27 Number: 2

IZ

https://izlik.org/JA72CG24RB

Cite

RIS / Bibtex

APA

Ağlamış, Z., Entezari Ökeer, N. B., Süzen, S., & Gürer-orhan, H. (2025). The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect. Journal of Research in Pharmacy, 27(2), 936-947. https://izlik.org/JA72CG24RB

AMA

1.Ağlamış Z, Entezari Ökeer NB, Süzen S, Gürer-orhan H. The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect. J. Res. Pharm. 2025;27(2):936-947. https://izlik.org/JA72CG24RB

Chicago

Ağlamış, Zeynep, Nil Bita Entezari Ökeer, Sibel Süzen, and Hande Gürer-orhan. 2025. “The Effects of Melatonin and Its Analogues on Steroidogenesis Pathway: A Possible Therapeutical or Adverse Effect”. Journal of Research in Pharmacy 27 (2): 936-47. https://izlik.org/JA72CG24RB.

EndNote

Ağlamış Z, Entezari Ökeer NB, Süzen S, Gürer-orhan H (June 1, 2025) The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect. Journal of Research in Pharmacy 27 2 936–947.

IEEE

[1]Z. Ağlamış, N. B. Entezari Ökeer, S. Süzen, and H. Gürer-orhan, “The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect”, J. Res. Pharm., vol. 27, no. 2, pp. 936–947, June 2025, [Online]. Available: https://izlik.org/JA72CG24RB

ISNAD

Ağlamış, Zeynep - Entezari Ökeer, Nil Bita - Süzen, Sibel - Gürer-orhan, Hande. “The Effects of Melatonin and Its Analogues on Steroidogenesis Pathway: A Possible Therapeutical or Adverse Effect”. Journal of Research in Pharmacy 27/2 (June 1, 2025): 936-947. https://izlik.org/JA72CG24RB.

JAMA

1.Ağlamış Z, Entezari Ökeer NB, Süzen S, Gürer-orhan H. The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect. J. Res. Pharm. 2025;27:936–947.

MLA

Ağlamış, Zeynep, et al. “The Effects of Melatonin and Its Analogues on Steroidogenesis Pathway: A Possible Therapeutical or Adverse Effect”. Journal of Research in Pharmacy, vol. 27, no. 2, June 2025, pp. 936-47, https://izlik.org/JA72CG24RB.

Vancouver

1.Zeynep Ağlamış, Nil Bita Entezari Ökeer, Sibel Süzen, Hande Gürer-orhan. The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect. J. Res. Pharm. [Internet]. 2025 Jun. 1;27(2):936-47. Available from: https://izlik.org/JA72CG24RB