Gonadotropin releasing hormone antagonist treatment induces cell cycle arrest in gonadal somatic cell and adrenocortical tumours

Milena Doroszko; Marcin Chrusciel; Ilpo Huhtaniemi; Jorma Toppari; Nafis Rahman

doi:10.1530/endoabs.37.EP1134

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Endocrine Abstracts (2015) 37 EP1134 | DOI: 10.1530/endoabs.37.EP1134

ECE2015 Eposter Presentations Endocrine tumours (69 abstracts)

Gonadotropin releasing hormone antagonist treatment induces cell cycle arrest in gonadal somatic cell and adrenocortical tumours

Milena Doroszko ¹ , Marcin Chrusciel ¹ , Ilpo Huhtaniemi ^1, , Jorma Toppari ^1, & Nafis Rahman ^1,

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¹Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland; ²Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; ³Department of Surgery and Cancer, Imperial College London, Faculty of Medicine, London, UK; ⁴Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Bialystok, Poland.

We have earlier shown that treatment with gonadotropin releasing hormone antagonist blocked adrenocortical tumour progression through gonadotropin suppression in inhibin α/SV40 T-antigen (inhα/Tag) transgenic (TG) mice. Hereby, we investigated the molecular mechanisms underlying the GnRH antagonist (Cetrorelix acetate; GnRH-a) treatment induced potential antitumor effects on gonadal somatic cell and adrenocortical tumors in vivo and in vitro. In vitro treatment with 10 μM GnRH-a significantly decreased cell viability and proliferation of murine KK1 (granulosa cell), BLT1 (Leydig cell), Cα1 (adrenocortical), all three lines originating from inhα/Tag mice tumors, compared to respective non-treated controls. Flow cytometric analysis revealed a cell cycle arrest at G1 phase in all treated cell lines. We treated in vivo 6-mo-old inhα/Tag mice bearing gonadal or 6.5-mo-old mice bearing adrenal tumors for 21 days, with either 3 mg/kg b.w./48 h i.p. of GnRH-a or vehicle. Treatments revealed a significant reduction of tumor burden in all types of tumours with GnRH-a treatment vs vehicle treated group. Our results suggest that GnRH-a treatment, besides blocking the release of gonadotropins, may also directly induce tumour cell death.

Disclosure: Singrid Juselius Foundation

Academy of Finland