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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-08-0232v1 16/2/549    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vuorenoja, S. Articles by Rahman, N. Search for Related Content PubMed PubMed Citation Articles by Vuorenoja, S. Articles by Rahman, N.

S Vuorenoja, Physiology, University of Turku, Turku, Finland
B Mohanty, Physiology, University of Turku, Turku, Finland
J Arola, University of Helsinki, Department of Pathology, Helsinki, Finland
I Huhtaniemi, Department of Reproductive Biology, Imperial College, London, United Kingdom
J Toppari, Departments of Physiology and Pediatrics, University of Turku, Turku, Finland
N Rahman, Physiology, University of Turku, Turku, 20520, Finland

Correspondence: Nafis Rahman, Email: nafis.rahman{at}utu.fi

Abstract

Lytic peptide Hecate (23-AA) fused with a 15-AA fragment of human chorionic gonadotropin-β (CGβ), Hecate-CGβ conjugate (H-CGβ-c) selectively binds to and destroys tumor cells expressing luteinizing hormone/chorionic gonadotropin receptor (Lhcgr). Transgenic (TG) mice (6.5-month-old) expressing SV40 T-antigen under the inhibin promoter (inh/Tag) presenting with Lhcgr expressing adrenal tumors were treated either with H-CGβ-c, GnRH antagonist (GnRH-a), estradiol (E2) (only females) or their combinations for 1 month. We expected that GnRH-a or E2 in combination with H-CGβ-c could improve the treatment efficacy especially in females by decreasing circulating LH and eliminating the potential competition of serum LH with the H-CGβ-c. GnRH-a and H-CGβ-c treatments were successful in males (adrenal weights 14 +/- 2.8 mg and 60 +/- 26 mg vs. 237 +/- 59 mg in controls; p < 0.05). Histopathologically, GnRH-a apparently destroyed the adrenal parenchyma leaving only the fibrotic capsule with few necrotic foci. In females, H-CGβ-c was totally ineffective, whereas GnRH-a (19 +/- 5 mg) or E2 (77 +/- 50 mg) significantly reduced the adrenal weights compared to controls (330 +/- 70 mg). Adrenal morphometry, cell proliferation markers, post-treatment suppression of serum progesterone and qRT-PCR of GATA-4, Lhcgr and GATA-6 further supported the positive outcome. H-CGβ-c selectively killed the Lhcgr expressing tumor cells, whereas GnRH-a blocked tumor progression through gonadotrophin suppression, emphasizing the gonadotropin dependency of these adrenocortical tumors. If extrapolated to humans, H-CGβ-c could be considered for the treatment of gonadotropin-dependent adrenal tumors in males, whereas in females gonadotropin suppression, but not H-CGβ-c, would work better.

This article has been cited by other articles:

				N. A. Rahman and C.V. Rao Recent progress in luteinizing hormone/human chorionic gonadotrophin hormone research Mol. Hum. Reprod., November 1, 2009; 15(11): 703 - 711. [Abstract] [Full Text] [PDF]