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Novel functions of the luteinizing hormone/chorionic gonadotropin receptor in prostate cancer cells and patients

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  1. Inflammation, non-endothelial dependent coronary microvascular function and diastolic function-Are they linked?

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  2. Lipidomics of human adipose tissue reveals diversity between body areas

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  3. Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia

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  1. Longitudinal Increases in Serum Insulin-like Factor 3 and Testosterone Determined by LC-MS/MS in Pubertal Danish Boys

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  2. Marked Increase in Incident Gynecomastia: A 20-Year National Registry Study, 1998 to 2017

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  3. Grouping of endocrine disrupting chemicals for mixture risk assessment - Evidence from a rat study

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Prostate cancer (PCa) cells become castrate-resistant after initial tumor regression following castration-based lowering of testosterone (T). De-novo intra-tumoral steroid synthesis is a suggested biological mechanism of castration resistant PCa, but the regulators are unknown. Testicular T production is controlled by the luteinizing hormone/choriogonadotropin receptor (LHCGR). To elucidate the influence of LHCGR on PCa development the presence and effects of LHCGR in PCa and whether LHCGR in serum holds prognostic information in PCa patients is investigated. LHCGR expression was investigated by RT-PCR, WB, IHC, qPCR in PCa cell lines and prostatic tissue. Steroid production was measured in media from cell lines with LC-MS/MS and expression of steroidogenic enzymes with qPCR. Serum LHCGR (sLHCGR) was measured with ELISA in PCa patients (N = 157). Presence of LHCGR was established in prostatic tissue and PCa cell lines. Cell proliferation increased by 1.29-fold in LNCaP (P = 0.007) and 1.33-fold in PC-3 cells (P = 0.0007), when stimulated by luteinizing hormone. Choriogonadotropin stimulation decreased proliferation 0.93-fold in DU145 cells (P = 0.05), but none of the treatments altered steroid metabolite secretion. Low sLHCGR concentration was associated with a higher risk of biochemical failure after radical prostatectomy (HR = 3.05, P = 0.06) and castration resistance (HR = 6.92, P = 0.004) compared to high sLHCGR concentration. LHCGR is expressed in PCa and may exert a growth regulatory role in PCa derived cell lines. A potential prognostic role of sLHCGR for determining recurrence risk in PCa patients is found in this pilot study but needs verification in larger cohorts.

Original languageEnglish
JournalPLoS One
Volume15
Issue number9
Pages (from-to)e0238814
ISSN1932-6203
DOIs
Publication statusPublished - 3 Sep 2020

ID: 60879307