A novel potential role of pituitary gonadotropins in the pathogenesis of human colorectal cancer

Abstract

BackgroundColorectal cancer (CRC) is a leading cause of death in the western world, and its incidence increases with patient age. It is also known that with age there occur changes in the levels of certain hormones, including an increase in the secretion of pituitary gonadotropins (PtGs) as a result of the loss of gonadal hormone feedback. We recently reported that functional PtG receptors are expressed in human lung cancer cells, rhabdomyosarcoma cells, and malignant hematopoietic stem cells.FindingsHere we report for the first time that the receptors for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are expressed in primary tumor samples isolated from CRC patients as well as in the established human CRC cell lines HTC116 and HTB37. Moreover, we also report that PtGs stimulate chemotaxis, adhesion, and proliferation of these cell lines.ConclusionsOur results suggest that PtGs play an important and underappreciated role in CRC pathogenesis, and we call for further studies to better define their role in gastrointestinal malignancies and their direct effect on putative CRC cancer stem cells.

Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis

“…Especially since the tumor growth reducing effect of cisplatin treatment also did not reach statistical significance compared with vehicle treatment, which indicates that even clinically relevant effects may be underestimated. The selected doses of LH and hCG in the in vitro and in vivo studies were based on previous studies investigating these drugs in cancer cell lines [ 20 , 21 ] and xenograft mouse models [ 21 , 22 ]. However, the use of nonequivalent doses of LH and hCG may explain the lack of effect of LH in vivo.…”

Gonadotropins as novel active partners in vascular diseases: Insight from angiogenic properties and thrombotic potential of endothelial colony‐forming cells

“…Twenty-four-well Transwell (Costar, Corning) and 8μm pore membranes coated with 0.2% gelatin for 30 min at 37°C were seeded with 1 × 10 4 ECFCs/well and filled up with endothelial cell basal medium-2 (EBM-2, Lonza, Basel, Switzerland) at the top and EBM-2 with or without gonadotropins at the bottom of the chamber. On the basis of previous studies, [8][9][10][11] we tested FSH or LH at 10, 100, 500, and 1000 µg/ml and PRL at 10, 100, 1000, and 10 000 µg/ml to obtain a dose-response curve. Vascular endothelial growth factor A (VEGF-A) at 50 ng/ml served as positive control as previously described.…”

Microbiome—The Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health

“…The CNS utilizes neural and endocrine pathways to cooperate with the gut. The sympathetic part of the autonomic nervous system and the hypothalamus-pituitary-adrenal axis (HPA) co-modulate the secretion, motility, and blood flow affecting intestinal permeability and influencing various GI disorders [35]. Gut neural signals are passed through the enteric nervous system (ENS) and the vagus nerve [36].…”