Study data from X. Hu and co-authors update knowledge of life sciences
2009 JUN 22 - (NewsRx.com) -- According to a study from the United States, "ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), the phase 3 morbidity and mortality trial of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, identified previously undescribed changes in plasma levels of potassium, sodium, bicarbonate, and aldosterone. A key question after this trial is whether the failure of torcetrapib was a result of CETP inhibition or of some other pharmacology of the molecule." "The direct effects of torcetrapib and related molecules on adrenal steroid production were assessed in cell culture using the H295R as well as the newly developed HAC15 human adrenal carcinoma cell lines. Torcetrapib induced the synthesis of both aldosterone and cortisol in these two in vitro cell systems. Analysis of steroidogenic gene expression indicated that torcetrapib significantly induced the expression of CYP11B2 and CYP11B1, two enzymes in the last step of aldosterone and cortisol biosynthesis pathway, respectively. Transcription profiling indicated that torcetrapib and angiotensin II share overlapping pathways in regulating adrenal steroid biosynthesis. Hormone-induced steroid production is mainly mediated by two messengers, calcium and cAMP. An increase of intracellular calcium was observed after torcetrapib treatment, whereas cAMP was unchanged. Consistent with intracellular calcium being the key mediator of torcetrapib's effect in adrenal cells, calcium channel blockers completely blocked torcetrapib-induced corticoid release and calcium increase. A series of compounds structurally related to torcetrapib as well as structurally distinct compounds were profiled," wrote X. Hu and colleagues. The researchers concluded: "The results indicate that the pressor and adrenal effects observed with torcetrapib and related molecules are independent of CETP inhibition. (Endocrinology 150: 2211-2219, 2009)'." Hu and colleagues published their study in Endocrinology (Torcetrapib Induces Aldosterone and Cortisol Production by an Intracellular Calcium-Mediated Mechanism Independently of Cholesteryl Ester Transfer Protein Inhibition. Endocrinology, 2009;150(5):2211-2219). For more information, contact X. Hu, Pfizer Global Research & Development, 700 Chesterfield Pkwy W, Chesterfield, MO 63017, USA. Publisher contact information for the journal Endocrinology is: Endocrine Society, 8401 Connecticut Avenue, Suite 900, Chevy Chase, MD 20815-5817, USA. Keywords: United States, Chesterfield, Life Sciences, Adrenal Cancer, Adrenal Carcinoma, Oncology, Cardiology, Atherosclerosis, Pharmacology, Drugs, Therapies, Pharmaceuticals, Sodium Bicarbonate, Therapy, Treatment, Endocrinology. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.
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