Journal of Steroid Biochemistry & Molecular Biology 115 (2009) 62–67 Contents lists available at ScienceDirect Journal of Steroid Biochemistry and Molecular Biology journal homepage: www.elsevier.com/locate/jsbmb Cholesterol synthesis in the lactating cow: Induced expression of candidate genes  Enrique Viturro ∗ , Matthias Koenning, Angelika Kroemer, Gregor Schlamberger, Steffi Wiedemann, Martin Kaske, Heinrich H.D. Meyer Physiology Weihenstephan, Technische Universitaet Muenchen, Weihenstephaner Berg 3, 85354 Freising, Germany article info Article history: Received 2 December 2008 Accepted 18 February 2009 Keywords: Cholesterol HMG-CoA reductase HMG-CoA synthase SREBP Scap abstract Despite the extensive knowledge for other species, cholesterol metabolism in ruminants is nowadays still not clear. Huge differences in milk cholesterol concentration are observed between breeds, managing strategies, individuals and moment of the lactating cycle, but the genetic actors working in the process of cholesterol secretion into milk have not been identified. As ruminant diet contains no cholesterol, understanding the mechanisms and regulation of synthesis, transport and secretion into milk is crucial when trying to reduce the amount of this metabolite in dairy products. The present work aims to study the expression of candidate genes for these processes in the liver of Bos taurus during the lactating cycle. Liver biopsies were obtained from 16 adult brown Swiss cows at different time points (2 weeks pre- partum and 0, 2, 4 and 8 weeks post-partum). After RNA extraction and reverse transcription, gene expression of candidate genes was studied using quantitative RT–PCR. Key enzymes of the choles- terol synthesis (3-hydroxy-methyglutaryl-coenzyme-A (HMG-CoA) synthase, HMG-CoA reductase and farnesyldiphosphat-farnesyltransferase (FDFT)) and gene expression feed-back regulators involved in lipid metabolism (sterol regulatory element binding proteins (SREBP1and 2) SREBP-cleavage activating protein (Scap) were selected as candidate genes. HMG-CoA-reductase and FDFT showed a huge expression increase until week 2 post-partum (p < 0.01), most probably in response to the new requirements in the mammary gland. As well, and as a possible explanation for such modifications, an increase in the expression of the regulators SREBP1 and Scap was observed (p < 0.01 and p < 0.05 respectively). Most important, the whole synthesis machinery showed a coordinated regulation, as highly significant positive correlations were found between the expression levels of the above mentioned enzymes (p <0.01). The increase of milk and blood cholesterol levels in B. taurus after parturition might be the result of a coordinated induction in the expression of key liver enzymes and their regulating factors. © 2009 Elsevier Ltd. All rights reserved. 1. Introduction Milk is not only a source of nutrients in form of lactose, proteins and lipids, it also serves as an important delivery medium for other crucial molecules, such as vitamins, minerals, bioactive lipids and cholesterol. The milk lipid fraction constitutes the major source of energy and is known to be extremely variable among species, rang- ing from a reported 0% in rhinoceros milk to as much as 50% in whales. In addition to that, total lipid content of the milk also varies within species, depending on such factors as feed [1] or stage of lactation [2].  This manuscript corresponds to a poster presented at the 18th Symposium of the Journal of Steroid Biochemistry and Molecular Biology in Seefeld, Austria. ∗ Corresponding author. Fax: +49 8161 714421. E-mail address: viturro@wzw.tum.de (E. Viturro). Particularly interesting among the milk lipid fraction is choles- terol, the major sterol in whole milk, with concentrations ranging 10–30 mg/dL (0.25–0.77 mM) [3]. This represents only 0.5% of the fat fraction, but because of the elevated consume of milk and dairy products in modern diet, these aliments range second on contribu- tion to daily cholesterol intake, especially among infants [4], with the well-known consequences for cardiovascular health in older ages. For attempting a reduction of this ingredient in this first-need aliment, it is necessary to completely understand the physiological mechanisms of its homeostasis in the lactating cow. Secretion of milk is a complicated process that depends on mobilisation of body reserves, endogenous synthesis and diet intake [5]. Taking into account that bovine diet will contain neg- ligible amounts of cholesterol and that the cholesterol reserves in cellular membranes may not cover the huge requirements of this substance in the mammary gland (until 8 g/day), it is possible to hypothesize that the endogenous synthesis of cholesterol may play 0960-0760/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.jsbmb.2009.02.011