Correlation Networks Provide New Insights into the Architecture of Testicular Steroid Pathways in Pigs

Steroid metabolism is a fundamental process in the porcine testis to provide testosterone but also estrogens and androstenone, which are essential for the physiology of the boar. This study concerns boars at an early stage of puberty. Using a RT-qPCR approach, we showed that the transcriptional activities of several genes providing key enzymes involved in this metabolism (such as CYP11A1) are correlated. Surprisingly, HSD17B3, a key gene for testosterone production, was absent from this group. An additional weighted gene co-expression network analysis was performed on two large sets of mRNA-seq to identify co-expression modules. Of these modules, two containing either CYP11A1 or HSD17B3 were further analyzed. This comprehensive correlation meta-analysis identified a group of 85 genes with CYP11A1 as hub gene, but did not allow the characterization of a robust correlation network around HSD17B3. As the CYP11A1-group includes most of the genes involved in steroid synthesis pathways (including LHCGR encoding for the LH receptor), it may control the synthesis of most of the testicular steroids. The independent expression of HSD17B3 probably allows part of the production of testosterone to escape this control. This CYP11A1-group contained also INSL3 and AGT genes encoding a peptide hormone and an angiotensin peptide precursor, respectively.

Angiotensin-(1-7) attenuates hypertension and cardiac hypertrophy via modulation of nitric oxide and neurotransmitter levels in the paraventricular nucleus in salt-sensitive hypertensive rats

Angiotensin-(1-7) [Ang-(1-7)] is a multifunctional bioactive angiotensin peptide which exerts a cardiovascular protective function mainly by opposing the effects of angiotensin II.

Abstract 561: The ex vivo RAS-Fingerprint - A Novel Approach for the Biochemical Chatracterization of the Renin-Angiotensin-System in Clinical Samples

Angiotensin concentrations are affected by multiple molecular components including receptors and enzymes which might be either dissolved in plasma or attached to blood cells or endothelial surfaces throughout the body, giving rise to a concentration determining local enzymatic environment. This environment substantially changes during blood collection leading to a rapid and fundamental shift in angiotensin peptide levels. Therefore, a clearly defined and properly controlled sample stabilization procedure is essential for the accurate measurement of in vivo angiotensin peptide levels. Surprisingly, standard samples collected by anti-coagulation with heparin can be used for analyzing the human RAS under well-defined steady-state conditions, allowing RAS-Fingerprint based conclusions about the activities of circulating enzymes involved in angiotensin metabolism. The mass spectrometry based measurements of in vivo RAS-Fingerprints (immediate sample stabilization) or heparin plasma derived ex vivo RAS-Fingerprints in plasma or whole blood provide unique insights into the physiology of the human RAS. RAS-Fingerprinting provides an integrated view about the activity of the enzymes involved in angiotensin metabolism in a plasma sample and therefore represents a powerful tool for characterization of the patient specific “Biochemical Hardware”, which determines angiotensin peptide levels in vivo. The assay is compatible with undiluted plasma and whole blood and can be further applied to long-term stored frozen plasma samples. The utilization of RAS-Fingerprinting in clinical studies will substantially enhance our understanding of the human RAS and could lead to the development of personalized approaches for the treatment and prevention of cardiovascular diseases in the near future.