EVIDENCE AGAINST AN INTERACTION OF ANGIOTENSIN II WITH THE SYMPATHETIC NERVOUS SYSTEM IN MAN

Animal experiments indicate that angiotensin II can, under some circumstances stimulate the sympathetic nervous system at a number of different sites. In order to determine whether such a relationship of the renin-angiotensin and sympathetic nervous system exists in man, we increased (by intravenous infusion), or decreased (by administering the oral converting enzyme inhibitor captopril) circulating angiotensin II levels and monitored plasma adrenaline and nor-adrenaline responses. Angiotensin II infusions did not increase plasma catechol-amines, and lowering of angiotensin II by captopril treatment in patients with severe hypertension or congestive heart failure failed to alter plasma adrenaline or nor-adrenaline levels. Whether physiological levels of angiotensin II are capable of interacting directly with the sympathetic nervous system in man remains to be demonstrated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73600/1/j.1365-2265.1981.tb00684.x.pd

Minor Abnormalities of Testis Development in Mice Lacking the Gene Encoding the MAPK Signalling Component, MAP3K1

In mammals, the Y chromosome is a dominant male determinant, causing the bipotential gonad to develop as a testis. Recently, cases of familial and spontaneous 46,XY disorders of sex development (DSD) have been attributed to mutations in the human gene encoding mitogen-activated protein kinase kinase kinase 1, MAP3K1, a component of the mitogen-activated protein kinase (MAPK) signal transduction pathway. In individuals harbouring heterozygous mutations in MAP3K1, dysregulation of MAPK signalling was observed in lymphoblastoid cell lines, suggesting a causal role for these mutations in disrupting XY sexual development. Mice lacking the cognate gene, Map3k1, are viable and exhibit the eyes open at birth (EOB) phenotype on a mixed genetic background, but on the C57BL/6J genetic background most mice die at around 14.5 dpc due to a failure of erythropoiesis in the fetal liver. However, no systematic examination of sexual development in Map3k1-deficient mice has been described, an omission that is especially relevant in the case of C57BL/6J, a genetic background that is sensitized to disruptions to testis determination. Here, we report that on a mixed genetic background mice lacking Map3k1 are fertile and exhibit no overt abnormalities of testis development. On C57BL/6J, significant non-viability is observed with very few animals surviving to adulthood. However, an examination of development in Map3k1-deficient XY embryos on this genetic background revealed no significant defects in testis determination, although minor abnormalities were observed, including an increase in gonadal length. Based on these observations, we conclude that MAP3K1 is not required for mouse testis determination. We discuss the significance of these data for the functional interpretation of sex-reversing MAP3K1 mutations in humans