Endocrine Influence on Cardiac Metabolism in Development and Regeneration

Mammalian cardiomyocytes mostly utilize oxidation of fatty acids to generate ATP. The fetal heart, in stark contrast, mostly uses anaerobic glycolysis. During perinatal development, thyroid hormone drives extensive metabolic remodeling in the heart for adaptation to extrauterine life. These changes coincide with critical functional maturation and exit of the cell cycle, making the heart a post-mitotic organ. Here, we review the current understanding on the perinatal shift in metabolism, hormonal status, and proliferative potential in cardiomyocytes. Thyroid hormone and glucocorticoids have roles in adult cardiac metabolism, and both pathways have been implicated as regulators of myocardial regeneration. We discuss the evidence that suggests these processes could be inter-related and how this can help explain variation in cardiac regeneration across ontogeny and phylogeny, and what breakthroughs are still to be made.

Regulation of atrial natriuretic peptide secretion by a novel Ras-like protein

Atrial cardiomyocytes, neurons, and endocrine tissues secrete neurotransmitters and peptide hormones via large dense-core vesicles (LDCVs). We describe a new member of the Ras family of G-proteins, named RRP17, which is expressed specifically in cardiomyocytes, neurons, and the pancreas. RRP17 interacts with Ca2+-activated protein for secretion-1 (CAPS1), one of only a few proteins known to be associated exclusively with LDCV exocytosis. Ectopic expression of RRP17 in cardiomyocytes enhances secretion of atrial natriuretic peptide (ANP), a regulator of blood pressure and natriuresis. Conversely, genetic deletion of RRP17 in mice results in dysmorphic LDCVs, impaired ANP secretion, and hypertension. These findings identify RRP17 as a component of the cellular machinery involved in regulated secretion within the heart and potential mediator of the endocrine influence of the heart on other tissues.

Cellular interactions in the hormonal induction of α2u-globulin in rat liver

ABSTRACT The role of hepatocellular interaction in the androgen-dependent synthesis of rat α2u-globulin was examined by immunochemical analysis of liver sections. Both after androgen administration to the ovariectomized female and during puberty in the male, only a subpopulation of hepatocytes became competent to synthesize α2u-globulin. These competent hepatocytes first appeared as discontinuous patches along the wall of the central vein. After the formation of a confluent layer around the central vein, cellular competency was seen to propagate toward the periportal direction through the cords of hepatic cells. Although the periportal progression of cellular competency for the synthesis of α2u-globulin appeared to be an all-or-none phenomenon, it did not require cell division. From these results we conclude that certain components of the central vein are necessary for the hormonal induction of α2u-globulin in the rat liver. We also propose that a primary endocrine influence on the hepatic vein results in the production of a secondary paracrine mediator which can trigger the synthesis of α2u-globulin in adjacent hepatocytes. Perivenous to periportal flow of this putative secondary mediator can explain cell recruitment for the synthesis of α2u-globulin along the hepatic cords. J. Endocr. (1986) 111, 205–208