[New steroid hormone family: endogenous cardiac glycosides and their role in physiologic and pathologic conditions].
In the last two decades extensive study has been carried out on the isolation, identification and biosynthesis of the "endogenous digitalis-like compounds" whose physiological and pathophysiological functions are only starting to be understood. Besides ouabain (strophanthin) and digoxin, four further endogenous cardiac glycosides were isolated and identified so far. These compounds are found in almost all mammalian tissues, including blood plasma and urine, but with the highest concentrations in the adrenal gland, pituitary and hypothalamus. De novo biosynthesis of these glycosides occurs in zona fasciculata cells of adrenal glands, precursors such as progesterone, pregnenolone, and rhamnose increase the synthesis of the ouabain-like immunoreactive material. The secretion of these compounds from the adrenocortical cells are controlled by adrenerg mechanisms, as well as via the renin-angiotensin system. The hydrophobic cardiac glycosides are transported in blood as complexes bound to specific binding globulins. The identified endogenous cardiac glycosides fulfill all the postulated criterions of the hormones, so they represent a new class of steroid hormones. The cardiac glycosides influence the active sodium pump, indirectly the intracellular free calcium concentration and therefore exert a positive inotropic effect on cardiac muscle. Furthermore, in physiological concentrations they can regulate the cell growth and protein synthesis inducing activation of intracellular signal pathways. Under pathological conditions, however, when the concentration of these steroids are high, they play a crucial role in the development of different serious illnesses such as essential hypertension as well as congestive heart failure. Further intensive investigations are needed to clarify some contradictory details accumulated during the last few years in this field.
Somogyi
János
J
Semmelweis Egyetem, Altalános Orvostudományi Kar, Orvosi Vegytani, Molekuláris Biológiai és Pathobiokémiai Intézet, Budapest.
Szalay
Júlia
J
Pándics
Tamás
T
Rosta
Klára
K
Csermely
Péter
P
Vér
Agota
A
D002301:Cardiac Glycosides / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism; D006728:Hormones / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D010042:Ouabain / Q000378:metabolism; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood / Q000378:metabolism
D002301:Cardiac Glycosides; D006728:Hormones; C028996:cardiac glycoside receptors; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase