ACTH-mediated glucocorticoid and mineralocorticoid production is inhibited by an inositolphosphoglycan and a glycosylphosphatidylinositol-phospholipase C is activated by the hormone in mammalian adrenocortical cells.
In the present paper, we report that an inositolphosphoglycan (IPG), derived from a Trypanosoma cruzi glycoinositolphosphoceramide (LPPG), is able to inhibit ACTH-mediated accumulation of a glucocorticoid, cortisol, in calf adrenocortical cells. This IPG is also able to inhibit the stimulation by ACTH of the production of the main glucocorticoid, corticosterone and the main mineralocorticoid, aldosterone, in rat adrenocortical cells. Nitrous acid deamination confirmed that IPG is responsible for this inhibition. In order to study the involvement of glycosylphosphatidylinositol (GPI) in ACTH response in rat adrenal cortex, the activation of a phospholipase that hydrolyzes GPI (GPI-PLC) was evaluated. It was found that the release of alkaline phosphatase, a GPI-anchored enzyme, to the extracellular medium is increased in rat adrenocortical cells by ACTH treatment. In addition, ACTH stimulates the release of ceramide from the glycoinositolphosphoceramide purified from T. cruzi. These data suggest that ACTH activates a GPI-PLC in rat adrenal cortex, which is in agreement with our previous data in calf adrenocortical cells; thus, the hydrolysis of GPI provoked by ACTH takes place in different mammals and the IPG released could inhibit ACTH-mediated synthesis of aldosterone, corticosterone and cortisol.
Vaena de Avalos
S
S
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina. silvae@qb.fcen.uba.ar
Lima
C
C
Martini
C
C
de Lederkremer
R M
RM
Vila
M C
MC
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D002417:Cattle; D003345:Corticosterone / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D005938:Glucocorticoids / Q000096:biosynthesis*; D006017:Glycolipids / Q000737:chemistry / Q000378:metabolism; D054800:Glycosylphosphatidylinositol Diacylglycerol-Lyase; D006854:Hydrocortisone / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008901:Mineralocorticoids / Q000096:biosynthesis*; D009844:Oligosaccharides / Q000494:pharmacology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D011134:Polysaccharides; D051381:Rats; D017207:Rats, Sprague-Dawley; D014349:Trypanosoma cruzi / Q000737:chemistry; D010738:Type C Phospholipases / Q000378:metabolism*
D005938:Glucocorticoids; D006017:Glycolipids; D007295:Inositol Phosphates; C111513:LPPG glycoinositolphosphoceramide; D008901:Mineralocorticoids; D009844:Oligosaccharides; D011134:Polysaccharides; C028039:inositol phosphate glycan; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054800:Glycosylphosphatidylinositol Diacylglycerol-Lyase; D003345:Corticosterone; D006854:Hydrocortisone