INVESTIGADORES
CYMERYNG Cora Beatriz
artículos
Título:
Cytosolic and mitochondrial proteins as possible targets of cycloheximide effect on adrenal steroidogenesis
Autor/es:
DADA L; CORNEJO MACIEL, F; NEUMAN, I; MELE, PG; MALOBERTI, P; PAZ, C; CYMERYNG, CORA BEATRIZ; FINKIELSTEIN, C; MENDEZ, C; PODESTÁ, EJ
Revista:
ENDOCRINE RESEARCH
Editorial:
TAYLOR & FRANCIS INC
Referencias:
Año: 1996 vol. 22 p. 533 - 539
ISSN:
0743-5800
Resumen:
It is well accepted that protein(s) with a short
half-life are required in the pathway leading to steroid synthesis following
stimulation by trophic hormones. A correlation between the disappearance of
several proteins in different subcellular compartments and the inhibition of
steroid synthesis produced by cycloheximide (CHx) has also been shown. In the
present report we describe the effect of CHx in the stimulation of steroid
synthesis using a cell-free assay. Mitochondrial progesterone (P4) production
was studied by recombination of the different subcellular fractions of adrenal
zona fasciculata and determined by radioimmunoassay. Soluble factors from
ACTH-treated adrenals produced a four-fold stimulation of mitochondrial
steroidogenesis (3.0 +/- 0.6 vs. 13.3 +/- 0.5 ng P4/tube for control and
ACTH-treated adrenals respectively). Mitochondria obtained from CHx-ACTH-treated
adrenals fail to respond to soluble ACTH-dependent factors. A permeable
analogue of cholesterol (22(R)-OH cholesterol) could overcome the inhibition
imposed by CHx, confirming the role of mitochondrial proteins in
intramitochondrial cholesterol transport. The treatment of the adrenals with
CHx 10 minutes before ACTH administration abolished also the stimulation
induced by the cytosol on control mitochondria (2.6 +/- 0.5 vs. 13.0 +/- 1.0 ng
P4/tube for CHx-ACTH-treated cytosol vs. ACTH-treated cytosol). Arachidonic
acid (AA) added to CHx-ACTH-treated cytosol subdued this inhibition (10.3 +/-
1.2 ng P4/tube). CHx treatment had no effect on the stimulation by ACTH of the
cAMP-dependent protein kinase. These results indicate the involvement of a
cycloheximide-sensitive protein in the release of AA in adrenal
steroidogenesis.