Localization and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1) in the adult rat kidney
Cumulative evidence demonstrated effective downstream metabolism of pregnenolone in renal tissue. The aim of this study was to evaluate the expression and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1), which converts cholesterol into pregnenolone, in adult rat kidney. I...
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todo:paper_03037207_v332_n1-2_p253_Pagotto2023-10-03T15:19:53Z Localization and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1) in the adult rat kidney Pagotto, M.A. Roldán, M.L. Pagotto, R.M. Lugano, M.C. Pisani, G.B. Rogic, G. Molinas, S.M. Trumper, L. Pignataro, O.P. Monasterolo, L.A. CYP11A1 Kidney Mitochondria Pregnenolone Steroidogenesis cholesterol monooxygenase (side chain cleaving) messenger RNA pregnenolone steroidogenic acute regulatory protein animal cell animal tissue article cell isolation cholesterol metabolism cholesterol transport controlled study enzyme activity enzyme localization Henle loop intracellular transport kidney kidney cortex kidney distal tubule kidney function kidney medulla kidney structure male mitochondrial membrane nonhuman priority journal progesterone synthesis protein expression protein function rat steroidogenesis tissue distribution tissue level Animals Carrier Proteins Cholesterol Side-Chain Cleavage Enzyme Kidney Male Mitochondrial Membranes Phosphoproteins Pregnenolone Progesterone Rats Rats, Wistar Receptors, GABA-A Testosterone Cumulative evidence demonstrated effective downstream metabolism of pregnenolone in renal tissue. The aim of this study was to evaluate the expression and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1), which converts cholesterol into pregnenolone, in adult rat kidney. Immunohistochemical labeling for CYP11A1 was observed in renal cortex and medulla, on structures identified as distal convoluted tubule and thick ascending limb of Henle's loop, respectively. Immunoblotting analysis corroborated the renal expression of the protein in inner mitochondrial membrane fractions. The incubation of isolated mitochondria with the membrane-permeant cholesterol analogue 22R-hydroxycholesterol resulted in efficient formation of pregnenolone, the immediate precursor for the synthesis of all the steroid hormones. The low progesterone production rate observed in these experiments suggested a poor activity of 3β-hydroxysteroid dehydrogenase enzyme in renal mitochondria. The steroidogenic acute regulatory protein (StAR), involved in the mitochondrial import of cholesterol, was detected in renal tissue at both mRNA and protein level. Immunostaining for StAR showed similar distribution to that observed for CYP11A1. The expression of StAR and CYP11A1 was found to be higher in medulla than in cortex. This enhanced expression of steroidogenesis-related proteins correlated with a greater pregnenolone synthesis rate and higher steroid hormones tissular content measured in medulla. In conclusion, we have established the expression and localization of StAR and CYP11A1 protein, the ability of synthesizing pregnenolone and a region-specific content of sex hormones in the adult rat kidney. These data clearly show that the kidney is a steroid hormones synthesizing organ. It is proposed that the existence in the kidney of complete steroidogenic machinery would respond to a physiological significance. © 2010 Elsevier Ireland Ltd. Fil:Pagotto, R.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pignataro, O.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03037207_v332_n1-2_p253_Pagotto |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
CYP11A1 Kidney Mitochondria Pregnenolone Steroidogenesis cholesterol monooxygenase (side chain cleaving) messenger RNA pregnenolone steroidogenic acute regulatory protein animal cell animal tissue article cell isolation cholesterol metabolism cholesterol transport controlled study enzyme activity enzyme localization Henle loop intracellular transport kidney kidney cortex kidney distal tubule kidney function kidney medulla kidney structure male mitochondrial membrane nonhuman priority journal progesterone synthesis protein expression protein function rat steroidogenesis tissue distribution tissue level Animals Carrier Proteins Cholesterol Side-Chain Cleavage Enzyme Kidney Male Mitochondrial Membranes Phosphoproteins Pregnenolone Progesterone Rats Rats, Wistar Receptors, GABA-A Testosterone |
| spellingShingle |
CYP11A1 Kidney Mitochondria Pregnenolone Steroidogenesis cholesterol monooxygenase (side chain cleaving) messenger RNA pregnenolone steroidogenic acute regulatory protein animal cell animal tissue article cell isolation cholesterol metabolism cholesterol transport controlled study enzyme activity enzyme localization Henle loop intracellular transport kidney kidney cortex kidney distal tubule kidney function kidney medulla kidney structure male mitochondrial membrane nonhuman priority journal progesterone synthesis protein expression protein function rat steroidogenesis tissue distribution tissue level Animals Carrier Proteins Cholesterol Side-Chain Cleavage Enzyme Kidney Male Mitochondrial Membranes Phosphoproteins Pregnenolone Progesterone Rats Rats, Wistar Receptors, GABA-A Testosterone Pagotto, M.A. Roldán, M.L. Pagotto, R.M. Lugano, M.C. Pisani, G.B. Rogic, G. Molinas, S.M. Trumper, L. Pignataro, O.P. Monasterolo, L.A. Localization and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1) in the adult rat kidney |
| topic_facet |
CYP11A1 Kidney Mitochondria Pregnenolone Steroidogenesis cholesterol monooxygenase (side chain cleaving) messenger RNA pregnenolone steroidogenic acute regulatory protein animal cell animal tissue article cell isolation cholesterol metabolism cholesterol transport controlled study enzyme activity enzyme localization Henle loop intracellular transport kidney kidney cortex kidney distal tubule kidney function kidney medulla kidney structure male mitochondrial membrane nonhuman priority journal progesterone synthesis protein expression protein function rat steroidogenesis tissue distribution tissue level Animals Carrier Proteins Cholesterol Side-Chain Cleavage Enzyme Kidney Male Mitochondrial Membranes Phosphoproteins Pregnenolone Progesterone Rats Rats, Wistar Receptors, GABA-A Testosterone |
| description |
Cumulative evidence demonstrated effective downstream metabolism of pregnenolone in renal tissue. The aim of this study was to evaluate the expression and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1), which converts cholesterol into pregnenolone, in adult rat kidney. Immunohistochemical labeling for CYP11A1 was observed in renal cortex and medulla, on structures identified as distal convoluted tubule and thick ascending limb of Henle's loop, respectively. Immunoblotting analysis corroborated the renal expression of the protein in inner mitochondrial membrane fractions. The incubation of isolated mitochondria with the membrane-permeant cholesterol analogue 22R-hydroxycholesterol resulted in efficient formation of pregnenolone, the immediate precursor for the synthesis of all the steroid hormones. The low progesterone production rate observed in these experiments suggested a poor activity of 3β-hydroxysteroid dehydrogenase enzyme in renal mitochondria. The steroidogenic acute regulatory protein (StAR), involved in the mitochondrial import of cholesterol, was detected in renal tissue at both mRNA and protein level. Immunostaining for StAR showed similar distribution to that observed for CYP11A1. The expression of StAR and CYP11A1 was found to be higher in medulla than in cortex. This enhanced expression of steroidogenesis-related proteins correlated with a greater pregnenolone synthesis rate and higher steroid hormones tissular content measured in medulla. In conclusion, we have established the expression and localization of StAR and CYP11A1 protein, the ability of synthesizing pregnenolone and a region-specific content of sex hormones in the adult rat kidney. These data clearly show that the kidney is a steroid hormones synthesizing organ. It is proposed that the existence in the kidney of complete steroidogenic machinery would respond to a physiological significance. © 2010 Elsevier Ireland Ltd. |
| format |
JOUR |
| author |
Pagotto, M.A. Roldán, M.L. Pagotto, R.M. Lugano, M.C. Pisani, G.B. Rogic, G. Molinas, S.M. Trumper, L. Pignataro, O.P. Monasterolo, L.A. |
| author_facet |
Pagotto, M.A. Roldán, M.L. Pagotto, R.M. Lugano, M.C. Pisani, G.B. Rogic, G. Molinas, S.M. Trumper, L. Pignataro, O.P. Monasterolo, L.A. |
| author_sort |
Pagotto, M.A. |
| title |
Localization and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1) in the adult rat kidney |
| title_short |
Localization and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1) in the adult rat kidney |
| title_full |
Localization and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1) in the adult rat kidney |
| title_fullStr |
Localization and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1) in the adult rat kidney |
| title_full_unstemmed |
Localization and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1) in the adult rat kidney |
| title_sort |
localization and functional activity of cytochrome p450 side chain cleavage enzyme (cyp11a1) in the adult rat kidney |
| url |
http://hdl.handle.net/20.500.12110/paper_03037207_v332_n1-2_p253_Pagotto |
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