Heme availability affects corticosterone and aldosterone biosynthesis in rat adrenal

Martini, Claudia; Avalos, Silvia G. Vaena de; Romero, Damián G.; Viale, L; Vila, María del Carmen

doi:10.1016/s0039-128x(97)00074-3

Cited by 8 publications

(6 citation statements)

References 14 publications

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“…These mechanisms may together result in a higher steroidogenic activity by supplying more reducing equivalents and heme to steroidogenic enzymes. This hypothesis is supported by previous observations indicating that heme availability limited adrenal corticosteroid biosynthesis [ 38 ] and by recent data showing that acute stimulation of steroid production by ACTH was significantly increased when heme oxygenase activity was inhibited [ 39 ].…”

Section: Discussionsupporting

confidence: 82%

Gene array and real time PCR analysis of the adrenal sensitivity to adrenocorticotropic hormone in pig

et al. 2008

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Background: Variability in hypothalamic-pituitary-adrenal (HPA) axis activity has been shown to be influenced by genetic factors and related to great metabolic differences such as obesity. The aim of this study was to investigate molecular bases of genetic variability of the adrenal sensitivity to ACTH, a major source of variability, in Meishan (MS) and Large White (LW) pigs, MS being reported to exhibit higher basal cortisol levels, response to ACTH and fatness than LW. A pig cDNA microarray was used to identify changes in gene expression in basal conditions and in response to ACTH stimulation.

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Section: Discussionsupporting

confidence: 82%

Gene array and real time PCR analysis of the adrenal sensitivity to adrenocorticotropic hormone in pig

et al. 2008

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“…Alas1 is the rate-limiting enzyme in heme biosynthesis and may serve to maintain a supply of heme for the prosthetic groups of the steroidogenic cytochrome P450s that are induced in response to ACTH. This hypothesis is supported by previous observations indicating that heme availability limits adrenal corticosteroid biosynthesis (35). Fads1 (36), Pank3 (37), and Mod1 (38) are all involved in aspects of intermediary metabolism, and in this general capacity may generate reduced nicotinamide adenine dinucleotide phosphate, a cofactor required for the mixed function oxidase activities of the steroidogenic cytochromes.…”

Section: ϫ ϫsupporting

confidence: 79%

Global Profiles of Gene Expression Induced by Adrenocorticotropin in Y1 Mouse Adrenal Cells

et al. 2006

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ACTH regulates the steroidogenic capacity, size, and structural integrity of the adrenal cortex through a series of actions involving changes in gene expression; however, only a limited number of ACTH-regulated genes have been identified, and these only partly account for the global effects of ACTH on the adrenal cortex. In this study, a National Institute on Aging 15K mouse cDNA microarray was used to identify genome-wide changes in gene expression after treatment of Y1 mouse adrenocortical cells with ACTH. ACTH affected the levels of 1275 annotated transcripts, of which 46% were up-regulated. The up-regulated transcripts were enriched for functions associated with steroid biosynthesis and metabolism; the down- regulated transcripts were enriched for functions associated with cell proliferation, nuclear transport and RNA processing, including alternative splicing. A total of 133 different transcripts, i.e. only 10% of the ACTH-affected transcripts, were represented in the categories above; most of these had not been described as ACTH-regulated previously. The contributions of protein kinase A and protein kinase C to these genome-wide effects of ACTH were evaluated in microarray experiments after treatment of Y1 cells and derivative protein kinase A-defective mutants with pharmacological probes of each pathway. Protein kinase A-dependent signaling accounted for 56% of the ACTH effect; protein kinase C-dependent signaling accounted for an additional 6%. These results indicate that ACTH affects the expression profile of Y1 adrenal cells principally through cAMP- and protein kinase A- dependent signaling. The large number of transcripts affected by ACTH anticipates a broader range of actions than previously appreciated.

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“…Consistently, we previously found that the synthesis from DOC of aldosterone, in calf and rat adrenal homogenates and the synthesis from DOC of corticosterone in rat adrenal homogenate, is increased about two fold by the in vitro addition of hemin (Martini et al, 1997). This would indicate that half of the cytochromes involved in these reactions, are in the apocytochrome form in basal condition.…”

Section: Discussionsupporting

confidence: 81%

“…We also reported that DDC, which inhibits ferrochelatase activity in rat adrenal, blocks ACTH-mediated aldosterone and corticosterone biosynthesis and heme partially restores the inhibition produced by DDC (Martini et al, 1997). These findings prove the requirement of heme synthesis for ACTH action.…”

Section: Introductionsupporting

confidence: 63%

Induction of 5-aminolevulinate synthase by activators of steroid biosynthesis

et al. 2007

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Heme availability affects corticosterone and aldosterone biosynthesis in rat adrenal

Cited by 8 publications

References 14 publications

Gene array and real time PCR analysis of the adrenal sensitivity to adrenocorticotropic hormone in pig

Gene array and real time PCR analysis of the adrenal sensitivity to adrenocorticotropic hormone in pig

Global Profiles of Gene Expression Induced by Adrenocorticotropin in Y1 Mouse Adrenal Cells

Induction of 5-aminolevulinate synthase by activators of steroid biosynthesis

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