Leukotrienes as common intermediates in the cyclic AMP dependent and independent pathways in adrenal steroidogenesis

Solang, Angela R.; Dada, Laura A.; Sardañons, Maria L.; Sánchez, Mercedes Leonor; Podestá, Ernesto J.

doi:10.1016/0022-4731(87)90145-2

Cited by 17 publications

(7 citation statements)

References 26 publications

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“…These findings contrast with the survival-promoting effect of high dietary ArA in larvae exposed only to handling and having relatively low basal cortisol levels. These authors hypothesized that a clue for those physiological mechanisms could be found in mammalian studies where not only prostaglandin E2 synthesized from the cyclooxygenase enzymes but other ArA metabolites, such as leukotrienes produced from the lipoxygenase enzyme system, also play an important role in ACTH secretion and adrenal steroidogenesis (121, 161).…”

Section: Endocrine and Neuroendocrine Effects Along Speciesmentioning

confidence: 99%

The Use of Dietary Additives in Fish Stress Mitigation: Comparative Endocrine and Physiological Responses

2019

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In the last years, studies on stress attenuation in fish have progressively grown. This is mainly due to the interest of institutions, producers, aquarists and consumers in improving the welfare of farmed fish. In addition to the development of new technologies to improve environmental conditions of cultured fish, the inclusion of beneficial additives in the daily meal in order to mitigate the stress response to typical stressors (netting, overcrowding, handling, etc.) has been an important research topic. Fish are a highly diverse paraphyletic group (over 27,000 species) though teleost infraclass include around 96% of fish species. Since those species are distributed world-wide, a high number of different habitats and vital requirements exist, including a wide range of environmental conditions determining specifically the stress response. Although the generalized endocrine response to stress (based on the release of catecholamines and corticosteroids) is detectable and therefore provides essential information, a high diversity of physiological effects have been described depending on species. Moreover, recent omics techniques have provided a powerful tool for detecting specific differences regarding the stress response. For instance, for transcriptomic approaches, the gene expression of neuropeptides and other proteins acting as hormonal precursors during stress has been assessed in some fish species. The use of different additives in fish diets to mitigate stress responses has been deeply studied. Besides the species factor, the additive type also plays a pivotal role in the differentiation of the stress response. In the literature, several types of feed supplements in different species have been assayed, deriving in a series of physiological responses which have not focused exclusively on the stress system. Immunological, nutritional and metabolic changes have been reported in these experiments, always associated to endocrine processes. The biochemical nature and physiological functionality of those feed additives strongly affect the stress response and, in fact, these can act as neurotransmitters or hormone precursors, energy substrates, cofactors and other essential elements, implying multi-systematic and multi-organic responses. In this review, the different physiological responses among fish species fed stress-attenuating diets based on biomolecules and minerals have been assessed, focusing on the endocrine regulation and its physiological effects.

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Section: Endocrine and Neuroendocrine Effects Along Speciesmentioning

confidence: 99%

The Use of Dietary Additives in Fish Stress Mitigation: Comparative Endocrine and Physiological Responses

2019

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“…AA plays a crucial role in the steroidogenic cells, mediating the induction of the steroidogenic acute regulatory (StAR) protein, one of the proteins involved in cholesterol transport [15–19]. Although it is clear from previous publications that AA plays its role in the process through the conversion to its lipoxygenated metabolites [15,17,20], a direct action of this fatty acid on cholesterol transport into the mitochondria cannot be ruled out.…”

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confidence: 99%

cAMP increases mitochondrial cholesterol transport through the induction of arachidonic acid release inside this organelle in Leydig cells

et al. 2006

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Arachidonic acid (AA) is a fatty acid with 20 carbons and four cis double bonds that are the source of its flexibility and its reactivity with molecular oxygen. The oxidation can happen nonenzymatically or through the action of three types of oxygenases: cyclooxygenase, lipoxygenase and cytochrome P450. Most of the effects of AA are attributable to its conversion by those enzymes to prostaglandins, leukotrienes and other bioactive products [1]. AA itself also has biological activity; however, the number of its described actions is reduced compared to the effects described for the AA metabolites. Moreover, it is not very well documented whether nonmetabolized AA is released and elicits special functions in a specific cellular compartment [2].Transport of long-chain fatty acids in cells definitely occurs when they are tightly linked to CoA by esterification catalyzed by acyl-CoA synthetases [3]. In mammalian and yeast cells [4] it appears that the acyl-CoA synthetases merely enhance uptake indirectly. Thus, formation of the polar CoA-ester effectively traps the fatty acid in the cell and functions as part of a facilitated distribution in different cellular compartments.The mechanisms involved in the compartmentalization of long-chain acyl-CoA esters and free fatty acids We have investigated the direct effect of arachidonic acid on cholesterol transport in intact cells or isolated mitochondria from steroidogenic cells and the effect of cyclic-AMP on the specific release of this fatty acid inside the mitochondria. We show for the first time that cyclic-AMP can regulate the release of arachidonic acid in a specialized compartment of MA-10 Leydig cells, e.g. the mitochondria, and that the fatty acid induces cholesterol transport through a mechanism different from the classical pathway. Arachidonic acid and arachidonoyl-CoA can stimulate cholesterol transport in isolated mitochondria from nonstimulated cells. The effect of arachidonoyl-CoA is inhibited by the reduction in the expression or in the activity of a mitochondrial thioesterase that uses arachidonoyl-CoA as a substrate to release arachidonic acid. cAMP-induced arachidonic acid accumulation into the mitochondria is also reduced when the mitochondrial thioesterase activity or expression is blocked. This new feature in the regulation of cholesterol transport by arachidonic acid and the release of arachidonic acid in specialized compartment of the cells could offer novel means for understanding the regulation of steroid synthesis but also would be important in other situations such as neuropathological disorders or oncology disorders, where cholesterol transport plays an important role.Abbreviations AA, arachidonic acid; AA-CoA, arachidonoyl-CoA; Acot2, mitochondrial acyl-CoA thioesterase; ACS4, acyl-CoA synthetase 4; BPB, 4-bromophenacyl bromide; 8Br-cAMP, 8-bromo-cAMP; CHX, cycloheximide; CPT1, carnitine-palmitoyl transferase 1; DBI, diazepam-binding inhibitor; NDGA, nordihydroguaiaretic acid; P450scc, cholesterol side-chain cleavage cytochrome P-450 enzyme; PBR...

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“…Several reports have shown that arachidonic acid (AA) and its metabolites play an essential role in the regulation of steroidogenesis and both the expression and function of StAR [17][18][19][20][21][22][23][24][25][26]. Adrenal cholesterol metabolism is inhibited by nordihydroguaiaretic acid (NDGA) [19][20][21][22][23][24][25], a lipoxygenase inhibitor that also acts as phospholipase A 2 inhibitor [27]. NDGA blocks the acute response of bovine cells to ACTH particularly when cAMP release is low [24], and it also decreases the expression of StAR mRNA in rodent steroidogenic cells [23,25,26].…”

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confidence: 99%

“…Although the role of AA in trophic hormone-stimulated steroid production in various steroidogenic cells is well documented [17][18][19][20][21][22][23][24][25][26], the mechanism responsible for the release of AA remains unknown. Previous studies have reported that phospholipase A 2 (PLA 2 ) inhibitors abrogate the effect of LH-and ACTH-stimulated steroid production thereby suggesting the involvement of PLA 2 in the mechanism of action of trophic hormones [18,19,23].…”

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confidence: 99%

Concerted regulation of free arachidonic acid and hormone‐induced steroid synthesis by acyl‐CoA thioesterases and acyl‐CoA synthetases in adrenal cells

Maloberti

Lozano

Mele

et al. 2002

European Journal of Biochemistry

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Although the role of arachidonic acid (AA) in the regulation of steroidogenesis is well documented, the mechanism for AA release is not clear. Therefore, the aim of this study was to characterize the role of an acyl-CoA thioesterase (ARTISt) and an acyl-CoA synthetase as members of an alternative pathway in the regulation of the intracellular levels of AA in steroidogenesis. Purified recombinant ARTISt releases AA from arachidonoyl-CoA (AA-CoA) with a K m of 2 lM. Antibodies raised against recombinant acyl-CoA thioesterase recognize the endogenous protein in both adrenal tissue and Y1 adrenal tumor cells by immunohistochemistry and immunocytochemistry and Western blot. Stimulation of Y1 cells with ACTH significantly stimulated endogenous mitochondrial thioesterases activity (1.8-fold). Nordihydroguaiaretic acid (NDGA), an inhibitor of AA release known to affect steroidogenesis, affects the in vitro activity of recombinant ARTISt and also the endogenous mitochondrial acyl-CoA thioesterases. ACTH-stimulated steroid synthesis in Y1 cells was significantly inhibited by a synergistic effect of NDGA and triacsin C an inhibitor of the AA-CoA synthetase. The apparent IC 50 for NDGA was reduced from 50 lM to 25, 7.5 and 4.5 lM in the presence of 0.1, 0.5 and 2 lM triacsin C, respectively. Our results strongly support the existence of a new pathway of AA release that operates in the regulation of steroid synthesis in adrenal cells.

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Leukotrienes as common intermediates in the cyclic AMP dependent and independent pathways in adrenal steroidogenesis

Cited by 17 publications

References 26 publications

The Use of Dietary Additives in Fish Stress Mitigation: Comparative Endocrine and Physiological Responses

The Use of Dietary Additives in Fish Stress Mitigation: Comparative Endocrine and Physiological Responses

cAMP increases mitochondrial cholesterol transport through the induction of arachidonic acid release inside this organelle in Leydig cells

Concerted regulation of free arachidonic acid and hormone‐induced steroid synthesis by acyl‐CoA thioesterases and acyl‐CoA synthetases in adrenal cells

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