CHEMICAL TRANSFORMATION OF STEROIDS BY ADRENAL PERFUSION: PERFUSION METHODS<sup>1</sup>

Hechter, Oscar; Jacobsen, Robert P.; Schenker, Victor; Levy, Harold; Jeanloz, Roger W.; Marshall, Charles; Pincus, Gregory; Scully, Ella; Johnson, Selma; Washburn, Irving E.; Rodgers, Orville G.; Maloney, Paul

doi:10.1210/endo-52-6-679

Cited by 47 publications

(15 citation statements)

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“…It is well known that in most secretory organs, the secretory products are stored in granules or vesicles, and release occurs by exocytosis. In the adrenal cortex, however, the presence of such intracellular organelles responsible for the storage of corticosteroid was not detected morphologically (35,36), and it has been reported that synthesized hormones diffuse out to the cell exterior (37,38). These results suggest that the site of taurine action on the release of adrenal secretory products may be primarily localized on storage granules, such as medullary granules for catecholamine.…”

Section: Discussionmentioning

confidence: 97%

Effect of Taurine on Alteration in Adrenal Functions Induced by Stress

Nakagawa

Kuriyama

1975

Jpn.J.Pharmacol

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Abstract-When rats were exposed to immobilized cold stress, adrenaline content in the adrenal gland as well as noradrenaline content in the brain stem were reduced drastically, while noradrenaline content in the atria was not altered by the application of stress. Oral administrations of taurine (4-7 g/kg/day, for 3 days) prevented the stress-induced decline of adrenaline in the adrenal gland and this preventive effect could not be duplicated by the administration of L-isoleucine or DL-methionine.In hypophysectomized rats, the stress also induced a significant fall in adrenaline content of the adrenal gland, however taurine administration did not show significant preven tive effects on the decline in adrenal catecholamines.The immobilized cold stress induced a significant increase in blood sugar and this increase was antagonized by pretreatment with taurine. Taurine had no significant effects on the stress-induced increase in the activity of adrenal tyrosine hydroxylase and the turnover rate of ad renaline in the adrenal gland measured by the rate of decline of this amine following (r-methyl-tyrosine administration.The administration of taurine, in both in I.iI.a and in vitro, inhibited the release of adrenaline from adrenal medullary granules, but that of dopamine-,.3-hydroxylase was not significantly affected. The stress-induced eleva tion of the blood level of corticosterone was not affected by taurine administration. These findings indicate that taurine antagonizes the stress-induced elevation of blood sugar by reducing adrenaline output from the adrenal gland. The regulatory mecha nism most likely involves the inhibition of adrenaline release from adrenal medullary granules, possibly by stabilizing the membrane of the granules.Numerous reports have shown that taurine (2-aminoethanesulfonic acid) inhibits the transmission of nerve impulses in a variety of mammalian and non-mammalian test pre parations (1-5).In addition, antagonistic effects of this compound against ouabain-induced (6) and cobalt-induced (7) seizures have been reported. On the other hand, a number of studies have demonstrated that urinary excretion of taurine is modified by the administration of ACTH (8, 9) or glucocorticoids (8, 10), and on the contrary taurine has a regulatory role in hormone secretion by varying the pituitary activity (11).In this study, we investigated the effect of taurine on the alteration of adrenal functions induced by immobilized stress in rats, with particular references to the effect on stress-induced alterations in the catecholamine release from the adrenal medulla. MATERIALS AND METHODSAnimal care: Male Wistar rats weighing 200-250 g were used throughout and were fasted for 20 hr before each experiment. Hypophysectornized rats were used 2 weeks after the operation. For the administration of various amino acids (taurine, L-isoleucine, and 738 K. NAKAGAWA & K. KURIYAMA DL-methionine), each amino acid was dissolved in drinking water (3% w/v) and provided act libitrrrn for 3 days. Average daily dose of each amino acid...

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Section: Discussionmentioning

confidence: 97%

Effect of Taurine on Alteration in Adrenal Functions Induced by Stress

Nakagawa

Kuriyama

1975

Jpn.J.Pharmacol

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“…However, both S. Lieberman's and our group were unable up to now to conclusively demonstrate the biosynthesis of pregnenolone in brain (3,4). Pregnenolone is the key steroid synthesized from cholesterol in steroidogenic glands (5,6). The oxidative side-chain cleavage of cholesterol is operated by a specific enzyme complex, which includes cytochrome P-450,CC (7).…”

mentioning

confidence: 87%

Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone.

Bourreau

Jung-Testas

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

234

129

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Oligodendrocyte mitochondria from 21-dayold Sprague-Dawley male rats were incubated with 100 nM[3lH]cholesterol. It yielded [3lH]pregnenolone at a rate of 2.5 ± 0.7 and 5-[3Hjpregnene-3fi,20a-diol at a rate of 2.5 ± 1.1 pmol per mg of protein per hr. Cultures of glial cells from 19-to 21-day-old fetuses (a mixed population of astrocytes and oligodendrocytes) were incubated for 24 hr with [3H]mevalonolactone.[3H]Cholesterol, [3H]pregnenolone, and 5-[3HJpreg-nene-3fi,20a-diol were characterized in cellular extracts. The formation of the 3H-labeled steroids was increased by dibutyryl cAMP (0.2 mM) added to the culture medium. The active cholesterol side-chain cleavage mechanism, recently suggested immunohistochemically and already observed in cultures of C6 glioma cells, reinforces the concept of "neurosteroids" applied to A5-3fi-hydroxysteroids previously isolated from brain.We have characterized two A5-3f3-hydroxysteroid metabolites of cholesterol, pregnenolone (3,8-hydroxy-5-pregnene-20-one) and dehydroepiandrosterone (3f3-hydroxy-5-androstene-17-one), in the brain of several mammalian species (rat, mouse, monkey, and occasionally pig and human). Definitive identification of the steroid moiety was made in rat brain extracts by gas/liquid chromatography-mass spectrometry (1-3). Pregnenolone has also been identified in acetone powder of rabbit brain by its mass spectrum (4). The A5-3p8-hydroxysteroids persisted in brain after removal of steroidogenic organs, and we therefore proposed that their formation or accumulation in the rat brain depends on in situ mechanisms unrelated to the peripheral endocrine gland system. However, both S. Lieberman's and our group were unable up to now to conclusively demonstrate the biosynthesis of pregnenolone in brain (3, 4). Pregnenolone is the key steroid synthesized from cholesterol in steroidogenic glands (5, 6). The oxidative side-chain cleavage of cholesterol is operated by a specific enzyme complex, which includes cytochrome P-450,CC (7). We have used specific antibodies to the bovine adrenal P-450 for the immunohistochemical localization of the enzyme in the adult rat brain, and we have found that the white matter was selectively immunostained throughout the brain (8 . The latter is a competitive inhibitor of 3,3-hydroxysteroid dehydrogenase activity, which might decrease pregnenolone levels in our experiments. The final protein concentration was 0.8 mg/ml for brain (corresponding to -30 x 106 cells) and 1-2 mg/ml for adrenal mitochondria.[3H]Cholesterol was added (5 x 106 cpm, 0.1 nmol) after suspension in 0.1 ml of Tris buffer (pH 7.4) containing 20 ,ug of Tween 80 (13). The reaction was initiated by the addition of 10 mM isocitrate to generate NADPH. Alternatively, a NADPHgenerating system was used: 0.75 mg of NADP+, 2.5 mg of glucose 6-phosphate, 0.5 unit of glucose-6-phosphate dehydrogenase (from Bakers' yeast; 260 units per mg of protein; Sigma), 95 ,g of MgCl2 in a total vol of 0.1 ml of phosphate buffer (0.1 M) (pH 7.4). The reaction was initiated by the *O...

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“…These data imply that adenylate cyclase and cyclic AMP-dependent protein kinase are obligatory components of the corticotropin-stimulated steroidogenic pathway. Corticotropin (ACTH) produces various responses in adrenocortical cells, the most notable being an increase in corticosteroid biosynthesis (1). Other responses include stimulation of adenylate cyclase activity with accumulation of cyclic AMP (2), depletion of cholesterol (3) and ascorbic acid content (4), stimulation of cholesterol esterase activity (5), and enhancement of glucose utilization (6).…”

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confidence: 99%

Mutations in cyclic AMP-dependent protein kinase and corticotropin (ACTH)-sensitive adenylate cyclase affect adrenal steroidogenesis.

Rae¹,

Gutmann²,

Tsao³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

141

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Two groups of mutant clones were isolated from Y1 adrenocortical tumor cells. One group, Y1(Kin), exhibited altered cytosolic cyclic AMP-dependent protein kinase activity; the second group, Y1(Cyc), exhibited diminished corticotropin-responsive adenylate cyclase activity. Steroidogenic responses to corticotropin and cyclic nucleotides closely paralleled cyclic AMP-dependent protein kinase activity in the YI(Kin) mutants. In Y1(Cyc) mutants, corticotropin had little effect on steroidogenesis, whereas cyclic nucleotides were fully active. These data imply that adenylate cyclase and cyclic

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CHEMICAL TRANSFORMATION OF STEROIDS BY ADRENAL PERFUSION: PERFUSION METHODS¹

Cited by 47 publications

References 0 publications

Effect of Taurine on Alteration in Adrenal Functions Induced by Stress

Effect of Taurine on Alteration in Adrenal Functions Induced by Stress

Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone.

Mutations in cyclic AMP-dependent protein kinase and corticotropin (ACTH)-sensitive adenylate cyclase affect adrenal steroidogenesis.

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CHEMICAL TRANSFORMATION OF STEROIDS BY ADRENAL PERFUSION: PERFUSION METHODS1

Cited by 47 publications

References 0 publications

Effect of Taurine on Alteration in Adrenal Functions Induced by Stress

Effect of Taurine on Alteration in Adrenal Functions Induced by Stress

Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone.

Mutations in cyclic AMP-dependent protein kinase and corticotropin (ACTH)-sensitive adenylate cyclase affect adrenal steroidogenesis.

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CHEMICAL TRANSFORMATION OF STEROIDS BY ADRENAL PERFUSION: PERFUSION METHODS¹