Studies on Aldosterone Biosynthesis in Vitro^*

Abstract

Biosynthesis of 18-hydroxycorticosterone and aldosterone from corticosterone by bovine, guinea pig, and particularly sheep adrenal tissue has been studied. Both "18-hydroxylase" and "18-ol-dehydrogenase" were located mainly in the mitochondrial fraction.Reduced triphosphopyridine nucleotide (TPNH)and not reduced diphosphopyridine nucleotide (DPNH) was the cofactor for C-18 hydroxylation; presence of oxidized triphosphopyridine (TPN+) or diphosphopyridine nucleotide (DPN +) in the incubation media resulted in the conversion of 18-hydroxycorticosterone into 18-hydroxy-11 -dehydrocorticosterone and not into aldosterone. Ca2+ stimulated the conversion of corticosterone into 18-hydroxycorticosterone. SU 4885 [ 1,2-bis(3-pyridyl)-2-methyl-1 -propanone] and SU 9055 [3-(l ,2,3,4-tetrahydr-1 -oxo-2-naphthyl)pyri-P JL rogesterone, 11-deoxycorticosterone,* 1 *and corticosterone have been shown to be precursors of aldosterone biosynthesis (

Stimulation of Aldosterone Biosynthesis in Adrenal Mitochondria by Sodium Depletion*

“…The only step that is unique in the biosynthesis is the conversion of corticosterone to aldosterone, which occurs in the mitochondrial fraction (7)(8)(9). The steps involved are presumably corticosterone --18-hydroxycorticosterone --aldosterone.…”

Parallelism of 11β- and 18-Hydroxylation Demonstrated by Urinary Free Hormones in Man*

“…The inhibition by metyrapone of the 18-hydroxylation of DOC in man has been shown by Shoneshofer et al (16), and the inhibition of the 18-hydroxylation of B in vitro has been reported by several authors (17)(18)(19)(20). In some of these studies, 18-hydroxylation is reported to be more sensitive than ll/?-hydroxylation to the action of metyrapone (19)(20)(21).…”

Zur Beeinflussung der Aldosteronsekretion des Hundes durch veränderte Plasma-Magnesium-Konzentration

“…Der Einflu$ von Magnesium auf die Mineralocorticoidproduktion der Nebenniere ist nut wenig untersueht, obgleich bioehemisehe Befunde [14,15] Ver/~nderungen der Aldosteronsekretion ohne gleichartige VerKndenmgen der Cortieosteronsekretion spreehen ffir einen Einflu$ des Magnesiums auf einen sp/iten Syntheseschritt des Aldosterons. Bemerkenswert ist in diesem Zusammenhang eine mehrfaeh zu beobaehtende Ubereinstimmung der Magnesiumwirkung mit der yon Heparin: Eine erhShte Heparinkonzentration ffihrt an der Nebenniere nut in vivo, nicht in vitro zu einer isolierten Verminderung der Aldosteronsekretion durch Blockade eines sp/~ten Synthesesehritts yore Corticosteron zum Aldosteron (Cejka u.…”