ラット副腎遊離束状層細胞におけるα-human atrial natriuretic polypeptideのコルチコステロン産生促進作用
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Several studies on the effects of atrial natriuretic polypeptide (ANP) on aldosterone production using isolated adrenal cells have been reported, and they have consistently demonstrated the reduced production of aldosterone by ANP. However, the results on the corticosterone production are sundry. Since ANP selectively activates particulate guanylate cyclase, a possibility could exist that cyclic GMP is the second messenger of ANP signal transduction. In order to demonstrate unequivocally a correlation of cyclic nucleotide levels with the ANP-induced steroidogenesis, we investigated the effects of various concentrations of a-human atrial natriuretic polypeptide (α-hANP) on aldosterone, corticosterone, cyclic AMP and cyclic GMP production in isolated glomerulosa and fasciculata cells of the rats. <BR>Rat glomerulosa and fasciculata cells were obtained by enzymatic digestion of the adrenals of male Wistar rats. The cell pellet was suspended in Hanks balanced salt solution 0.1% BSA buffer and distributed in 900μl aliquots to 12 × 75mm glass tubes. The samples were preincubated for 90 min. in a 37°C water bath under an atmosphere of 5% CO<SUB>2</SUB> /95% O<SUB>2</SUB>. Aliquots of the test samples were added in a 100μl volume and incubated for 4hr. Total volume of the incubation mixture is 1.0ml. Aldosterone, cyclic AMP and cyclic GMP were measured by radioimmunoassay and corticosterone was determined by fluorimetric method. <BR>The results indicated that α-hANP inhibited the secretion of aldosterone and corticosterone in rat glomerulosa cells. <BR>α-hANP significantly decreased cyclic AMP production in the rat glomerulosa cells, while it markedly stimulated cyclic GMP production. On the other hand, α-hANP increased concentrations of cyclic GMP, but not of cyclic AMP, in a dose-dependent manner with an increase in corticosterone production in the rat fasciculata cells. <BR>The role of cyclic GMP in steroidogenesis is controversial. Our findings suggest that cyclic GMP may play as the second messenger in α-hANP-induced steroidogenesis. Corticosterone production by α-hANP is a specific and intrinsic property of this peptide. In glomerulosa cell, corticosterone production was inhibited in spite of increased cyclic GMP production. <BR>Thus corticosterone production by α-hANP may be dependent on concentration of cyclic GMP. Our speculation is supported firmly by a study that ANP directly stimulates the membrane guanylate cyclase.
- 一般社団法人 日本内分泌学会の論文
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- ラット副腎遊離束状層細胞におけるα-human atrial natriuretic polypeptideのコルチコステロン産生促進作用