The roles of potassium and corticosteroids in determining the pattern of metabolism of [3H]deoxycorticosterone by monolayer cultures of rat adrenal zona glomerulosa cells

Peter J Hornsby, M. J. O'Hare

Research output: Contribution to journalArticle

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Abstract

The metabolism of [3H] deoxycorticosterone (DOC) by primary monolayer cultures of rat adrenal zona glomerulosa cells was studied under various conditions. The cells converted [3H]DOC to aldosterone, 18-hydroxycorticosterone (18OH-B), corticosterone and 18-hydroxycorticosterone (18OH-DOC). When the potassium concentration of the culture medium was 8, 12, 18 or 40 mM the pattern of metabolism of [3H]DOC was 'glomerulosa-like' i.e., the major products were aldosterone and 180H-B with corticosterone and 180H-DOC being minor metabolites. Treatment of the cells with 40 mM K+ resulted in a pattern of [3H]DOC metabolism where aldosterone and 180H-B accounted for >90% of the metabolites of the radioactive precursor; 180H-DOC was nearly undetectable. This pattern was maintained by raised K+ levels for at least 28 days, the duration of the experiments. With culture medium containing 4 mM K+, however, the pattern became 'fasciculata-like'; corticosterone and 180H-DOC were the major products with little aldosterone or 180H-B. The addition of 20 or 500 μM, but not 1 μM, monobutyryl cyclic AMP to glomerulosa cultures converted the 'glomerulosa-like'pattern of [3H]DOC metabolism to the 'fasciculata-like', as did also 55 μM aldosterone. The effects of these corticosteroids suggest that they may mediate the action of monobutyryl cyclic AMP. Since this cyclic AMP derivative did not reproduce the effects of high K+ on the pattern of [3H]DOC metabolism, it is probable that this long-term action of K+ on the glomerulosa cell is not mediated by intracellular cyclic AMP. Instead, we propose that there may be an important regulatory mechanism in the function of the glomerulosa cell which is directly sensitive to the intracellular K+ level and is inhibited by glucocorticoids. These characteristics suggest that this control point may involve protein synthesis.

Original languageEnglish (US)
Pages (from-to)997-1005
Number of pages9
JournalEndocrinology
Volume101
Issue number4
StatePublished - 1977
Externally publishedYes

Fingerprint

Zona Glomerulosa
Desoxycorticosterone
Potassium
Adrenal Cortex Hormones
Aldosterone
18-Hydroxycorticosterone
Corticosterone
Cyclic AMP
Culture Media
Glucocorticoids

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

The roles of potassium and corticosteroids in determining the pattern of metabolism of [3H]deoxycorticosterone by monolayer cultures of rat adrenal zona glomerulosa cells. / Hornsby, Peter J; O'Hare, M. J.

In: Endocrinology, Vol. 101, No. 4, 1977, p. 997-1005.

Research output: Contribution to journalArticle

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abstract = "The metabolism of [3H] deoxycorticosterone (DOC) by primary monolayer cultures of rat adrenal zona glomerulosa cells was studied under various conditions. The cells converted [3H]DOC to aldosterone, 18-hydroxycorticosterone (18OH-B), corticosterone and 18-hydroxycorticosterone (18OH-DOC). When the potassium concentration of the culture medium was 8, 12, 18 or 40 mM the pattern of metabolism of [3H]DOC was 'glomerulosa-like' i.e., the major products were aldosterone and 180H-B with corticosterone and 180H-DOC being minor metabolites. Treatment of the cells with 40 mM K+ resulted in a pattern of [3H]DOC metabolism where aldosterone and 180H-B accounted for >90{\%} of the metabolites of the radioactive precursor; 180H-DOC was nearly undetectable. This pattern was maintained by raised K+ levels for at least 28 days, the duration of the experiments. With culture medium containing 4 mM K+, however, the pattern became 'fasciculata-like'; corticosterone and 180H-DOC were the major products with little aldosterone or 180H-B. The addition of 20 or 500 μM, but not 1 μM, monobutyryl cyclic AMP to glomerulosa cultures converted the 'glomerulosa-like'pattern of [3H]DOC metabolism to the 'fasciculata-like', as did also 55 μM aldosterone. The effects of these corticosteroids suggest that they may mediate the action of monobutyryl cyclic AMP. Since this cyclic AMP derivative did not reproduce the effects of high K+ on the pattern of [3H]DOC metabolism, it is probable that this long-term action of K+ on the glomerulosa cell is not mediated by intracellular cyclic AMP. Instead, we propose that there may be an important regulatory mechanism in the function of the glomerulosa cell which is directly sensitive to the intracellular K+ level and is inhibited by glucocorticoids. These characteristics suggest that this control point may involve protein synthesis.",
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