Loss of expression of a differentiated function gene, steroid 17α-hydroxylase, as adrenocortical cells senesce in culture

P. J. Hornsby, J. P. Hancock, T. P. Vo, L. M. Nason, R. F. Ryan, J. M. McAllister

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Abstract

Senescence in cultured adrenocortical cells involves changes in expression of differentiated functions as well as changes in responses to mitogenic stimulation. Steroid 17α-hydroxylase (steroid 17α-monooxygenase, EC 1.14.99.9) is an adrenal-specific enzyme, the expression of which is dependent on the presence of stimulators of cyclic AMP production, such as cholera toxin. Dot-blot hybridization of RNA from bovine adrenocortical cells that had been incubated with cholera toxin showed a marked decline in 17α-hydroxylase mRNA levels as a function of population doubling level, closely paralleling the decline in induction of 17α-hydroxylase enzyme activity. The lower levels of 17α-hydroxylase induction did not result from a requirement for a longer time period for induction or from a specific defect in response to cholera toxin and were not caused by a general failure of enzyme induction in response to cyclic AMP. The decreased growth rate in older cells result from a general decline in response to several growth factors. However, the decline in 17α-hydroxylase induction did not result from a loss of response of the cells to mitogens, since quiescent cells at a low population doubling level showed stimulation of 17α-hydroxylase mRNA by cholera toxin to levels similar to those in nonquiescent cultures and added mitogens either had no effect on 17α-hydroxylase mRNA levels or decreased them. There was, however, a specific posttranscriptional effect of insulin on 17α-hydroxylase. The loss of 17α-hydroxylase induction is unlikely to result from overgrowth of a minority cell type lacking the ability to induce 17α-hydroxylase, because adrenocortical cell clones that had high levels of 17α-hydroxylase induction gave rise to cells with lower levels of induction on subcloning. Thus, loss of 17α-hydroxylase activity in adrenocortical cellular senescence results from a primary failure of accumulation of 17α-hydroxylase mRNA after incubation with the inducing agent.

Original languageEnglish (US)
Pages (from-to)1580-1584
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume84
Issue number6
DOIs
StatePublished - Jun 30 1987

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Steroid 17-alpha-Hydroxylase
Mixed Function Oxygenases
Genes
Cholera Toxin
Messenger RNA
Mitogens
Cyclic AMP
Enzyme Induction
Cell Aging
Enzymes
Population
Cultured Cells
Intercellular Signaling Peptides and Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

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title = "Loss of expression of a differentiated function gene, steroid 17α-hydroxylase, as adrenocortical cells senesce in culture",
abstract = "Senescence in cultured adrenocortical cells involves changes in expression of differentiated functions as well as changes in responses to mitogenic stimulation. Steroid 17α-hydroxylase (steroid 17α-monooxygenase, EC 1.14.99.9) is an adrenal-specific enzyme, the expression of which is dependent on the presence of stimulators of cyclic AMP production, such as cholera toxin. Dot-blot hybridization of RNA from bovine adrenocortical cells that had been incubated with cholera toxin showed a marked decline in 17α-hydroxylase mRNA levels as a function of population doubling level, closely paralleling the decline in induction of 17α-hydroxylase enzyme activity. The lower levels of 17α-hydroxylase induction did not result from a requirement for a longer time period for induction or from a specific defect in response to cholera toxin and were not caused by a general failure of enzyme induction in response to cyclic AMP. The decreased growth rate in older cells result from a general decline in response to several growth factors. However, the decline in 17α-hydroxylase induction did not result from a loss of response of the cells to mitogens, since quiescent cells at a low population doubling level showed stimulation of 17α-hydroxylase mRNA by cholera toxin to levels similar to those in nonquiescent cultures and added mitogens either had no effect on 17α-hydroxylase mRNA levels or decreased them. There was, however, a specific posttranscriptional effect of insulin on 17α-hydroxylase. The loss of 17α-hydroxylase induction is unlikely to result from overgrowth of a minority cell type lacking the ability to induce 17α-hydroxylase, because adrenocortical cell clones that had high levels of 17α-hydroxylase induction gave rise to cells with lower levels of induction on subcloning. Thus, loss of 17α-hydroxylase activity in adrenocortical cellular senescence results from a primary failure of accumulation of 17α-hydroxylase mRNA after incubation with the inducing agent.",
author = "Hornsby, {P. J.} and Hancock, {J. P.} and Vo, {T. P.} and Nason, {L. M.} and Ryan, {R. F.} and McAllister, {J. M.}",
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Loss of expression of a differentiated function gene, steroid 17α-hydroxylase, as adrenocortical cells senesce in culture. / Hornsby, P. J.; Hancock, J. P.; Vo, T. P.; Nason, L. M.; Ryan, R. F.; McAllister, J. M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 84, No. 6, 30.06.1987, p. 1580-1584.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Loss of expression of a differentiated function gene, steroid 17α-hydroxylase, as adrenocortical cells senesce in culture

AU - Hornsby, P. J.

AU - Hancock, J. P.

AU - Vo, T. P.

AU - Nason, L. M.

AU - Ryan, R. F.

AU - McAllister, J. M.

PY - 1987/6/30

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N2 - Senescence in cultured adrenocortical cells involves changes in expression of differentiated functions as well as changes in responses to mitogenic stimulation. Steroid 17α-hydroxylase (steroid 17α-monooxygenase, EC 1.14.99.9) is an adrenal-specific enzyme, the expression of which is dependent on the presence of stimulators of cyclic AMP production, such as cholera toxin. Dot-blot hybridization of RNA from bovine adrenocortical cells that had been incubated with cholera toxin showed a marked decline in 17α-hydroxylase mRNA levels as a function of population doubling level, closely paralleling the decline in induction of 17α-hydroxylase enzyme activity. The lower levels of 17α-hydroxylase induction did not result from a requirement for a longer time period for induction or from a specific defect in response to cholera toxin and were not caused by a general failure of enzyme induction in response to cyclic AMP. The decreased growth rate in older cells result from a general decline in response to several growth factors. However, the decline in 17α-hydroxylase induction did not result from a loss of response of the cells to mitogens, since quiescent cells at a low population doubling level showed stimulation of 17α-hydroxylase mRNA by cholera toxin to levels similar to those in nonquiescent cultures and added mitogens either had no effect on 17α-hydroxylase mRNA levels or decreased them. There was, however, a specific posttranscriptional effect of insulin on 17α-hydroxylase. The loss of 17α-hydroxylase induction is unlikely to result from overgrowth of a minority cell type lacking the ability to induce 17α-hydroxylase, because adrenocortical cell clones that had high levels of 17α-hydroxylase induction gave rise to cells with lower levels of induction on subcloning. Thus, loss of 17α-hydroxylase activity in adrenocortical cellular senescence results from a primary failure of accumulation of 17α-hydroxylase mRNA after incubation with the inducing agent.

AB - Senescence in cultured adrenocortical cells involves changes in expression of differentiated functions as well as changes in responses to mitogenic stimulation. Steroid 17α-hydroxylase (steroid 17α-monooxygenase, EC 1.14.99.9) is an adrenal-specific enzyme, the expression of which is dependent on the presence of stimulators of cyclic AMP production, such as cholera toxin. Dot-blot hybridization of RNA from bovine adrenocortical cells that had been incubated with cholera toxin showed a marked decline in 17α-hydroxylase mRNA levels as a function of population doubling level, closely paralleling the decline in induction of 17α-hydroxylase enzyme activity. The lower levels of 17α-hydroxylase induction did not result from a requirement for a longer time period for induction or from a specific defect in response to cholera toxin and were not caused by a general failure of enzyme induction in response to cyclic AMP. The decreased growth rate in older cells result from a general decline in response to several growth factors. However, the decline in 17α-hydroxylase induction did not result from a loss of response of the cells to mitogens, since quiescent cells at a low population doubling level showed stimulation of 17α-hydroxylase mRNA by cholera toxin to levels similar to those in nonquiescent cultures and added mitogens either had no effect on 17α-hydroxylase mRNA levels or decreased them. There was, however, a specific posttranscriptional effect of insulin on 17α-hydroxylase. The loss of 17α-hydroxylase induction is unlikely to result from overgrowth of a minority cell type lacking the ability to induce 17α-hydroxylase, because adrenocortical cell clones that had high levels of 17α-hydroxylase induction gave rise to cells with lower levels of induction on subcloning. Thus, loss of 17α-hydroxylase activity in adrenocortical cellular senescence results from a primary failure of accumulation of 17α-hydroxylase mRNA after incubation with the inducing agent.

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