Transcriptional and posttranscriptional regulation of intraovarian insulin-like growth factor-binding proteins by interleukin-1β (IL-1β): Evidence for IL-1β as an antiatretic principal

Diran Chamoun, Marcos D. DeMoura, Eliahu Levitas, Carol E. Resnick, Sharron E. Gargosky, Ronald (Ron) Rosenfeld, Tomoko Matsumoto, Eli Y. Adashi

Research output: Contribution to journalArticle

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Abstract

Intraovarian interleukin-1 (IL-1), a putative intermediary in the ovulatory cascade, has recently been implicated as an antiatretic agent. Given the reported antigonadotropic and thus atretogenic potential of granulosa cell-derived insulin-like growth factor-binding proteins (IG-FBPs), we evaluated the ability of IL-1β to regulate ovarian IGFBP-4 and -5, the IGFBP species elaborated by the rat granulosa cell. Treatment of whole ovarian dispersates of immature rat origin with increasing concentrations of IL-1β for 96 h resulted in substantial and significant time-dependent inhibition of IGFBP-4 and IGFBP-5 transcripts compared with that in untreated controls. The IL-1 effect proved relatively specific in that no significant alterations in IGFBP transcripts were observed in the presence of select ovarian agonists, including transforming growth factor-α, tumor necrosis factor-α, endothelin-1, hepatocyte growth factor, keratinocyte growth factor, or basic fibroblast growth factor. The inhibitory effect of IL-1β on ovarian IGFBP-4 and -5 expression was almost completely reversed in the presence of IL-1 receptor antagonist, suggesting mediation via a specific IL-1 receptor. The addition of actinomycin D to IL-1β-pretreated whole ovarian dispersates produced a pattern of (IGFBP-4 and -5) messenger RNA decay indistinguishable from that noted for the untreated control group. Medium conditioned by IL-1β-treated (but not untreated) whole ovarian dispersates displayed a marked diminution in the relative content of the IG-FBP-4 and IGFBP-5 proteins (24- and 28- to 29-kDa proteins, respectively). Medium conditioned by IL-1β-treated (but not untreated) whole ovarian dispersates proteolyzed [125I]IGFBP-5 (but not IGFBP-4) into fragments with apparent molecular masses of 18 and 14 kDa, respectively. In conclusion, our present observations demonstrate the ability of IL-1 to 1) inhibit the steady state levels of transcripts corresponding to IGFBP-4 and -5 in a time-dependent, relatively specific, and receptor-mediated fashion; 2) suppress the accumulation of the corresponding IGFBP proteins; and 3) stimulate the activity of the IGFBP-5-directed (but not IGFBP-4) endopeptidase, a posttranscriptional phenomenon. Our findings also suggest, by inference, that the IL-1β-mediated inhibition of IGFBP-4 and -5 transcripts is due in part to a decrease in the rate of transcription of the corresponding genes and not to a change in the stability of the relevant messenger RNAs. Consequently, the ability of IL-1 to influence ovarian IGFBP economy appears multifaceted, comprising both transcriptional and posttranscriptional effects. To the extent that IGFBP-4 and -5 constitute atretogenic agents, our present findings support the view that IL-1β may play an antiatretic role in the context of ovarian physiology.

Original languageEnglish (US)
Pages (from-to)3488-3495
Number of pages8
JournalEndocrinology
Volume140
Issue number8
StatePublished - 1999

Fingerprint

Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor Binding Protein 4
Interleukin-1
Insulin-Like Growth Factor Binding Proteins
Interleukin-1 Receptors
Granulosa Cells
Conditioned Culture Medium
Fibroblast Growth Factor 7
Endopeptidases
Messenger RNA
Proteins
Hepatocyte Growth Factor
RNA Stability
Transforming Growth Factors
Dactinomycin
Endothelin-1
Fibroblast Growth Factor 2

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Chamoun, D., DeMoura, M. D., Levitas, E., Resnick, C. E., Gargosky, S. E., Rosenfeld, R. R., ... Adashi, E. Y. (1999). Transcriptional and posttranscriptional regulation of intraovarian insulin-like growth factor-binding proteins by interleukin-1β (IL-1β): Evidence for IL-1β as an antiatretic principal. Endocrinology, 140(8), 3488-3495.

Transcriptional and posttranscriptional regulation of intraovarian insulin-like growth factor-binding proteins by interleukin-1β (IL-1β) : Evidence for IL-1β as an antiatretic principal. / Chamoun, Diran; DeMoura, Marcos D.; Levitas, Eliahu; Resnick, Carol E.; Gargosky, Sharron E.; Rosenfeld, Ronald (Ron); Matsumoto, Tomoko; Adashi, Eli Y.

In: Endocrinology, Vol. 140, No. 8, 1999, p. 3488-3495.

Research output: Contribution to journalArticle

Chamoun, D, DeMoura, MD, Levitas, E, Resnick, CE, Gargosky, SE, Rosenfeld, RR, Matsumoto, T & Adashi, EY 1999, 'Transcriptional and posttranscriptional regulation of intraovarian insulin-like growth factor-binding proteins by interleukin-1β (IL-1β): Evidence for IL-1β as an antiatretic principal', Endocrinology, vol. 140, no. 8, pp. 3488-3495.
Chamoun, Diran ; DeMoura, Marcos D. ; Levitas, Eliahu ; Resnick, Carol E. ; Gargosky, Sharron E. ; Rosenfeld, Ronald (Ron) ; Matsumoto, Tomoko ; Adashi, Eli Y. / Transcriptional and posttranscriptional regulation of intraovarian insulin-like growth factor-binding proteins by interleukin-1β (IL-1β) : Evidence for IL-1β as an antiatretic principal. In: Endocrinology. 1999 ; Vol. 140, No. 8. pp. 3488-3495.
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AU - DeMoura, Marcos D.

AU - Levitas, Eliahu

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