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Cis-unsaturated free fatty acids block VIP-mediated GH and PRL secretion by perturbing the cAMP/protein kinase A

F R Pérez1, J P Camiña, C Menéndez

  • 1Department of Medicine, Compostela University School of Medicine, Santiago de Compostela, Spain.

Pituitary
|November 18, 2000
PubMed

Insights

Cis-unsaturated free fatty acids (FFA) inhibit growth hormone and prolactin secretion by disrupting the cAMP/protein kinase A pathway in pituitary cells. These fatty acids interfere with adenylate cyclase and protein kinase A activity, impacting calcium influx.

Area of Science:

  • Endocrinology
  • Cell Signaling
  • Molecular Biology

Background:

  • Cis-unsaturated free fatty acids (FFA) inhibit basal and stimulated growth hormone (GH) secretion by acting directly on somatotroph cells.
  • Evidence suggests FFA's inhibitory action stems from perturbing plasma membrane integral proteins.
  • Previous studies indicate cis-FFA block the inositolphosphates/phospholipase C/Ca2+ (InsPs/PLC/Ca2+) signal transduction pathway.

Purpose of the Study:

  • To investigate the inhibitory mechanisms of cis-FFA on growth hormone (GH) and prolactin (PRL) secretion in pituitary clonal cells.
  • To determine how cis-FFA affect the cAMP-protein kinase A (cAMP/PKA) pathway activated by vasoactive intestinal peptide (VIP) receptor stimulation.
  • To elucidate the specific levels at which cis-FFA interfere with the VIP-triggered signaling cascade.

Main Methods:

  • Sequential analysis of signal transduction events in pituitary clonal cells.
  • Measurement of adenylate cyclase activity.
  • Assessment of protein kinase A activity.
  • Monitoring of VIP-triggered Ca2+ influx.
  • Evaluation of VIP receptor binding and desensitization.

Main Results:

  • Cis-unsaturated FFA were found to reduce adenylate cyclase activity.
  • The activity of protein kinase A (PKA) was perturbed by cis-FFA.
  • VIP-triggered Ca2+ influx was suppressed by cis-unsaturated FFA.
  • Cis-FFA did not affect VIP binding or homologous desensitization of the VIP receptor.

Conclusions:

  • Cis-unsaturated FFA inhibit GH and PRL secretion by interfering with the cAMP/PKA pathway in pituitary clonal cells.
  • The inhibitory effects involve reduced adenylate cyclase activity, perturbed PKA activity, and suppressed Ca2+ influx.
  • These findings highlight specific molecular targets for FFA action within the VIP receptor signaling pathway, distinct from receptor binding itself.

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