Progesterone-associated arginine decline at luteal phase of menstrual cycle and associations with related amino acids and nuclear factor kB activation

PLoS One. 2018 Jul 10;13(7):e0200489. doi: 10.1371/journal.pone.0200489. eCollection 2018.

Abstract

Background/objectives: Given their role in female reproduction, the effects of progesterone on arginine and related amino acids, polyamines and NF-κB p65 activation were studied across the menstrual cycle.

Methods: Arginine, ornithine and citrulline as well as putrescine, spermidine, spermine, and N-acetyl-putrescine were determined in plasma, NF-κB p65 activation in peripheral blood mononuclear cells and progesterone in serum of 28 women at early (T1) and late follicular (T2) and mid (T3) and late (T4) luteal phase.

Results: Arginine and related amino acids declined from T1 and T2 to T3 and T4, while progesterone increased. At T3, arginine, ornithine, and citrulline were inversely related with progesterone. Changes (ΔT3-T2) in arginine, ornithine, and citrulline were inversely related with changes (ΔT3-T2) in progesterone. Ornithine and citrulline were positively related with arginine, as were changes (ΔT3-T2) in ornithine and citrulline with changes (ΔT3-T2) in arginine. At T2, NF-κB p65 activation was positively related with arginine. Polyamines did not change and were not related to progesterone. All results described were significant at P < 0.001.

Conclusions: This study for the first time provides data, at the plasma and PBMC level, supporting a proposed regulatory node of arginine and related amino acids, progesterone and NF-κB p65 at luteal phase of the menstrual cycle, aimed at successful preparation of pregnancy.

Keywords: nuclear factor kappa B; NFkB; NFκB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acids / blood
  • Arginine / blood*
  • Citrulline / metabolism
  • Female
  • Follicular Phase
  • Healthy Volunteers
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Luteal Phase / blood*
  • NF-kappa B p50 Subunit / blood
  • Ornithine / metabolism
  • Progesterone / physiology*
  • Putrescine / metabolism
  • Reference Values
  • Spermidine / metabolism
  • Spermine / metabolism
  • Transcription Factor RelA / blood

Substances

  • Amino Acids
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • RELA protein, human
  • Transcription Factor RelA
  • Citrulline
  • Spermine
  • Progesterone
  • Arginine
  • Ornithine
  • Spermidine
  • Putrescine

Grants and funding

This work was carried out with financial support of the European Union’s 7th Framework Programme FP7 2007-2013 under grant agreement nº 244995 (BIOCLAIMS Project) to Karl-Franzens University, Graz, Austria (BWR), and Medical University, Graz, Austria (JMR) and of the Federal Ministry of Science, Research and Economy of Austria under grant agreement GZ 651.483/0001-II/2/2010 to Karl-Franzens University, Graz, Austria (BWR), and grant agreement GZ 651.484/0001-II/2/2010 to Medical University, Graz, Austria (JMR) for the BIOCLAIMS Project, and of the European Union’s 5th Framework Programme under grant agreement nº QLK1-CT-1999-00830 (VITAGE Project) to Karl-Franzens University, Graz, Austria (BWR), Institut National de la Recherché Agronomique, Clermont-Ferrand, France (ER), and Universitat Rovira I Virgili, Tarragona, Spain (JR), and of the Federal Ministry of Science, Research and Economy of Austria under grant agreement GZ 650.874/1-VI/2/2003 to Karl-Franzens University, Graz, Austria (BWR), for the VITAGE Project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.