Short-Term Effect of Induced Alterations in Testosterone Levels on Fasting Plasma Amino Acid Levels in Healthy Young Men

Abstract

Long term effect of testosterone (T) deficiency impairs metabolism and is associated with muscle degradation and metabolic disease. The association seems to have a bidirectional nature and is not well understood. The present study aims to investigate the early and unidirectional metabolic effect of induced T changes by measuring fasting amino acid (AA) levels in a human model, in which short-term T alterations were induced. We designed a human model of 30 healthy young males with pharmacologically induced T changes, which resulted in three time points for blood collection: (A) baseline, (B) low T (3 weeks post administration of gonadotropin releasing hormone antagonist) and (C) restored T (2 weeks after injection of T undecanoate). The influence of T on AAs was analyzed by spectrophotometry on plasma samples. Levels of 9 out of 23 AAs, of which 7 were essential AAs, were significantly increased at low T and are restored upon T supplementation. Levels of tyrosine and phenylalanine were most strongly associated to T changes. Short-term effect of T changes suggests an increased protein breakdown that is restored upon T supplementation. Fasting AA levels are able to monitor the early metabolic changes induced by the T fluctuations.

Keywords: gluconeogenesis; protein breakdown; testosterone.

Figure 1

An overview of the pharmacologically induced testosterone (T) states with three time points: (A) baseline (B) Low T (due to chemical castration) and (C) Restored T. Blood collected from each time point was aliquoted and stored in −80 °C prior to analysis within a cycle time of two hours.

Figure 2

Box-plots distribution at (A) baseline, (B) low T and (C) restored T for nine AAs that have at least significant change in B-A and C-B (FDR < 0.05). The AAs are negatively influenced by T: aspargine (Asn), histidine (His), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), tryptophan (Trp), tyrosine (Tyr), and valine (Val), meaning that they are increased with low T and restored upon T supplementation. * p < 0.05, ** p < 0.01, *** p < 0.001.