title: Novel biomarkers of androgen deficiency from seminal plasma profiling using high-resolution mass spectrometry.
abstract: BACKGROUND
  The seminal plasma is made of secretions from the testis, the epididymis, and the male accessory glands, which are dependent on the presence of androgenic stimuli.
  
  
  OBJECTIVE
  The objective of this study was to identify new seminal biomarkers for secundary male hypogonadism using proteomic profiling.
  
  
  METHODS
  Seminal plasma samples from patients affected by secundary hypogonadism and normogonadal controls were analyzed by an LTQ Orbitrap XL hybrid mass spectrometer and data were evaluated using bioinformatic tools.
  
  
  METHODS
  The study was performed at a clinical research center.
  
  
  METHODS
  Twenty male patients, aged 25-55 years, affected by secundary hypogonadic were studied. Ten patients were reevaluated after 6 months of T replacement therapy (TRT). Ten normogonadic men were enrolled as a control group.
  
  
  METHODS
  There were no interventions.
  
  
  METHODS
  The list of absent proteins in the samples of hypogonadic patients and identified after TRT was studied. Bioinformatic tools were used to functionally annotate the panel of androgen-dependent proteins. The interaction network of the differentially expressed proteins was built in silico, including the androgen receptor.
  
  
  RESULTS
  A lower number of proteins was identified in hypogonadic patients compared with normogonadal men. Among the 61 proteins identified in normogonadal men, 33 proteins were absent in hypogonadic patients. Fourteen of 33 absent proteins were identified in seminal samples after 6 months of TRT. Functional annotation analysis revealed that binding and enzymatic activities are mainly deficient in male hypogonadism. Seven of 14 differentially expressed proteins can fall into one large protein-protein interaction network, which directly involves the androgen receptor.
  
  
  CONCLUSIONS
  A high resolution mass spectrometry-based proteomic approach was first used to describe the alterations of seminal seminal proteome in secundary male hypogonadism. These proteins represent putative physiological in vivo targets for androgen deficiency.
authors.affiliation: International Scientific Institute (D.M., R.M.), "Paolo VI", Division of Endocrinology and Metabolic Diseases (G.G., A.G., L.D.M., A.P.), and Institute of Biochemistry and Clinical Biochemistry (F.V., M.C.), Università Cattolica del Sacro Cuore, 00168 Rome, Italy; and Department of Life and Environmental Sciences (I.M.), University of Cagliari, 09124 Cagliari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Milardi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grande
authors.forename: Federica
authors.initials: F
authors.lastname: Vincenzoni
authors.forename: Antonella
authors.initials: A
authors.lastname: Giampietro
authors.forename: Irene
authors.initials: I
authors.lastname: Messana
authors.forename: Massimo
authors.initials: M
authors.lastname: Castagnola
authors.forename: Riccardo
authors.initials: R
authors.lastname: Marana
authors.forename: Laura
authors.initials: L
authors.lastname: De Marinis
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
mesh_terms: D000328:Adult; D000728:Androgens / Q000172:deficiency*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D016022:Case-Control Studies; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D012661:Semen / Q000737:chemistry / Q000378:metabolism; D029589:Seminal Plasma Proteins / Q000032:analysis / Q000378:metabolism*; D013739:Testosterone / Q000627:therapeutic use
chemical_list: D000728:Androgens; D015415:Biomarkers; D029589:Seminal Plasma Proteins; D013739:Testosterone