NOVEL BIOMARKERS OF ANDROGEN DEFICIENCY FROM SEMINAL PLASMA PROFILING USING HIGH-RESOLUTION MASS SPECTROMETRY.

CONTEXT: The seminal plasma is made out of secretions from the testis, the epididymis and the male accessory glands, that are dependent upon the presence of androgenic stimuli. OBJECTIVE: The objective of this study was to identify new seminal biomarkers for secundary male hypogonadism using proteomic profiling. DESIGN: 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 bioformatic tools. SETTING: The study was performed at a clinical research center. SUBJECTS: Twenty male patients, aged 25-55 yr, affected by secundary hypogonadic were studied. Ten patients were re-evaluated after 6 months of testosterone replacement therapy(TRT). Ten normogonadic men were enrolled as control group.INTERVENTIONS: none MAIN OUTCOME MEASURES: 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 (AR). RESULTS: A lower number of proteins was identified in hypogonadic patients compared with normogonadal men. Among the 61 proteins identified in normogonadal men, proteins 44 were absent in hypogonadic patients. 14 out 33 absent proteins were identified in seminal samples after 6 months of TRT. Functional annotation analysis revealed that binding and 46 enzymatic activities are mainly deficient in male hypogonadism. 7 out of 14 differentially expressed proteins can fall into one large protein-protein interaction network, which directly 48 involves the AR.