title: Combined inhibition of types I and II 5 alpha-reductase selectively augments the basal (nonpulsatile) mode of testosterone secretion in young men.
abstract: BACKGROUND
  Testosterone (Te) is metabolized in the hypothalamus and pituitary gland, where untransformed steroid and activated products participate in feedback regulation of GnRH and LH secretion. Genetic inactivation of 5 alpha-reductase type I remains undescribed clinically, whereas deficiency of the type II isoenzyme elevates both LH and Te concentrations.
  
  
  OBJECTIVE
  The aim of this study was to test the combined feedback contribution of 5 alpha-reduced steroids. SETTING/DESIGN/INTERVENTION: In a university setting, nine young men received placebo and a dual (type I/type II) 5 alpha-reductase inhibitor, dutasteride.
  LH and Te dynamics were assessed by: 1) 10-min blood sampling for 26 h; 2) GnRH stimulation (100 ng/kg iv); 3) discrete peak detection; 4) deconvolution analysis; 5) cosinor analyses of 24-h rhythmicity; and 6) pattern regularity.
  
  
  RESULTS
  Compared with placebo, dutasteride lowered 5 alpha-dihydro Te concentrations by 80% (P = 0.009), but did not alter any measure of LH dynamics. Conversely, dutasteride augmented: 1) total, bioavailable and free Te concentrations (0.002 < P < 0.032) without changing estradiol or SHBG concentrations; 2) nadir Te concentrations (P = 0.025); and 3) basal (P = 0.013) and thereby total (basal plus pulsatile) (P = 0.003) Te secretion.
  
  
  CONCLUSIONS
  Combined antagonism of types I and II 5 alpha-reductase preferentially drives nonpulsatile Te secretion in healthy men. The concomitant stability of LH outflow could indicate that intragonadal 5 alpha-reduced androgens repress basal Leydig-cell steroidogenesis.
authors.affiliation: Endocrine Service, Research and Development, Salem Veterans Affairs Medical Center, Virginia 24153, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Iranmanesh
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D000328:Adult; D042944:Cholestenone 5 alpha-Reductase / Q000037:antagonists & inhibitors* / Q000145:classification; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D042944:Cholestenone 5 alpha-Reductase