title: In young men, a moderate inhibition of testosterone synthesis capacity is only partly compensated by increased activity of the pituitary and the hypothalamus.
abstract: BACKGROUND
  The classical interpretation of the feedback regulation of the male hypothalamo-pituitary-gonadal axis predicts that a partial inhibition of testosterone (T) synthesis will result in a compensatory rise in LH secretion. The question arises as to whether such a compensation is complete or that decreased T synthesis may result in a lower plasma T concentration.
  
  
  OBJECTIVE
  To investigate whether a moderate inhibition of T synthesis capacity will be fully compensated by increased LH secretion. DESIGN, SUBJECTS AND INTERVENTIONS: In nine young healthy men, we partially inhibited T synthesis capacity using ketoconazole (KTZ) 100 mg four times daily. On day -6 (1 week prior to KTZ intake), days 1 and 8 of KTZ administration blood was drawn [07:00 h (t(1)), 10:00 h (t(2)), 13:00 h (t(3))] for evaluation of T, LH, oestradiol (E2), 17-OH-progesterone (17OHP), progesterone (PR) and sex hormone binding globulin (SHBG). On day 8, 5000 IU of hCG were administered to evaluate the maximal T secretion under KTZ.
  
  
  RESULTS
  Administration of KTZ resulted in an acute, moderate but significant decrease of plasma T concentration. On day 8, plasma LH, 17OHP and PR were elevated relative to day -6 and day 1, but mean T was still lower compared to day -6. Mean E2 and SHBG were only slightly affected by KTZ. After stimulation by hCG, plasma T was restored to its baseline level.
  
  
  CONCLUSIONS
  These results argue against the assumption that a moderate decline in T synthesis capacity will be compensated completely by increased LH secretion.
authors.affiliation: Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jorn
authors.initials: J
authors.lastname: Woerdeman
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Kaufman
authors.forename: Willem
authors.initials: W
authors.lastname: de Ronde
mesh_terms: D000328:Adult; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood; D025461:Feedback, Physiological / Q000187:drug effects; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007654:Ketoconazole / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D010907:Pituitary Hormones / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D055815:Young Adult
chemical_list: D000726:Androgen Antagonists; D010907:Pituitary Hormones; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D013254:Steroid 17-alpha-Hydroxylase; D007654:Ketoconazole