In young men, a moderate inhibition of testosterone synthesis capacity is only partly compensated by increased activity of the pituitary and the hypothalamus.
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.
Woerdeman
Jorn
J
Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.
Kaufman
Jean-Marc
JM
de Ronde
Willem
W
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
D000726:Androgen Antagonists; D010907:Pituitary Hormones; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D013254:Steroid 17-alpha-Hydroxylase; D007654:Ketoconazole