Serum and CSF concentrations of testosterone and LH related to negative feedback in male rhesus monkeys

Testosterone and LH concentrations were studied in blood and cerebrospinal fluid (CSF) in 8 adult male rhesus monkeys. All males were initially intact and 7 were subsequently castrated and implanted with an ascending series of testosterone capsules. In 4 of the males, serum testosterone levels were significantly higher at 21.00 h than at 09.00 h when the monkeys were intact. Following castration of these 4 males, 4-10 testosterone capsules produced serum concentrations similar to those previously found at 09.00 h; levels equivalent to those at 21.00 h were attained with 12-14 capsules. The proportion of unbound testosterone in serum represented 2% of total serum concentrations, but increased to 4% at high serum concentrations (12-14 capsules). In contrast, the proportion of unbound testosterone in CSF represented 100% of CSF levels. The levels of testosterone in CSF remained at values equal to 2-3% of total serum concentrations throughout the study. The levels of unbound serum testosterone and testosterone levels in the CSF were similar throughout the study in 3 of the 4 monkeys. In the fourth animal, supraphysiological serum testosterone levels occurred with 12 and 14 implants, and, at this time, the level of testosterone in CSF was less than the concentrations of unbound testosterone in serum. Following an intravenous bolus injection of testosterone, the steroid rapidly entered CSF when either 6 or 14 capsules were in place. Although the clearance of testosterone was similar within either compartment during both treatments, the half-life of testosterone in CSF was significantly shorter than in serum at high serum concentrations (14 capsules). Serum and CSF LH levels rose rapidly after castration, reaching maximal levels 8-12 days later with CSF LH levels consistently representing 2-3% of serum concentrations. Post-castration LH concentrations did not change until nocturnal testosterone levels were reached (12-14 capsules), when LH levels were suppressed in both serum and CSF. Subsequent reduction of serum testosterone levels (to 6 capsules) maintained the low LH concentrations. Seemingly, high testosterone concentrations in either serum or CSF, equivalent to nocturnal levels in intact males, were required to initiate LH suppression, but not to maintain it.