Diffusion of [3H] Testosterone from Hypothalamic Microimplants in Castrated Male Gerbils: Correlation with Acute Changes in Plasma LH1

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Abstract
Quantitative aspects of the movement of radiolabeled testosterone from microimplants placed in the basal hypothalamus were studied and the acute effects of these implants on plasma LH [luteinizing hormone] levels were determined in castrated Mongolian gerbils. Movement of [3H]testosterone (*T) from both extruded and nonextruded (i.e., retained in cannula) implants was evaluated at 30 min, 2, 4, 6, 12, 24 h and 1 wk after implant. There was no difference [3H]cholesterol and *T in the distance and amount of diffusion at any time. The amount of label which diffused did not increase within the 1st 24 h, but averated 8 times greater for extruded than for nonextruded implants at any given time. The distance of diffusion was not different at any time for the 2 implant types. The most rapid movement of label beyond the implant was in the first 6 h (up to 400 .mu.m) with no further increase by 24 h. After 1 wk, radioactivity was detectable as far as 1.1 mm beyond the implant site, but only 9.2% of the radioactivity in the brain was present beyond the implant site. Radioactivity was detectable in pituitary tissue in 45% of the pituitaries in the 30 min group, but not in any other group. Significant metabolism of the diffused [3H]testosterone occurred within the hypothalamus. Only 49% of the radioactivity recovered from the chromatogram of hypothalamic tissue samples taken 6 h after implant placement migrated as testosterone. Dihydrotesterone was the major metabolite. Only implants containing testosterone resulted in a decrease in plasma LH concentration below castrate control levels. Within 6 h after placement of implant, LH was decreased 30% and by 24 h, LH was decreased 81%. No difference in LH concentration was observed between groups with extruded and groups with nonextruded implants. The timing and amount of decrease in LH was not different whether radioactivity was or was not detectable in the pituitary at any time. These results suggest that diffusion from site of implant and hormone metabolism should be carefully considered in evaluating effect of hypothalamic implants of steroid hormone. Correlation of testosterone diffusion with changes in plasma LH and possible pituitary mediation of the testosterone effect is discussed.