Temporal Effects of Testosterone-Estradiol Polydimethylsiloxane Subdermal Implants on Pituitary, Leydig Cell, and Germinal Epithelium Function and Daily Serum Testosterone Rhythm in Male Rats1

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Abstract
Testosterone and estradiol, administered by polydimethylsiloxane (PDS) Silastic implants, act synergistically to inhibit spermatogenesis. In previous experiments, we examined the effect of testosterone plus estradiol implants on pituitary and testicular function at a single time interval after implantation (usually 3 months). In the present study, we killed rats at 4 h intervals (0400, 0800, 1200, 1600, 2000, and 2400 h) on Days 0, 2, 9, 16, 29, and 57 after implanting testosterone-estradiol PDS capsules. We measured serum concentrations of luteinizing hormone, testosterone, and estradiol; testosterone production by in vitro perfused testes; daily sperm production; and body, testis, epididymal, seminal vesicle, and ventral prostate weights. Luteinizing hormone was not detectable in the serum 2 days after implanting PDS capsules and remained suppressed until the end of the study. Testosterone secretion declined to low levels 9 days postimplantation and remained suppressed until the end of the study. Sperm production was inhibited completely by 57 days postimplantation. Serum testosterone and estradiol concentrations increased immediately after implantation of the PDS capsules but returned towards control values as Leydig cell testosterone production declined. Control rats showed a diurnal rhythm in serum testosterone concentration which had a frequency of 2 cycles per day and an amplitude of 2.2 ng/ml. The testosterone plus estradiol PDS subdermal implants altered the diurnal rhythm in serum testosterone concentration prior to 29 days of treatment. After 29 days of treatment, the diurnal rhythm in serum testosterone concentration disappeared. These complex changes in the diurnal rhythm of serum testosterone concentration during the first 29 days were interpreted to mean that both testicular testosterone production and testosterone metabolism were responsible for maintaining the rhythm in control rats.