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We have previously shown that suppression of gonadotropins and spermatogenesis can be produced in rats by immunization against gonadotropin releasing hormone (GnRH). Administration of testosterone (T) alone is effective in restoring complete spermatogenesis in these rats, although it is not effective in doing so in chronically treated hypophysectomized rats. This suggests that a pituitary factor(s) other than luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is required to restore normal spermatogenesis. The studies described herein test the hypothesis that prolactin (PRL) is the additional requirement for complete restoration of spermatogenesis. Twenty rats were immunized against GnRH, and four groups of five each received either 1) 24-cm T-filled Silastic implant (TSl), 2) TSl plus bromocriptine pellet (B), 3) B plus empty Silastic implant (Sl), or 4) Sl alone. Five nonimmunized rats received Sl alone and served as controls. All rats were sacrificed 2 months after treatment. GnRH immunization and B administration suppressed gonadotropins and PRL levels, respectively, and advanced spermatids were not detectable in these rats. Testis weight was suppressed to about 19% of controls. The number of advanced spermatids in control rats was 220 +/- 23 x 10(6). TSl administration restored advanced spermatids to numbers comparable to controls in GnRH-immunized rats whether the rat received B (191 +/- 17 x 106) or not (217 +/- 18 x 10(6)). Additionally, we determined mRNA levels for PRL and FSH beta subunit (FSH beta) in the pituitary by Northern blot and densitometric scanning. The mRNA levels of PRL mirrored serum PRL levels, and the same was true for FSH beta subunits and serum FSH levels. These data show that suppression of PRL has no effect on the ability of T to restore complete spermatogenesis in GnRH-immunized rats. This observation mitigates against the hypothesis that PRL is the pituitary factor required to allow complete restoration of spermatogenesis to occur.

The present study examines whether the antifertility effects of pyrimethamine (PYR), an inhibitor of dihydrofolate reductase, are mediated by a reduction in intratesticular testosterone (T) concentrations or whether PYR exerts its effect by a cytotoxic insult to spermatogenic cells that is independent of intratesticular testosterone. Adult male rats were treated daily with 100 mg/kg (n = 16) or 400 mg/kg (n = 16) of PYR in honey for 8 weeks. Control rats (n = 16) received honey without PYR. Eight weeks after treatment, five rats from each PYR-treated group and five control rats were mated with normal cycling female rats, and fertility was assessed. These rats were euthanized after the fertility trial; testis weight, testicular sperm, and epididymal sperm counts were determined, and serum levels of T, LH, FSH, and seminiferous tubule fluid T (STF-T) concentrations were measured by RIA. Testes from three rats per group were perfusion-fixed for histological evaluation. PYR was discontinued in the remaining rats for 8 weeks and similar parameters were evaluated after 8 weeks of recovery. PYR (100 mg/kg/day) treatment for 8 weeks did not have any effects on organ weights, testicular and epididymal sperm counts, and hormone levels when compared to controls. In contrast, PYR (400 mg/kg/day) treatment significantly reduced testis and epididymis weights, testicular and epididymal sperm counts, and fertility. Despite these effects, serum T, LH, FSH, and STF-T concentrations were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)