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Janine L. Brown and Prabir K. Chakraborty

Abstract. A previous study showed that clomiphene citrate (clomiphene) reduced serum and pituitary gonadotropins and impaired testis growth and steroidogenesis in 10-day-old rats treated for up to two weeks. The present study was conducted to assess the effect of prepubertal clomiphene treatment on postpubertal pituitary-testicular function. Rats were implanted with pellets that released 0, 0.05, 0.5 or 5.0 mg clomiphene ·kg−1·day−1 between 10–31 days of age and were killed at 90 days of age. Testis and prostate weights in treated rats were reduced (P< 0.05), whereas serum LH, FSH and testosterone, and pituitary gonadotropin and GnRH receptor concentrations had recovered to levels observed in control rats. Testicular FSH receptor concentrations were not altered; however, FSH receptor content was decreased (P< 0.05) in clomiphene-treated rats proportional to the reduction in testicular weight. In contrast, testicular LH and GnRH receptor concentrations were increased (P< 0.05) in treated animals, resulting in similar receptor contents. Daily sperm production per gram of parenchyma was unaffected, while daily sperm production per testis was decreased in treated rats (P< 0.05). These data show early postnatal treatment with clomiphene does not permanently impair pituitary function. Despite reduced testicular mass, normal serum testosterone concentrations and testis LH receptor content of treated rats suggest recovered Leydig cell function. The decreased content of testicular FSH receptors and reduced sperm production suggest seminiferous tubule function was compromised in the adult rat.

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Janine L. Brown and Prabir K. Chakraborty

Abstract. Clomiphene citrate (clomiphene) inhibits reproduction in male rats; however, stimulatory effects have been reported at low doses. Male rats were implanted at 60 (adult), 35 (peripubertal) or 10 (prepubertal) days of age with pellets that delivered 0,0.05, 0.5 or 5.0 mg clomiphene · kg−1 · day−1 and were sacrificed after 7 or 14 days of treatment. Testis weight was unaffected by clomiphene in adult and peripubertal rats, but was reduced by all doses in prepubertal rats. Seminal vesicle and prostate gland weights were decreased to varying degrees by clomiphene in all animals, except seminal vesicle weight in peripubertal rats. Serum LH and testosterone were decreased by most doses in all age groups, whereas pituitary LH was decreased in prepubertal rats only. Pituitary GnRH and testicular LH receptor concentrations were reduced in all treated animals. Serum and pituitary FSH were decreased in pre- and peripubertal rats, whereas testicular FSH receptor concentrations were unaffected by treatment. In summary, 1) reproductive function was compromised by clomiphene and many responses were age-dependent, 2) reductions in gonadotropins suggest that clomiphene decreased their synthesis and/or release, and 3) decreased serum LH and testicular LH receptor concentrations were coupled to reduced testosterone secretion.