Endocrinological assessment of toxic effects on the male reproductive system in rats treated with 5-fluorouracil for 2 or 4 weeks.
Endocrinological assessment of male reproductive toxicity was carried out in SD-Slc male rats treated with 5-FU (0, 20, 30 mg/kg/day) orally for 2-week or 4-week term. Serum hormone levels including GnRH, FSH, LH, prolactin, total and free testosterone, inhibin B, pro-alpha C, and activin A were determined as well as histopathological examination of the reproductive organs. The 5-FU treated groups showed histopathological changes in the testis such as degeneration of seminiferous epithelium. An obvious decrease in serum testosterone level was observed with a reduced organ weight of the seminal vesicle and prostate. However, no significant changes were noted in serum LH or FSH levels, nor in the morphological examination of the Leydig cells. Decreased serum levels were noted in activin A and prolactin. An increased serum level was noted in GnRH and pro-alpha C whose synthesis is regulated by FSH. Serum inhibin B levels showed a tendency toward decreasing with morphological change (vacuolation) in Sertoli cells. These results indicated that male reproductive toxicity induced by 5-FU would be augmented by decreased serum prolactin and testosterone levels as well as a decreased function of Sertoli cell, in addition to the direct cytotoxic effects on germ cells. It is suggested that these endocrinological changes related to male reproductive toxicities can be detected even in the 2-week-treated study.
Takizawa
Setsuko
S
Department of Preclinical Science, Nippon Roche K. K., Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
Horii
Ikuo
I
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D005837:Genitalia, Male / Q000187:drug effects* / Q000473:pathology; D012739:Gonadal Steroid Hormones / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000473:pathology
D000963:Antimetabolites; D012739:Gonadal Steroid Hormones; D005472:Fluorouracil