Sexual maturation of male rats treated postnatally with a gonadotrophin-releasing hormone antagonist.

Postnatal secretion of gonadotrophin by male rats was inhibited by a potent gonadotrophin-releasing hormone (GnRH) antagonist analogue (N-Ac-4-Cl-D-Phe1,4-Cl-D-Phe2,D-Trp3,D-Phe6,des-Gly10-GnRH-D-al anylamide; Org 30039; 2 mg/kg s.c. twice daily) on days 1-5, 6-10, 11-15 or 16-20 of life. The onset of puberty was determined by monitoring the separation of the preputium from the glans penis, i.e. balano-preputial separation (BPS). Rats treated on days 1-5 matured normally, whereas all treatments between days 6 and 20 delayed BPS (P less than 0.01). In adult rats (between 110 and 160 days of age), testis weights were reduced by 21-35% (P less than 0.01) in groups treated between days 1 and 15, although weights of the accessory sex glands were normal. Testicular FSH receptors were decreased by 31-47% (P less than 0.01) in all treatment groups, whereas the LH receptor content was decreased only in rats treated between days 1 and 5 (18%; P less than 0.05) and prolactin receptor content decreased only in rats treated up to day 10 (31-33%; P less than 0.01). Concentrations of serum testosterone, LH and FSH, and pituitary contents of LH and FSH were unaffected by neonatal treatment with Org 30039. Animals treated with Org 30039 had reduced fertility which was most pronounced (88%; P less than 0.01) in rats treated between days 1 and 5. However, motile sperm were detectable in the cauda epididymis of the infertile rats.(ABSTRACT TRUNCATED AT 250 WORDS)