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

Abstract

ABSTRACT 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-alanylamide; 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. balanopreputial separation (BPS). Rats treated on days 1–5 matured normally, whereas all treatments between days 6 and 20 delayed BPS (P < 0·01). In adult rats (between 110 and 160 days of age), testis weights were reduced by 21–35% (P < 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 < 0·01) in all treatment groups, whereas the LH receptor content was decreased only in rats treated between days 1 and 5 (18%; P < 0·05) and prolactin receptor content decreased only in rats treated up to day 10 (31–33%; P < 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 < 0·01) in rats treated between days 1 and 5. However, motile sperm were detectable in the cauda epididymis of the infertile rats. In conclusion, postnatal gonadotrophin deprivation induced with a GnRH antagonist for different 5-day periods during the first 15 days of life delayed puberty, reduced adult testis weight and impaired fertility. Some effects of the antagonist were largely independent of the timing of gonadotrophin suppression. Other effects, including suppression of testicular LH and prolactin receptors and the delay in the onset of puberty, were found only in the younger and older treatment groups respectively. These findings emphasize the importance of neonatal hypothalamic-pituitary-gonadal function for subsequent sexual maturation. J. Endocr. (1988) 116, 241–246