Neonatal treatment of male rats with a gonadotropin-releasing hormone antagonist results in altered function of the pituitary-testicular axis in adult age

In most mammals, pituitary-testicular hormone secretion is very active during the perinatal period, but the physiological significance of this function for later pituitary-gonadal interactions and sexual maturation is largely unknown. Short-term neonatal treatment with gonadotropin-releasing hormone (GnRH) antagonist results in delayed sexual maturation and infertility in male rats. We have now extended our earlier findings and studied in more detail the pituitary-gonadal function in adult rats after such neonatal treatment. In this study, the pituitary-testicular activity of newborn male rats was temporarily blocked by treatment with a GnRH antagonist analogue (N-Ac-4-Cl-D-Phe1, 4-Cl-D-Phe2, D-Trp3, D-Phe6, des-Gly10-GnRH-D-alanylamide; Organon 30039; 2 mg/kg s.c. twice daily) on Days 1-5 of life. Timing of puberty was slightly delayed in the treated rats (average: 2 days, p less than 0.05), as determined by the age of the balano-preputial separation. In adult rats (90-110 days), only 3 of the 17 rats treated neonatally with GnRH antagonist were fertile (14 of 17 controls, p less than 0.01), despite normal circulating androgen levels. Pituitary and serum follicle-stimulating hormone (FSH) levels were slightly but consistently elevated (20-30%; p less than 0.05) in antagonist-treated animals, whereas luteinizing hormone (LH) levels (both immunoreactive and bioactive) were unaffected. The pituitary contents of GnRH receptors were increased in antagonist-treated animals 85 +/- 6.6 (mean +/- SEM, n = 19) vs. 58 +/- 4.1 fmol/gland in controls (n = 20; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)