ALPHA-DIFLUOROMETHYLORNITHINE MODIFIES FSH-SECRETION AND PUBERTY ONSET IN THE FEMALE RAT

FSH secretion is high in immature female rats from Postnatal Day 5 to 18 and decreases thereafter. This is a relatively steroid-independent event of cerebral origin and of importance for puberty onset. Polyamin es, a group of ubiquitous amines, play an essential role in tissue gro wth and differentiation, body weight increment, brain organization, an d molecular mechanisms of hormonal action. Polyamine levels as well as the activity of ornithine decarboxylase, the limiting enzyme in polya mines biosynthesis, are highest during development. Inhibition of thei r synthesis during this period by alpha-difluoromethylornithine (DFMO) , a specific and irreversible inhibitor of ornithine decarboxylase, Im pairs normal brain development. The present study tested the hypothesi s that polyamines play a role during brain organization of reproductio n. DFMO was administered following different schedules in female newbo rn rats, and the effect on pituitary secretion, puberty onset, and fer tility was evaluated. In three groups (daily injections from Day 1 to 9, or from Day 1 to 6, or injections on alternate days from Day 1 to 9 ), a delay in vaginal opening and first estrous was observed. When vag inal opening was plotted against body weight, it was evident that in g roups daily injected with DFMO vaginal opening occurred at a lower bod y weight. In the group treated on alternate days, a delay occurred but at a higher body weight than in controls. In this group, serum FSH le vels on Day 10 and 20, but not on Day 30, were higher in DFMO rats. In the group treated from Day 1 to 6 daily, DFMO increased serum FSH on Postnatal Day 20. After vaginal opening, estrous cyclicity in control and DFMO injected rats was similar. There was no significant effect of treatment on fertility and litter weight or number of offspring at bi rth.It is concluded that DFMO, an inhibitor of ornithine decarboxylase , administered during the first week of life in female rats Is followe d by prolonged high FSH serum levels and delayed puberty, but once pub erty occurs, fertility is normal.