Differential effect of difluoromethylornithine on the increases in plasma concentrations of reproductive hormones on the afternoon of pro-oestrus in the rat

Abstract

In our colony of female rats (220-320 g body weight) undergoing regular 4-day oestrous cycles there were significant, marked rises in concentrations of LH, FSH and prolactin between 09.00 and 19.00 h on pro-oestrus. The i.p. injection of difluoromethylornithine (DFMO; 40-400 mg/kg), a specific inhibitor of the activity of ornithine decarboxylase, at 15.00 h on pro-oestrus had a differential effect on the rise in plasma concentrations of the various hormones thereafter. The drug produced a significant, partial, dose-related suppression of the rise in plasma concentrations of LH and prolactin, but had no significant effect on the rise in FSH. For time-course studies, 120 mg DFMO/kg were injected at 13.00, 15.00 or 17.00 h and groups of animals killed at 19.00 h. Only the injection at 15.00 h was effective in causing a significant reduction in plasma concentrations of LH and prolactin at 19.00 h. Pituitary content of the hormones was found to be unaffected by the administration of DFMO at the times and doses tested. These results suggest that DFMO has a selective inhibitory effect on enhanced LH and prolactin secretion on the afternoon of pro-oestrus in the rat, whilst not affecting FSH release. There seems to be a limited time (after 13.00 but before 17.00 h) during which its administration is effective.

Effects of Polyamines on the Release of Gonadotropin-Releasing Hormone and Gonadotropins in Developing Female Rats

“…In addition, in a pioneer work, White et at. (10) showed that polyamines were related to gonadotropin release and this was later confirmed bY other authors (11,12). Polyamines, specifically putrescine, were also related to -y-aminobutyric acid (GAB A) synthesiSi a neurotransmitter critically involved in the regulation 0 gonadotropin secretion (13).…”

Regulation of the hypothalamic GnRH–GnIH system by putrescine in adult female rats and GT1‐7 neuronal cell line

“…α‐Difluoromethylornithine (DFMO), is a potent irreversible inhibitor of ODC1 has shown to inhibit ovarian growth, antral follicle formation, and the onset of puberty (Bastida et al, 2005). Studies have also shown that DFMO treatment has decreased luteinizing hormone (LH), progesterone, and prolactin levels and number of ovulated oocytes in female adult rodents (Nicholson & Wynne‐Jones, 1989; Nicholson, Aslam, Chuang, Gillham, & Jones, 1988). A study showed that the metabolism and requirement of polyamines in cancer is altered (Nowotarski, Woster, & Casero, 2013), and recently, DFMO maintenance therapy for neuroblastoma in remission has been shown to be safe (Sholler et al, 2018).…”