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ABSTRACT
The activity of ornithine decarboxylase (ODC) in the rat anterior pituitary gland varies during the oestrous cycle, with a rise in activity seen at pro-oestrus. This enzyme, which is rate-limiting for the synthesis of the polyamines, can be specifically and irreversibly blocked by α-difluoromethylornithine (DFMO). A previous study showed that when this drug was administered to rats in vivo on the afternoon of pro-oestrus, it suppressed the normal surge in plasma prolactin levels that occurred later that day. The effect of DFMO was associated with reduced levels of putrescine in the anterior pituitary gland, suggesting that ODC activity in the lactotroph might be involved in the prolactin surge. We have examined the effects of DFMO on the secretion of prolactin from anterior pituitary cells, isolated either from male rats or from females at different stages of the oestrous cycle. The drug was found to reduce prolactin secretion stimulated by thyrotrophin-releasing hormone (TRH), but only in cells isolated from pro-oestrous animals and only for 2 days after cell isolation. Basal secretion was unaffected by DFMO. The results imply that ODC is important for TRH-stimulated prolactin secretion at pro-oestrus, and it is specific for pro-oestrus. The prolactin surge could therefore be influenced by this ODC-dependent effect of TRH. The pro-oestrous-specific response to TRH may be a consequence of the increased ODC activity seen at this time. Alternatively, the increased ODC activity could be a consequence of coupling to TRH receptors, which are known to increase in number at pro-oestrus.
Journal of Endocrinology (1993) 137, 133–139
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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 prooestrus 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.
Journal of Endocrinology (1989) 121, 495–499