Relation between luteinizing hormone and prolactin pulses in ovariectomized rats with or without dopamine inhibition

GnRH and GnRH-associated peptide (GAP) have been shown to be cosecreted as spontaneous pulses in hypophysial portal blood. In addition, GAP has been proposed as a physiological inhibitor of PRL secretion. The present investigation was performed to determine whether GAP might play a role in the moment to moment regulation of PRL release in the ovariectomized rat. We anticipated that an inverse relation might exist between PRL and LH pulses if GAP is a physiological regulator of PRL and is coreleased with GnRH. Serial blood samples were collected at 6-min intervals over 4 h from ovariectomized rats bearing chronic jugular catheters and were analyzed for plasma concentrations of PRL and LH by RIA. Release patterns were assessed using a pulse detection algorithm. Some animals were pretreated 30 min before blood sampling with domperidone (a dopamine antagonist that does not cross the blood-brain barrier) to unmask PRL inhibitory responses to GAP that might not otherwise be observable in the presence of normal dopamine inhibition.PRL secretory patterns were pulsatile but highly irregular, in contrast to the regular rhythmic patterns of circulating LH. Domperidone treatment significantly increased the number of PRL pulses, PRL pulse amplitudes, and mean PRL concentrations compared to those in vehicle-injected controls. LH pulses after domperidone administration were more frequent, resulting in slightly higher mean LH concentrations. In both vehicle- and domperidone-injected rats, 60†80% of PRL pulses were concordant with LH pulses (concordance defined as PRL and LH peaks occurring within one sample of each other). Assuming that GAP is cosecreted with GnRH, these data fail to support an acute physiological role for GAP during undisturbed PRL release in the ovariectomized rat because the expected relation between PRL and LH pulses in the event of such a role was not observed.To test a role for GAP more directly, domperidone-treated rats were injected with a rabbit anti-GAP serum during serial blood collection. No increase in PRL release was elicited by this treatment, and pulsatile PRL and LH secretion were unaffected compared to those in control animals injected with hyperimmune serum.To determine whether GnRH is the PRL-releasing secretagogue responsible for concordant PRL and LH pulses, some rats were pretreated 4 h before blood sampling with a potent GnRH antagonist, followed by domperidone 30 min before sampling. Treatment with GnRH antagonist virtually abolished LH pulses, but had no effect on PRL pulses. It appears that neurons secreting some other PRL-releasing factor and loosely coupled to the hypothalamic GnRH pulse generator may be responsible for concordant hormone secretion.