The Nature and Control of the Ante-Partum Prolactin Surge in the Rat

Abstract

Plasma prolactin (PRL) levels are elevated during late pregnancy in the rat. While this ante- partum PRL rise is well established, the nature and the control of PRL secretion at this time have not been well studied. The aim of this study was to determine the pattern of PRL secretion in the last three days of pregnancy in the rat, and to investigate the mechanisms controlling PRL secretion at this time. Blood samples were collected at regular intervals from conscious, unrestrained rats by means of previously implanted jugular cannulae from day 19 of pregnancy until parturition. Plasma PRL was measured by radioimmunoassay. In untreated control rats, which usually gave birth during the light period of either day 21 or day 22 of pregnancy, plasma PRL remained basal (<10 ng/ml) until day 20 of pregnancy, when levels gradually increased to approximately 30 ng/ml. In the night preceding parturition a large nocturnal surge of PRL began at approximately 2200 h and peaked at >300 ng/ml between 0300 and 0500 h PRL levels then gradually fell to approximately 50 ng/ml by 1200 h on the day of parturition. The surge always peaked at the same time of day regardless of the time of parturition, demonstrating that PRL secretion during late pregnancy delayed parturition Progesterone treatment from day 19 until day 21 of pregnancy delayed parturition for 20-24 hours, and prevented the occurrence of the PRL surge until the night after the treatment was stopped. Estradiol treatment following ovariectomy on day 19 advanced parturition, and also advanced the appearance of the nocturnal PRL surge by 24 hours. Placental lactogen (PL) had no effect on PRL secretion during late pregnancy, as removal of all but 1 or 2 conceptuses oh day 19 did not affect the timing of the ante-partum PRL surge. Similarly, icv injection of human PL which totally abolished both the nocturnal and diurnal surges of PRL during early pregnancy, had no effect on the ante-partum PRL surge. Removal of all conceptuses (FPX) on day 19 induced a premature PRL surge, apparently due to the reduction in progesterone following FPX, as progesterone treatment following FPX significantly reduced PRL secretion. Consistent with the absence of an inhibitory effect of PL, autoregulation of PRL secretion did not occur during-late pregnancy, since intrahypothalamic anterior pituitary-grafts that elevated PRL in the cerebrospinal fluid had no effect on the ante-partum PRL surge. Antagonists of vasoactive intestinal peptide and endogenous opioids inhibited the PRL surge, whereas antagonists of oxytocin and serotonin had no effect. Chronic removal of the posterior lobe of the pituitary also had no effect. These results suggested that following the fall in progesterone levels during late pregnancy, PRL secretion Simulated in a nocturnal surge which is .promoted by estradiol and a neurohormonal mechanism involving vasoactive intestinal peptide and opioid peptides. This mechanism was clearly linked to the daily light/dark cycle. The ante-partum PRL surge appeared to be involved in stimulating lactogenesis prior to parturition. Specific inhibition of the surge using the dopamine agonist CB-154 significantly inhibited the cytological differentiation of the mammary epithelial cells on the last day of pregnancy, preventing the rapid extrusion of secretory material from the cells that normally occurs 8-12 hours before parturition.