THE DURATION OF ESTRADIOL AND PROGESTERONE EXPOSURE PRIOR TO PROGESTERONE WITHDRAWAL REGULATES OXYTOCIN MESSENGER-RNA LEVELS IN THE PARAVENTRICULAR NUCLEUS OF THE RAT

The nonapeptide oxytocin (OT) is important for milk ejection during la ctation, uterine contractility at parturition, and the onset of matern al behavior. Sequential exposure to estradiol (E-2) and progesterone ( P) followed by P withdrawal increases OT mRNA in the paraventricular n ucleus (PVN), and to a lesser degree the supraoptic nucleus (SON), of the rat 48 hours after the P is removed. Although increases in PVN OT mRNA are not accompanied by changes in posterior pituitary OT peptide content, the PVN contains OT neurons that project to both the posterio r pituitary (magnocellular group) and extra pituitary sites (parvocell ular groups). Steroid-induced increases in OT mRNA occur in both the m agnocellular and the parvocellular regions of the PVN. The latter are believed to contribute to CNS release of OT which may be important for certain behaviors including the onset of maternal behavior. The same steroid sequence that increases PVN OT mRNA also induces maternal beha vior in virgin ovariectomized rats. Exposure of animals to E-2 and P f or 2 weeks resulted in the shortest latency to the onset of maternal b ehavior in ovariectomized rats, whereas exposure for 6 days was associ ated with a longer latency. In this study we questioned if the duratio n of E-2 and P exposure prior to P withdrawal is an important regulato r of PVN OT mRNA levels. We compared OT mRNA levels in the PVN of virg in ovariectomized rats administered no steroid or sequential E-2 and P for 2 weeks versus 6 days. On day 1 animals received steroid-filled o r empty capsules followed by by P-filled or empty capsules on day 3. I n one steroid-treated group, E-2 and P were continued for 6 days and i n the other group for 14 days prior to P removal. Animals were sacrifi ced 48 hours after P removal. bevels of OT mRNA were compared among 6 day and 2 week steroid-treated animals and sham-treated animals. The r elative abundance of OT mRNA was significantly increased, P < 0.05, in animals receiving the 2-week, but not the 6-day, steroid treatment co mpared to sham-treated animals. Pituitary OT peptide content was not s ignificantly different among the three groups. We conclude that the du ration of steroid exposure may be an important regulator of the level of OT mRNA in the PVN of the rat.