Research reportDifferential regulation of oxytocin and vasopressin messenger ribonucleic acid levels by gonadal steroids in postpartum rats
Introduction
During the 48 h preceding and following parturition, dramatic changes in oxytocin (OT) and arginine vasopressin (AVP) mRNA levels occur in the hypothalamic paraventricular and supraoptic nuclei (PVN and SON) of the rat [3]. OT and AVP mRNA levels are at their peak at term (day 21 of gestation) 7, 11, 12and precipitously decline after delivery [3]. We recently reported that the changing pattern of gonadal steroid hormones that occurs during pregnancy and lactation accounts for these changes in OT and AVP mRNA levels 4, 9. Specifically, rising estrogen levels during pregnancy combined with declining progesterone and testosterone levels at term account for the increases in OT and AVP mRNAs, respectively 4, 9. If progesterone levels are sustained on day 21 of pregnancy, OT, but not AVP, mRNA levels are attenuated [4]. If testosterone levels are sustained at term, AVP mRNA levels are attenuated [9]. Thus, progesterone and testosterone are inhibitory to OT and AVP expression, respectively. In the setting of prior estrogen priming, the declines in progesterone and testosterone are stimulatory to OT and AVP mRNAs, respectively.
The peak levels of OT and AVP mRNA levels at term are not sustained following delivery [3], possibly due to the changing gonadal steroid milieu postpartum. During week one postpartum, estrogen levels are low [6], except for the brief postpartum surge of estradiol that occurs with the postpartum estrus [5], progesterone levels rise [6]and both OT and AVP mRNA levels are attenuated compared to term levels [3]. Thus, even if estrogen alone were sustained postpartum, OT mRNA levels might not increase because progesterone, which is inhibitory to OT expression [4], rises postpartum. On the other hand, the increase in AVP mRNA at term pregnancy might persist postpartum if estrogen levels were sustained because there is no postpartum rise in testosterone [8], which is inhibitory to AVP mRNA [9]. To test this hypothesis, we determined the effects of sustaining estrogen during early lactation upon PVN OT and AVP mRNA levels. We report that estrogen supplementation sustains AVP, but not OT, mRNA levels in early lactation.
We also used a second experimental paradigm in the ovariectomized rat to determine whether the ‘upregulatory’ effects upon OT of progesterone withdrawal in the estrogen-primed rat is dependent upon sustaining estrogen after progesterone levels decline. In a prior report [4], sequential estrogen and progesterone administration to, and subsequent progesterone removal from, ovariectomized rats increased OT mRNA. In that study, estrogen was maintained at the time of progesterone withdrawal. In the present study, we maintained estrogen at the time of progesterone withdrawal and compared this effect to simultaneously withdrawing both. We now report that progesterone withdrawal is critical to the increase in OT mRNA, irrespective of whether estrogen is maintained or simultaneously withdrawn.
Section snippets
Animals and tissue removal
First-time pregnant Sprague-Dawley rats weighing 250–300 g (experiment 1) or 225–250 g ovariectomized Sprague-Dawley rats (experiment 2) were obtained from Zivic-Miller laboratories (Allison Park, PA) and were housed in plastic maternity cages or mesh cages, respectively, under controlled conditions (lights on 0600–1800 h; room temperature, 22°C). Laboratory rat chow (Wayne Lab-Blox, Chicago, IL) and water were available ad libitum. For the lactation studies, animals delivered on site and
Experiment 1
At sacrifice on day 2 of lactation, estradiol levels were higher in the estradiol- vs. sham-implanted group (25 ± 4 vs. 5 ± 0.4 pg/ml, respectively, P < 0.002), but progesterone levels were not significantly different (32 ± 5 vs. 27 ± 2 ng/ml, respectively). Despite the differences in estradiol levels, PVN OT mRNA levels were not significantly different between the two groups, Fig. 1A. In contrast, PVN AVP mRNA levels were significantly higher in animals receiving estradiol-filled implants, P <
Discussion
The 48 h prior to and after delivery in the rat are accompanied by rapid fluxes in circulating levels of estrogen, progesterone and testosterone. Progesterone and testosterone levels, which rise during gestation, precipitously decline prepartum 1, 2. Twenty-four hours after delivery progesterone, but not testosterone, levels begin to rise 5, 6, 8. Estrogen levels are high during gestation but remain low (< 10 pg/ml) during the first week of lactation [6], except for the brief postpartum surge
Acknowledgements
This project was supported by funds from the Department of Veterans Affairs (J.A.A.). A.T. was supported by NIH grant 5T32-DK-0752 for training in Endocrinology and Metabolism. J.A.A. was a recipient of a Career Development Award from the Department of Veterans Affairs. Presented as an abstract at the annual meeting of the Society for Neuroscience, November 13–17, 1995, San Diego, CA.
We thank Dr. Thomas Sherman for the rat OT and AVP cDNAs, and Dr. Stephen Phillips for the mouse β actin cDNA.
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