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The Effects of Progesterone on Oxytocin mRNA Levels in the Paraventricular Nucleus of the Female Rat Can Be Altered by the Administration of Diazepam or RU486 1
Author(s) -
; Thomas,
Shughrue,
Merchenthaler,
Amico
Publication year - 1999
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.1999.00294.x
Subject(s) - oxytocin , medicine , endocrinology , nucleus , diazepam , chemistry , biology , pharmacology , neuroscience
Oxytocin (OT) facilitates the onset of maternal behaviour in the late pregnant rat, enhances uterine contractility at parturition, and elicits milk ejection during lactation. If the rising estradiol (E 2 ) and declining progesterone (P) of late pregnancy is reproduced in a virgin ovariectomized rat by implanting E 2 ‐ and P‐filled capsules for 2 weeks followed by removal of P‐containing implants 36–48 h prior to death, OT messenger ribonucleic acid (mRNA) levels increase in the paraventricular and supraoptic nuclei (PVN and SON) of the rat. Both E 2 administration and P withdrawal are necessary to increase OT mRNA, but the mechanisms of these effects are not understood. P may work within the PVN although P receptors are reported to be sparse or non‐existent in the PVN or outside the PVN on PR‐containing neurones that project to OT‐containing neurones or via membrane bound receptors that are known to bind neurosteroids and gamma aminobutyric acid (GABA). To determine the mechanism through which P may inhibit or P withdrawal may increase OT mRNA levels, virgin ovariectomized (OVX) rats received sequential E 2 and P via Silastic implants for 14 days. On day 13, prior to removal of P capsules on day 14, the rats were given the benzodiazepine agonist, diazepam, or saline injections subcutaneously (s.c.) twice daily until death on day 16. OT mRNA levels were increased in the steroid‐treated group that received saline but not diazepam. In experiment 2, P capsules were removed on day 14 or pharmacological P withdrawal was induced by injecting RU486 injections s.c. twice daily until death 48 h later. OT mRNA levels were increased in the steroid‐treated group that received RU486. Subsequent studies demonstrated the expression of PR mRNA within the rat PVN. The data suggest that gonadal steroids may influence PVN OT mRNA levels by modulating the GABA A receptor or by directly altering gene transcription via the PR.