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Am J Physiol Regul Integr Comp Physiol 278: R684-R691, 2000;
0363-6119/00 $5.00
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Vol. 278, Issue 3, R684-R691, March 2000

The neurosteroid allopregnanolone modulates oxytocin expression in the hypothalamic paraventricular nucleus

Brian J. Blyth1, Richard L. Hauger2,3, Robert H. Purdy2,3, and Janet A. Amico1,4,5

1 Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh 15261; 4 Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh 15261; 5 Department of Veterans Affairs Medical Center, Pittsburgh, Pennsylvania 15261; 2 Department of Psychiatry, University of California at San Diego; 3 Department of Veterans Affairs Medical Center, San Diego, California 92061

Virgin, ovariectomized rats exposed to 2 wk of sequential estradiol (E2) and progesterone (P) followed by P withdrawal have increased hypothalamic oxytocin (OT) mRNA and peptide levels relative to sham-treated animals. This increase is prevented if P is sustained. In the central nervous system, P is metabolized to the neurosteroid allopregnanolone (3alpha -hydroxy-5alpha -pregnan-20-one), which exerts effects by acting as a positive allosteric modulator of GABAA receptor/Cl--channel complexes. In the present study, ovariectomized rats that received sequential E2 and P for 2 wk followed by P withdrawal were administered allopregnanolone at the time of P withdrawal. Hypothalamic and plasma allopregnanolone concentrations, serum E2 and P concentrations, and hypothalamic OT mRNA levels were measured at death. Steroid-induced increases in OT mRNA were attenuated in animals treated with allopregnanolone at the time of P withdrawal. The results suggest that allopregnanolone plays an important modulatory role in steroid-mediated increases in hypothalamic OT.

estrogen; gamma aminobutyric acid; progesterone


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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
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Effect of 5{alpha}-pregnan-3{alpha}-ol-20-one on nitric oxide biosynthesis and plasma volume in rats
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2001; 280(6): R1902 - R1905.
[Abstract] [Full Text] [PDF]


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