The neurosteroid allopregnanolone modulates oxytocin expression in the hypothalamic paraventricular nucleus.
Virgin, ovariectomized rats exposed to 2 wk of sequential estradiol (E(2)) 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 GABA(A) receptor/Cl(-)-channel complexes. In the present study, ovariectomized rats that received sequential E(2) and P for 2 wk followed by P withdrawal were administered allopregnanolone at the time of P withdrawal. Hypothalamic and plasma allopregnanolone concentrations, serum E(2) 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.
Blyth
B J
BJ
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Hauger
R L
RL
Purdy
R H
RH
Amico
J A
JA
D000818:Animals; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D010052:Ovariectomy; D010121:Oxytocin / Q000096:biosynthesis*; D011280:Pregnanolone / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats
D011374:Progesterone; D004958:Estradiol; D010121:Oxytocin; D011280:Pregnanolone