Allopregnanolone modulates oxytocin in hypothalamic OT

The neurosteroid allopregnanolone modulates oxytocin expression in the hypothalamic paraventricular nucleus.

[NOTE: FINASTERIDE INHIBITS ALLOPREGNANOLONE VIA BLOCKAGE OF PROGESTERONE – view http://jpet.aspetjournals.org/cgi/content/full/288/2/679 to learn how]

FULL TEXT:
ajpregu.physiology.org/cgi/conte … 278/3/R684


ABSTRACT:

Virgin, ovariectomized rats exposed to 2 wk of sequential estradiol (E(2)) and progesterone § 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.