A Discontinuous Schedule of Estradiol Treatment Is Sufficient to Activate Progesterone-Facilitated Feminine Sexual Behavior and to Increase Cytosol Receptors for Progestins in the Hypothalamus of the Rat

In this study, we demonstrate that a surprisingly small and discontinuous period of estradiol (E2) treatment is sufficient to induce progesterone-facilitated sexual receptivity in the female rat. We used this temporal paradigm to measure associated changes in nuclear E2 and cytosol progestin receptors (CPRs) in the mediobasal hypothalamus-preoptic area (MBHPOA) and pituitary (PIT). The lordosis quotient, lordosis quality, and preceptivity scores of animals which received E2 in Silastic capsules for 24 or 6 continuous h were not significantly different at 24 h. CPRs in the MBH-POA and PIT in animals which received E2 for 24 or 6 continuous h were equivalent at 24 h. Receptivity comparable to 24 or 6 h of continuous E2 treatment was seen in animals which received only two 1-h periods of E2, provided that the second treatment began not fewer than 4 h, or more than 13 h, after the end of the first period (sufficient treatment). If animals received only two 0.5-h periods of E2 treatment during these times, receptivity was not observed (insufficient treatment). Sufficient treatment was associated with a threshold level of CPRs in the MBH-POA (25–35% maximal induction), whereas insufficient treatment was not. Our hour of E2 treatment produced twice the level of nuclear estradiol receptors (NERs) as did 0.5 h of E2 in the MBH-POA and PIT. After capsule removal, NER levels in the MBH-POA and PIT sharply decreased in both the 1 and 0.5 h treatment groups. The time course of decline of NER levels was a first order process, with a alf-life of 3.5 h in the MBH-POA. We conclude that two periods of E2 treatment with a total exposure time of 2 h during 24 h are sufficient to activate the lordosis reflex and elevate CPRs to threshold levels in the hypothalamus. An essentially discontinuous (≤3.6% NER capacity between two peaks) pattern of NER levels in the nuclei of hypothalamic cells is associated with these changes.