Receptor-Mediated Interrelationships between Progesterone and Estradiol Action on the Anterior Pituitary-Hypothalamic Axis of the Ovariectomized Immature Rat*

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Abstract
The ovariectomized immature rat was used as a model for analysis of action of progesterone as a modulator of receptor-mediated functional responsiveness in the anterior pituitary and hypothalamus. In response to estrogen exposure, cytosolic progesterone receptors appear rapidly, rise in concentration to a peak at 12 h, then fall to a plateau level well above control, which is maintained for at least an additional 20 h. Progesterone administration at the peak 12-h interval induces maximal nuclear accumulation of its own receptor within 1-2 h, with apparent extensive processing occurring thereafter. To this point, no differences were seen between anterior pituitary and hypothalamic responses. If animals were administered progesterone (0.8 mg/kg BW) at the 12-h peak interval, subsequent nuclear accumulation of anterior pituitary estrogen receptor by an injection of estradiol was suppressed if, and only if, the interval between progesterone and estradiol injection did not exceed 2 h; at no time interval did progesterone have an effect in the hypothalamus. In both tissues, estradiol readministration at 12 h after an initial injection stimulates a second wave of progesterone receptor activity, again peaking 12 h later. A single injection of progesterone 1 h before the second estradiol administration blocks the second peak of progesterone receptor in the anterior pituitary, but not in the hypothalamus. If the interval between the progesterone and second estradiol injections is extended to 4 h, the second progesterone receptor peak appears as though no progesterone had been introduced. The results indicate a critical temporal reliance of the inhibitory effects of progesterone on estrogen receptor activity and estrogen function in a well defined animal model. The effect is progesterone receptor-mediated and is manifested in the anterior pituitary, but not in the hypothalamus, even though the kinetics of estrogen-induced progesterone receptor activity are indistinguishable between the two tissues.