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.
Several blood steroids, serum gonadotropins and cytosol estradiol receptors of the anterior pituitary and hypothalamus were quantified in immature female rats which were induced to ovulate with pregnant mare's serum gonadotropin (PMSG). Studies revealed that serum levels of progesterone, 17-hydroxyprogesterone, testosterone, androstenedione and estradiol were initially elevated at 6 PM (day 30) after administration of 8 IU of PMSG at 10 AM day 30. Serum levels of estradiol and testosterone rose progressively from day 30 through the AM of day 32. A further increase in serum concentrations of progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, and dehydroepiandrosterone occurred on the PM of day 32 whereas serum estradiol levels declined. Serum levels of all steroids declined on the day of estrus (33) and only progesterone levels were further elevated on day 34 (diestrus). Dihydrotestosterone concentrations were minimally altered by PMSG treatment. Saline administration resulted in no significant alterations in levels of any steroid quantified from day 29 to 34 in control animals. A progressive decline in cytosol estradiol receptor content of the anterior pituitary and hypothalamus was documented following PMSG treatment of intact female rats; there was no depletion of receptors following PMSG administration to ovariectomized immature rats. Maximal depletion of cytosol estradiol receptors occurred on day 32 with replenishment of cytosol estradiol receptor levels on estrus (day 33). The preovulatory gonadotropin surge was found to occur on the PM of day 32 after maximal receptor depletion. The cycle of depletion and replenishment of receptors was repeated during a second spontaneous estrous cycle four days later which coincided with a rise and fall in serum estradiol levels. It is suggested that the depletion of cytosol estradiol receptors of the anterior pituitary/hypothalamic unit may be causally related to the preovulatory gonadotropin surge resulting from PMSG administration to immature female rats. In addition, changes in blood steroids and gonadotropins after PMSG treatment are similar to those reported for proestrus-estrus-diestrus I of the normal adult estrous cycle. These findings further demonstrate the validity of the PMSG-primed immature female rat preparation as a model for the estrous cycle of the adult rat.
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