Reinstatement of Estrous Cycles in Middle-Aged Spontaneously Persistent Estrous Rats: Importance of Circulating Prolactin and the Resulting Facilitative Action of Progesterone*

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Abstract
Spontaneous persistent estrus (SPE), although a common feature of senility, may occur in middle-aged rats. Thus, in Charles River CD rats it often appears in virgin females 6-12 months old. Whereas in aged SPE rats a single injection of LH is commonly followed either by pseudopregnancies (PSPs) in repetition or by PSP succeeded by a number of short estrous cycles, the usual result in middle-aged CD SPE rats is the immediate occurrence of I or more short cycles, after which SPE returns. Among 46 such animals, only 10 (22%) presented PSP, while 30 (65%) merely presented short cycles. The other 6 rats returned promptly to SPE after a brief diestrus. From these results it is postulated that events after a luteinizing dose of LH or the introduction of a set of corpora lutea by any other means are determined by the amount of basal PRL secretion in the days after treatment. If PRL is minimal, SPE returns promptly; if moderately elevated, short cycles appear because of low grade progesterone secretion from the corpora lutea; if PRL is at high level, PSP occurs, repeatedly if the high level is sustained. To test the hypothesis, 27 SPE rats were treated with either bromocryptine or lergotrile to impede PRL secretion during the initial diestrus after LH injection. SPE returned promptly in 22 rats (81.5%). The remaining 5 rats, having 1 or 2 short ovulatory cycles before being dispatched, are thought to have been animals that would have shown PSP if PRL secretion had not been reduced by the ergot alkaloids. In the majority of rats, by contrast, the reduction of PRL was evidently to such a low level that corpus luteum progesterone secretion was inadequate to promote an LH surge. When ovulatory cycles occur after interruption of SPE by luteinization, moderate secretion of PRL and moderate activation of corpora lutea appear to serve protective roles, with progesterone counteracting the lowered responsiveness of the hypothalamic-hypophysial system to estrogen. (Endocrinology106: 1691, 1980).