Flurkey K, Randall P K, Sinha Y N, Ermini M, Finch C E
Biol Reprod. 1987 May;36(4):949-59. doi: 10.1095/biolreprod36.4.949.
Regular estrous cycles can be reinitiated in old acyclic female rats by pharmacologic, hormonal, and environmental manipulations. The most responsive acyclic states are persistent vaginal cornification (PVC) and spontaneous pseudopregnancy (SP). However, it is not known if the irregular cyclicity that precedes acyclicity during aging can also be alleviated. We found that transient shortening of estrous cycles follows smear sequences indicative of pseudopregnancy in C57BL/6J mice, aged 9-15 mo, suggesting a role for progesterone. This phenomenon was investigated through a limited model of pseudopregnancy in which intact aging mice with lengthened cycles were given progesterone implants (yielding 70 ng progesterone/ml plasma) that suppressed estrous cycles; upon removal of the implants, cycles were transiently shortened in aging mice. Therefore, we hypothesize that withdrawal from the progesterone elevations associated with SP is the mechanism in shortening subsequent estrous cycles. Effects of central-acting drugs, similar to those used to reinitiate cyclicity in acyclic old rats, were also examined. Hydergine, an ergot mixture with partial dopaminergic and serotonergic agonist activities, suppressed SP when fed to 10- to 12-mo-old, middle-aged mice. Hydergine did not otherwise affect estrous cycle length, prevent PVC, or reinitiate cycling in acyclic PVC mice. Feeding L-dihydroxyphenylalanine to middle-aged mice did not suppress SP, affect estrous cycle lengths, or reinitiate cycles from PVC.
通过药理学、激素和环境操作，可使老龄无发情周期的雌性大鼠重新建立规律的发情周期。最易产生反应的无发情周期状态是持续性阴道角化（PVC）和自发性假孕（SP）。然而，尚不清楚衰老过程中无发情周期之前出现的不规律周期是否也能得到缓解。我们发现，在9至15月龄的C57BL/6J小鼠中，发情周期短暂缩短遵循指示假孕的涂片序列，提示孕酮起了作用。通过一个有限的假孕模型对这一现象进行了研究，在该模型中，给周期延长的老龄完整小鼠植入孕酮（使血浆中孕酮含量达到70 ng/ml），从而抑制发情周期；取出植入物后，老龄小鼠的周期短暂缩短。因此，我们推测，与自发性假孕相关的孕酮水平升高的消退是缩短后续发情周期的机制。还研究了与用于使老龄无发情周期大鼠重新建立周期的药物类似的中枢作用药物的效果。双氢麦角碱是一种具有部分多巴胺能和5-羟色胺能激动剂活性的麦角混合物，给10至12月龄的中年小鼠喂食时可抑制自发性假孕。双氢麦角碱在其他方面不影响发情周期长度、预防持续性阴道角化，也不能使处于持续性阴道角化状态的无发情周期小鼠重新开始有周期。
