Neurobiology of reproduction in the female rat. A fifty-year perspective.

With respect to the ovarian status and the estrous cycle as expressed by the vaginal cytology, it was emphasized that there is only a rough correspondence between the vaginal stages and the days of the cycle. The 4-day cycle tends to be the most frequent, with the 5-day cycle a normal variant. Spontaneous persistent vaginal estrus (SPE), an acyclic state occurring in older adult rats, reflects the presence in the ovaries of large vesicular follicles failing to luteinize and, hence, the absence of corpora lutea once the condition becomes well established. Pseudocyclic fluctuations in the vaginal smear during SPE resemble those in ovariectomized rats treated chronically with estrogen. The age of onset of SPE varies among different rat strains, appearing as early as 5 or 6 months in the DA and CD strains, but rarely before 12 months in the O-M strain. O-M/DA hybrids were intermediate. In the DA strain there was also a marked influence of length of daily illumination on the occurrence of SPE: exposure to 10 hours or less of light per day restored cycling to rats that had already shown SPE while exposed to longer days. An hereditary influence of age was also apparent in the rapidity with which continuous illumination induced persistent estrus (LLPE). Young DA females rapidly entered LLPE within 10 days, while young O-M females remained cyclic for 5 weeks. Hybrids again were intermediate. At middle age. O-M rats became as responsive as young rats of the DA strain. Like SPE in DA rats. LLPE was reversible, for estrous cycles returned after daily exposure to light was reduced. The special sensitivity of DA rats to lighting may have been a trait acquired from outcrossing with wild gray rats in years past. Normal cycling could be restored in SPE rats by daily injection of progesterone at low dosage. The same effect followed isolated treatments with progesterone upon return of proestrus/estrus after interruption of SPE. This was the first demonstration of positive feed-back of progesterone, the first sign of its biphasic action, and an indication that progesterone facilitates the action of estrogen in promoting ovulation. When progesterone treatment was delayed after proestrus/estrus there was progressively lower effectiveness during the next 10 days. Indirect support of regular ovulatory cycles resulted from treating DA SPE rats with prolactin (PRL) daily at low doses, provided that an initial set of corpora lutea was first induced by other means.(ABSTRACT TRUNCATED AT 400 WORDS)