M. E. Freeman

The hormonal factors associated with converting a corpus luteum of estrous cycle into a corpus luteum of pseudopregnancy were studied by measuring LH and FSH prolactin, estradiol and progesterone levels in decapitated rats during the 4-day estrous cycle and a comparable time of pseudopregnancy (lights on 0600-0800 hr.). During the estrous cycle, prolactin, LH and FSH remained low and unchanging except on the afternoon of proestrus, when typical proestrous surges were observed. In contrast, estradiol levels began to increase on D-1, from baseline values of 7 pg/ml to approximately 15-20 pg/ml. These levels were maintained until the afternoon of D-2 when estradiol further increased to reach peak levels of 40-50 pg/ml by 0900 hr on proestrus. Estradiol then declined in relation to the increase in LH secreation and had returned to baseline by estrus. Progesterone secretion by the corpora lutea of the cycle also increased on the afternoon of D-1 and reached a maximum value of 25-30 ng/ml early on the morning of D-2. At this time, a precipitious fall in progesterone occurred, returning to baseline values of 5-1- ng/ml by 0700 on D-2 signifying the regression of the corpora lutea of the cycle. Progesterone remained low thereafter until the afternoon of proestrus when levels increased in response to the proestrus when levels increased in response to the proestrous surge of LH. Following cervical stimulation at 1900 hr on proestrus, no differences were noted, with respect to the estrous cycle, in LH, FSH or estradiol secreation through the afternoon of D-2. Surprisingly, progesterone levels did not differ in the cycle and pseudopregnancy until the early morning of D-29 instead of progesterone levels falling to baseline as they had during the cycle, the corpora lutea of pseudopregnancy were rescused, progesterone increasing dramatically to reach levels of 45-50 ng/ml by 1700 hr on that same day. The only difference in hormone secretion that was noted which could account for this marked divergence in progesterone secretion was the pattern of prolactin secretion following cervical stimulation. In contrast to the low levels seen during the estrous cycle, biphasio surges of prolactin secretion occured each day, one being nocturnal (0100-0900 hr) and the other diurnal (1500-2100 hr). The rescue of the corpus luteum occured in association with the nocturnal surge on D-2. These results suggest that nocturnal surge on D-2, PROLACTIN IS THE MAJOR Luteotropic stimulus which transforms and estrous cycle into pseudopregnancy by prolonging progesterone secretion from the corpus luteum. Moreover, if LH is important for progesterone secretion, no changes were observed in the pattern of LH secretion which can account for the rescue of the corpus luteum.

Cervical stimulation in the rat institutes a pattern of prolactin secretion consisting of two daily surges, one diurnal and one nocturnal, which continue for the greater part of pseudopregnancy. This contrasts with the diestrous day 1–2 interval of the estrous cycle wherein prolactin levels are low and relatively unchanging. A variety of noxious procedures such as aortic cannulation and serial blood sampling, sham ovariectomy and sham surgical cuts in the hypothalamus selectively and temporarily suppresses the diurnal prolactin surges of pseudopregnancy; the nocturnal surges remained unaffected. In the absence of the ovaries (removed on day 0 of pseudopregnancy) the diurnal prolactin surges have disappeared no later than day 5, whereas the nocturnal surges are present at day 6 but have disappeared by day 10. Hypothalamic retrochiasmatic cuts abolish immediately both surges. These results demonstrate the existence of an apparently unique kind of neuroendocrine reflex, copulation-induced, which results in repeated nocturnal surges of prolactin secretion at daily intervals for a prolonged period of time in response to a brief 1-min stimulus. To account for these observations, a hypothalamic “mnemonic system” has been postulated which is activated by cervical stimulation and which retains and expresses this information repeatedly even in the absence of the ovaries. (Endocrinology94: 875, 1974)

An antiserum to estradiol was used to examine the role of estrogens secreted at diestrus in stimulating the proestrus surges of prolactin and luteinizing hormone (LH) secretion in the rat. Plasma prolactin and LH concentrations were measured by radioimmunoassay in blood samples obtained at 1–2 hr intervals on the day of proestrus in 4-day cyclic rats bearing aortic catheters. In control animals, proestrus prolactin values increased above baseline first at 1300 hr, were maximal between 1500–2000 hr, and returned to near baseline titers at 0100 hr on estrus. Proestrus LH concentrations were elevated first at 1500 hr, peaked at 1700–1800 hr, and fell to baseline values at 2300 hr. Estradiol antiserum administered at 1000 hr on proestrus did not affect the proestrus surge of prolactin and LH secretion or the incidence of vaginal cornification (100% vs. 94% in controls) and ovulation (88% vs. 71% in controls). On the other hand, estradiol∧ antiserum administered at 1000 hr on the day prior to proestrus (diestr...