The effect of hypophysectomy on day 12 of pregnancy on the serum progesterone level and time of parturition in the rat.

Pregnant rats were either hypophysectomized or sham-hypophysectomized on day 12 (day 1: day of insemination) or unoperated on, and observed for the changes in the concentration of progesterone in peripheral serum and the time of parturition. Progesterone was measured by protein binding displacement; blood samples were collected serially in some rats and at autopsy in others between days 15 and 26. A large group of samples from rats in other experiments furnished values for the level on day 12. In both intact and hypophysectomized rats the mean serum progesterone level increased from 87.1 ng/ml on day 12 to about 130 ng/ml on day 15 and slowly fell to about 100 ng/ml on day 19. After day 19, the level continued to fall in the hypophysectomized rats at about the same rate as before, while in the intact rats, the rate of fall increased to about 10 times that present before day 19. All but 2 of 14 intact rats delivered on days 22 or 23; out of 15 hypophysectomized rats observed to term only 5 delivered, 3 of them on days 24 or 25. Of the other 10, 2 died on day 23, and 8 were killed or died between days 24 and 26. These findings, which indicated a strong but not absolute relationship between the fall in serum progesterone level and the onset of parturition, were interpreted to be discordant with the hypothesis (1) that luteinizing hormone (LH) is the essential luteotroohin during pregnancy in the rat. {Endocrinology 91: 1380, 1972) I HAS BEEN postulated that the essential luteotrophic stimulus during pregnancy in the rat is luteinizing hormone (LH) and that a deficiency of LH secretion after day 12 is specifically responsible (1) for the decline in progesterone secretion (2-8) which occurs prior to parturition in intact rats. This hypothesis, however, does not appear to be consistent with some of the effects of hypophysectomy in the pregnant rat. For example, although hypophysectomy before day 11 (day 1: day of insemination) practically always and promptly causes abortion, hypophysectomy on day 11 or 12 does not; in fact, pregnancy is not only maintained, but is usually prolonged beyond term and is frequently associated with abnormal and difficult labor (9-11). Treatment with progesterone also prolongs pregnancy (1,12,13) and it is possible, therefore, that the marked tendency for hypophysectomy to delay parturition is an expression of such an effect of progesterone; from the condition of the mammary glands, vaginas, and uteri, in fact, Alloiteau et al. (14) sugReceived April 7, 1972. 1 Supported by USPHS-NIH Training Grant HD00024, NIH Contract 70-2310, and Ford Foundation Training Grant 67-135. 2 Postdoctoral Trainee in Reproductive Biology (NIH TG HD-00024). gested that hypophysectomy causes a prolongation of progesterone secretion in the pregnant rat. These facts seemed to be sufficient reason to doubt the validity of Raj and Moudgal's hypothesis (1), since the hypophysectomized rat must surely secrete less LH than the intact one. The following experiment, therefore, was done. It was designed to compare the intact with the hypophysectomized pregnant rat for changes in the serum progesterone level between day 12 and term. Materials and Methods General. All rats (Sprague-Dawley strain; Holtzman Rat Company, Madison, Wisconsin) were bred in the laboratory, day 1 of pregnancy being considered as the day of insemination. They were maintained in plastic cages, with free access to Purina® Rat Chow and water, under a fixed lighting schedule of 14:10 hr of light:darkness. The experimental rats were hypophysectomized by the parapharyngeal route on day 12; control rats were either sham-hypophysectomized or were not operated on. Since no differences were found in either serum progesterone levels or duration of pregnancy between the two groups of intact rats they will henceforth be considered as one group, the intact controls. Ether was used as anesthesia for all operations and for the collection of blood samples. Completeness of hypophysectomy was determined by examination of the pituitary fossa at autopsy and by comparing the wt of the