Pregnant rats, hypophysectomized-hysterectomized on day 12 (day 1=insemination), secreted progesterone (P) at about 50% of the day 12 level for 3-5 days. Daily treatment with estradiol 100 microng (E100) but not with E25 or E50, from day 12 to day 20, of such rats, restored P secretion until day 16 to that of intact pregnant rats; on day 17 a drastic permanent fall occurred. E100 had no effect after ovariectomy, and did not change the metabolic clearance rate of P. This E100 effect was absent in decidual tissue (DT)-bearing, or hysterectomized pseudopregnant (PSP) rats, and in pregnant ones before day 11. When pregnant rats were hypophysectomized-hysterectomized on day 10, and were treated with rat placental luteotrophin (rPL) (in the form of day 12 pregnant rat serum: "PRS-12") on days 10 and 11, however, E100 increased P secretion above that found with either PRS-12 or E100 alone. DT-bearing PSP rats, similarly operated on on day 12 and treated with PRS-12 on day 12, responded in the same way to E100. In these rats also the E100 effect lasted for four days. In the day 12 hypophysectomized-hysterectomized pregnant rat, the E100 effect could not be prolonged by single treatments with PRS-12 on either days 13, 14 or 16, but when PRS-12 was given daily from day 12 to 19, P was secreted until day 20 only slightly below the day 12 level; this treatment plus E100 raised P secretion, prolonged it to day 18, and led to a marked fall by day 20 similar to that of the intact pregnant rat at term. The marked increase in P secretion between days 12 and 15 of normal pregnancy may thus be a response to intraluteal estrogen; the pattern of P secretion from day 12 to term may reflect the effects of both estrogen and rPL. rPL probably induces this effect by generating luteal estrogen and LH receptors. The placenta may also secrete an LH-like hormone (rCG?) which, through the LH receptors, could stimulate intraluteal estrogen production.

At one of four stages during the period of corpus luteum (CL) activity (day 9, day 12, day 15, or day 18) groups of hysterectomized pseudopregnant (PSP) rats and of intact pregnant (PRG) rats were compared for the effect of a single sc injection of an antiserum to LH (LH-AS) on progesterone secretion. Groups of control rats were injected sc with normal horse serum (NHS) at these same stages, and in all rats, the progesterone level in jugular blood serum was measured by RIA on the day of treatment and 24 and 72 h after treatment. Among the PRG rats, the controls' progesterone levels rose to a peak on day 15, and then slowly declined. LH-AS on day 9 induced abortion and a rapid, drastic and permanent fall in the progesterone level in all rats. On day 12, it induced a similar fall in progesterone, and abortion, in 4 of 10 rats; in the 6 which remained pregnant, a much less severe fall occurred 24 h after treatment, and by 72 h the level had returned to close to the initial one. On days 15 or 18, LH-AS induced neither abortion nor a significant change in the progesterone level from that seen in the controls. Among the PSP rats, the controls' progesterone levels tended to fall progressively after day 9; the average length of diestrus was about 21 days. At each of the four stages the LH-AS induced a rapid, drastic and permanent fall in the progesterone level. Early termination of the diestrus was easily discernible in the groups injected on days 9 or 12, but was obscured in the other groups because of the similarity in length of the expected remaining diestrus and the duration of the neutralizing effect of the LH-AS on LH in the circulation. The PSP rats' CL, thus, once they become dependent on LH (about day 9), remain so to the end of PSP. The PRG rats' CL seem to lose this dependency after day 12, but the possibility could not be eliminated that the dependency may shift from LH to a placental LH-like hormone.