SynopsisIn order to elucidate the facilitation of ovulatory release of luteinizing hormone (LH) and subsequent ovulation, subcutaneous injection or intrahypothalamic implantation of progesterone was carried out on the morning of proestrus in 4-day cyclic rats . By injecting progesterone on the morning or early afternoon of proestrus , an approximate 3 hr advancement of ovulatory release of LH was demonstrated by confirming the occurrence of ovulation on the next morning after timed hypophysectomy performed on the afternoon of proestrus. Ovulation also occurred about 3 hr earlier in the estrous morning when progesterone had been given on the morning of proestrus. The minimum effective dose of progesterone to facilitate LH-release was somewhere between 0 .1 and 0.625mg per rat. Facilitation of LH-release by steroid administration on the morning of proestrus is not entirely specific for progesterone. Norethisterone, medroxyprogesterone acetate , and desoxycorticosterone(DOC) also induced the advanced release of LH. Facilitation of ovulatory release of LH was induced also in the rats having progesterone crystals implanted in the median eminence-arcuate region of the hypothalamus on the morning of proestrus. These results indicate that a neural timing factor regulating the onset of LHrelease in proestrus is labile to a certain extent, and that it operates about 3 hr in advance when it is exposed to progesterone given on the morning of proestrus , and that the appearance of facilitatory action of progesterone depends on the pre-existing estrogen level in the circulating blood.It is well known that progesterone has a biphasic effect on ovulation and, according to the conditions, it can either stimulate or inhibit the release of luteinizing hormone (LH) (for a review see Everett, 1964; Sawyer, 1964;Rothchild, 1965;Davidson, 1969). A lack of spontaneous ovulation during pregnancy or pseudopregnancy is evidence of the inhibitory effect on LH-release of endogenous progesterone, the secretion of which is increased during gestation. Exogenous progesterone also inhibits or delays spontaneous ovulation in rats and in many other species. The stimulating effect of progesterone on ovulation has been shown under several conditions, e. g. in persistent estrous rats (Everett, 1940), in normal 5-day cyclic rats (Everett, 1948; BrownGrant, 1967) and in immature rats primed with pregnant mare's serum gonadotropin Meyer, 1963 and1965).With regard to the ovulation induction in adult rats, it was previously suggested by Everett(1948) that the appearance of stimulating action of progesterone depends on the pre-existing estrogen level in the circulating blood. In our previous work, progesterone administered into 4-day cyclic rats induced a delayed ovulation only when injected before 2 a. m. proestrus, by which time estrogen secretion had not attained the maximum (Hori et al., 1968), and it accounted for uterine distension and uterine weight increase on the day of proestrus though it was not enough for the release of LH on the same day (Kob...