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E. S. KISCH

The induction of pseudopregnancy in the rat abolishes, for about 8 days, the hypothalamic inhibition of pituitary luteotrophic hormone (lth) secretion (Zeilmaker, 1965). Pituitary lth is available throughout this period, whether functional corpora lutea are present or not. If a new oestrus is induced during this 8-day period, this oestrus is followed by a fresh pseudopregnancy of normal length, still benefiting, as it were, from the prior stimulus which initiated lth secretion and induced the first pseudopregnancy; the stimulus is `remembered' in the central nervous system (Everett, 1967).

Ergocornine interrupts progestation in the pregnant and pseudopregnant rat, and oestrus appears within 2 to 3 days of administration of the ergot alkaloid (Shelesnyak, 1955). This oestrus, caused by the interruption of gestation, is followed in 50 to 70% of cases by

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E. S. KISCH and M. C. SHELESNYAK

Summary.

An attempt was made to test whether modification of the ergocornine molecule (eco) by the liver is a prerequisite to its pregnancyinterrupting action, and whether the liver plays a role in the elimination of the drug from the organism. For this purpose eco was administered to the perfused rat liver and into the portal bed of the pregnant rat. The effectiveness of the drug in terminating progestation when administered by these routes was less than one-fourth the effectiveness following systemic injections. Attempts to recover biologically active eco from the bile and the liver itself failed. This suggests inactivation of the ergot alkaloid by the liver.

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E. S. KISCH and M. C. SHELESNYAK

Summary.

A single administration of ergocornine methanesulphonate (eco) interrupts pregnancy of the rat when given on any day until the 7th after coitus, but not later. The drug also interrupts pseudopregnancy at any time during its course, without temporal limitation. The failure of eco to interfere with pregnancy is correlated with the presence and endocrine activity of an implanted conceptus.

The factors causing failure of eco to interfere with gestation after implantation were identified by a series of successive steps : (1) The presence of deciduomata—thought to be analogous to maternal decidual tissue—in the pseudopregnant uterus was shown not to oppose eco action. (2) Animals, whose foetuses have been removed, leaving only maternal and foetal placenta in situ, were protected against the action of eco. Thus, this implicated by elimination the foetal placenta as causing failure of eco action in pregnancy after the 7th day. Indeed, placental grafts from late pregnant donors could be shown to overcome eco action even in this first 7-day period.

As early as the 10th day, a luteotrophic influence was present in placental extracts, as measured by prevention of eco action on pregnancy. In the literature, a luteotrophic influence is attributed to (foetal) placental tissue. The failure of eco to interrupt pregnancy by the 8th day is taken as indication of placental luteotrophic activity at that time, i.e. 3 days before it can be detected when hypophysectomized rats are used for this purpose.

The action of eco is considered as mediated by pituitary lth depression. Thus, the use of this drug allows suppression of lth without performing hypophysectomy. Placental luteotrophin is not affected by eco.