Effects of adrenalectomy on reproduction in the mouse.

Survival of mice treated with sesame seed oil after adrenalectomy was very low and suggested no beneficial effect, whereas treatment with progesterone improved the chances of survival. Treatment with desoxycorticosterone acetate (DOCA) and methyl prednisolone acetate also increased the number of animals surviving after adrenalectomy. The corticosteroids were significantly more effective in ensuring survival than was progesterone. There was no significant difference in survival between mice receiving a single injection of 1.0 mg DOCA and those being given an injection of 1.0 mg DOCA per day for 3 days after the operation. To ensure minimum interference of exogenous corticosteroid with the experimental investigation, animals routinely received only a single injection of 1.0 mg DOCA after the operation. The chance of survival after adrenalectomy was higher in pregnant than in non-pregnant mice. There was a significant linear increase in survival during the first 5 days of pregnancy. Progesterone and prolactin both appeared to be involved in increasing the chance of survival in adrenalectomized pregnant mice. Adrenalectomy had no effect on the number of mice mating and ovulating. Adrenalectomized mice were apparently having normal cycles and 4 weeks after adrenalectomy they were able to mate and ovulate. Compensatory ovulation was seen in hemi-ovariectomized mice and was not abolished by adrenalectomy. Implantation was also unaffected by the operation.

Pituitary hormone control of implantation in the mouse.

In hypophysectomized pregnant mice replacement therapy designed to mimic the normal physiological situation showed that FSH in combination with either prolactin or LH, or prolactin plus LH, could initiate implantation in the absence of the pituitary gland. No pituitary hormone was by itself capable of achieving this result. The combination of prolactin with FSH gave better results than a combination of LH with FSH. Prolactin from sheep, cattle or rats was equally effective in combination with rat FSH in initiating implantation. In mice exhibiting suckling-induced delay of implantation this delay was terminated by injection of FSH. GH by itself or in conjunction with other hormones had no significant effect on implantation or on any of the other parameters associated with implantation that were measured. On the basis of these experimental results it is suggested that prolactin and LH are involved with progesterone production and FSH with oestrogen production, both of which are required for implantation in the mouse.

Effect on pregnancy and plasma progesterone of exogenous steroid maintenance in ovariectomised pregnant rabbits.

Pregnancy was maintained in ovariectomised does with 1 to 4 mg/day of exogenous progesterone with or without 0.2 microgram/day of estradiol. Progesterone doses were designed to give similar plasma progesterone levels in treated groups to those found in normal pregnancy, and were measured and compared with normals since this comparison does not appear to have been published previously. In normal pregnancy mean progesterone levels reached 10 ng/ml on day 7 and then plateaued at 14 ng/ml between day 10 and 20 before falling to very low levels at parturition. In treated groups progesterone levels reached 10 ng/ml on day 6 and remained between 10 and 13 ng/ml until day 20 before declining. The difference between treated and control plasma progesterone plateau levels was tested using the t-test and was found not be significant. The differences in progesterone levels between treated groups with or without estradiol, whether pregnant or not, were also not significant. Mean litter sizes (alive or dead) were not significantly different. However, fetal viability in the group maintained on progesterone alone was significantly lower than in the normal controls.

Further observations on hormonal support of pregnancy in the ovariectomized rabbit.

While the necessity for progesterone administration throughout pregnancy in the ovariectomized rabbit is not questioned, the roles of 20alpha-dihydroprogesterone and oestradiol are still in doubt. 20alpha-dihydroprogesterone was shown to be a weak inducer of implantation with less than one-tenth the potency of progesterone. The significance of its high level of production on the day after mating remains obscure. In combination with the earlier results of Kwun and Emmens (1974), further work with oestradiol suggests that at no stage is it clearly needed for successful maintenance of pregnancy. However, in low doses (0.125-0.2 mug/day prior to implantation, 0.2 rising to 1.6 mug, or remaining at 0.2 mug/day thereafter) it produced slight but sometimes significant improvements in implantation and foetal development percentages. Birth processes were abnormal if progesterone injections were continued beyond day 29. Foetuses were most frequently retained in utero or born dead after a somewhat prolonged pregnancy. The cessation of injections on day 29, whether or not a low dosage of 0.2 mug of oestradiol per day were continued, resulted in 94-98% normal parturition, but the percentage of live births was still significantly below that of controls unless oestradiol was given.

Effects of estrogen and progesterone on uterine sialic acid in ovariectomized rats.

The effects of estradiol-17beta and progesterone on uterine sialic acid of ovariectomized rats have been examined. In contrast to a previous report, progesterone was found in two of three experiments of different design to increase uterine sialic acid concentration above that produced by estradiol-17beta alone; in the third experiment, it had no significant effect. This effect of progesterone was independent of the duration of treatment with exogenous hormones or of whether or not uterine luminal fluid was removed by blotting before assaying sialic acid. In a factorially designed experiment with four levels of estradiol-17beta and three of progesterone, a dose-response relationship was found between estradiol-17beta, but not progesterone, and uterine sialic acid concentration. It is concluded that, in some circumstances, estrogen and progesterone can act synergistically to increase uterine sialic acid concentration.

Antifertility agents.

PIP: The emphasis in this review is upon agents influencing postcoital events. Drugs discussed exert their effects upon the central nervous system, peripheral hormonal organs, fertilization, tubal transport, blastocyst implantation, and the zygote. The relationships between estrogenic, antiestrogenic, and antifertility activities of the drugs are discussed. The peculiarities of the nonsteroidal compounds may be due to the period of time they occupy receptors in the uterus or other target organs. Special attention is given to stilbene and bibenzyl derivatives; basic ether derivatives of DMS and related compounds; and U-11,100A, U-11,555A, and similar compounds.^ieng