HORMONAL CORRELATES OF PSYCHOGENIC PREGNANCY BLOCKS

Abstract

Various psychological stressors have adverse effects upon the first period of pregnancy in humans and other mammals, however the underlying hormonal mechanisms are not established. A review of previous research suggests that the hormones normally associated with stress, the adrenal corticosteroids, are not important in the mediation of this effect. This thesis examined the roles of the primary gonadal hormones, progesterone and estrogen, in stress-induced pregnancy blocks. Experiment 1 established a restraint stress procedure as a reliable paradigm for the examination of stress effects in pregnancy in an animal model. Restrained females produced significantly fewer litters than did controls. Experiments 2 to 4 were designed to evaluate the contribution of progesterone to stress-induced pregnancy blocks. Experiment 2 replicated the restraint effect in two strains of mice, and demonstrated that daily administration of 500 υg progesterone will reverse this effect in HS but not C57 mice. Experiment 3 demonstrated that exposure to a predator will also block pregnancy in C57 mice, although this effect was not consistent for the HS strain. This pregnancy block in C57 mice can be counteracted with concomitant progesterone administration. Experiment 4 showed that metyrapone, a compound which prevents the conversion of progesterone to corticosterone, was also partially effective in maintaining pregnancy under stressful circumstances. Experiments 5 to 7 were designed to assess the contribution of estrogen in pregnancy blocks caused by stress. In Experiment 5, the dose-response curve for unmodified 17β-estradiol was examined. Daily dosages of 0.333 υg and greater completely blocked pregnancy, that of 0.111 υg did so in the majority of females, while lesser dosages had little apparent affect. For comparison, the dose-response curve for estradiol 17β-benzoate was determined in Experiment 6. Results were very similar to those for 17β-estradiol in that pregnancy was completely blocked at daily dosages of 0.333 υg and greater, and there were only two completed pregnancies at a daily dosages of 0.111 υg, while females receiving lower doses were indistinguishable from controls. Given that estrogen is such a potent blocker of pregnancy, it is conceivable that if stress resulted in even minute increases in the endogenous estrogen levels, that pregnancy would fail. Experiment 7 demonstrated that daily administration of an antibody to estrogen will reverse a stress-induced pregnancy block. Experiment 8 shows direct measures, obtained via radioimmunoassay, of corticosterone, progesterone and estradiol in pregnant animals who were stressed or not. All three of these steroids were significantly elevated in the stressed animals. These results of this thesis suggest that estrogenic action may mediate stress-induced pregnancy blocks, and that estrogen may serve as a "stress hormone".