MON-018 Fertility Rates in Rats Characterized by Increased Hypothalamic CRH Secretion

Certain strains of rats are characterized by hyperactive Hypothalamic-Pituitary-Adrenal axis responses to stress, increased hypothalamic Corticotropin-Releasing Hormone (CRH) production and decreased fertility rates. Activation of the HPA-axis and CRH secretion has been associated with suppression of the Hypothalamic-Pituitary-Ovarian axis primarily as a result of glucocorticoids. Here we examined the hypothesis that Fischer rats have decreased fertility rates because of hypothalamic CRH hypersecretion. Antalarmin, a CRH receptor type 1 antagonist, is known to suppress adrenocorticotropin hormone secretion and other CRH receptor type 1-mediated responses. Adult female Fischer rats were injected with antalarmin or placebo, twice a day, for 16 days. Mating was evidenced by the presence of spermatozoa in the vaginal smear performed every morning. After 16 days, 20% of rats (20%) treated with placebo became pregnant and 55% rats treated with antalarmin became pregnant. We have previously reported that administration of antalarmin after the first day of pregnancy does not affect blastocyst implantation in Fischer rats. Our data suggest that antalarmin improves fertility rates in Fischer rats by antagonizing the direct antireproductive role of hypothalamic CRH.