The mechanisms by which lactation and malnutrition inhibit ovulation are important medically and have significant demographic implications. The experiments proposed here are the first to utilize the ovariectomized rat as an animal model for studying the independent and synergistic effects of chronic undernutrition and suckling on the modulation of prolactin and gonadotropin release during lactation. Experiment 1 will examine the effects of litter size and dietary restriction on the control of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin release from the pituitary. This experiment will utilize a 3 x 3 factorial design with dietary intake (ad libitum, 85% ad libitum, and 70% ad libitum) and litter size (2, 5, and 8 pups) as the main factors. It is hypothesized that both dietary restriction and increased litter size will independently and synergistically influence circulating LH, FSH and prolactin concentrations. Furthermore, we expect both main factors to independently and interactively result in depressed responsiveness to gonadotropin releasing hormone (GnRH) as measured by plasma LH and FSH responses to GnRH challenge. Maternal and pup behavior will also be documented and used in regression analyses to predict plasma hormone concentrations. Experiment 2 will study the effect of food supplementation on gonadotropin release and pituitary responsiveness to GnRH as well as prolactin concentrations. We hypothesize that LH, FSH and prolactin concentrations will be increased in food-restricted lactating animals when refed. Again, the effects of dietary regimen on dam and litter behavior will be assessed. Experiment 3 will examine the effect of an opioid antagonist (naloxone) or prolactin inhibiting factor (bromocriptine) on plasma LH concentrations in lactating ad libitum-fed and food-restricted rats. Both well -fed and chronically undernourished, ovariectomized lactating rats will be treated with either naloxone, bromocriptine, naloxone and bromocriptine, or saline. The effect of nutritional status and drug treatment on plasma LH concentrations and responsiveness to GnRH will be determined in early (d 10) and peak (d 14) lactation. It is hypothesized that endogenous opioids contribute more to hypothalamic suppression during malnutrition than does the dopaminergic pathway. In summary, these experiments will provide incisive information concerning the physiological mechanisms by which lactation, undernutrition and suckling. characteristics interact and influence the hypothalamic-pituitary-ovarian axis.
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