Female Reproductive System: Neuroendocrine control and effects of stress

Abstract

Understanding regulation of the ovarian cycle is important for control of fertility in animals, to elucidate and treat cases of infertility in women, to adapt anticonception strategies to personal needs, to treat behavioral alterations, such as premenstrual syndrome, and to promote adequate therapies for different female pathologies which are subjected to interference by variations in hormone titers during the reproductive cycles or ovarianquiescence. The hormonal variations that normally occur during the estrous cycle make the research on female animals more difficult, and consequently, most of the published investigations were performed on males. In Brazil there is only a small number of researchers in this field, including the ones which have joined forces in this project to study mechanisms of control in the release of reproductive hormones and on the effects of stress during there productive phase of life. The aims of this work are to investigate: 1) the central control of the reproductive process in cycling and in ovariectomized rats with or without hormone replacement. We will focus the research on the function of several central neuromediators (noradrenaline, angiotensin II, neuropeptide Y, nitric oxide) in the secretion of hormones related to reproduction, as well as on the funetion of ovarian steroids on the release of these neuromediators; 2) how sexual hormones can alter stress responses, and 3) how stress can alter reproductive functions. The following techniques will be used in this project- vaginal smears to study estrous cycles, ovariectomv followed or not by hormonal replacement (estrogen and progesterone) to study the role of ovarian steroids on the responses observed and to compare them to those observed in cycling rats, electrolytic lesions to study the role of cerebral nuclei in the control of hypothalamus-pituitary-ovary function, juqular cannulation to collect serial samples for investigation of hormonal responses to different physiological challenges, radioimmunoassay to measure several hormones, catecholamines measurements by HPLC in dyalisate as well as cerebral tissue, punch and microdialysis of cerebral nuclei to measure content and secretion of hormones and neurotransmitters in cerebral nuclei, activity measurements of nitric oxide synthase to analyze nitric oxide action, liquid or in situ hibridization to evaluate expression of genes coding for NPY and Ali receptors, neonatal stimulation to study its effects on the reproductive performance during adulthood, estimation of the number of brain cells to study stress-evoked morphologic alterations in cerebral nuclei, and behavioral computerized recording to evaluate the effects of stress and sexual hormones on behavior. (AU)