The purpose of this project is to understand better the development of the endometrium and oocyte in women and to investigate the role of gonadal steroids in these processes. Studies evaluating ovarian function in women suggested that growth hormone (GH) may be an important mediator of follicular development, as its receptor is present in the granulosa cells of the developing follicle and in the corpus luteum, the estrogen and progesterone steroidogenic compartments. We also demonstrated that a complete fast for 72 hours during the mid-follicular phase does not disrupt folliculogenesis, ovulation, or menstrual cycle dynamics in normal weight women, suggesting that brief periods of undernutrition are not deleterious to reproductive function. Another study evaluated the effect of aging on reproductive function. FSH was increased, and inhibin decreased, in the luteal-follicular transition of women aged 40 - 50 years compared to those aged 20 - 30 years, but the incidence of abnormal endometrial biopsies was similar. These results suggest that follicular recruitment, but not luteal function or endometrial maturation, is disturbed in cycling women over 40 years old and may contribute to decreased fertility. The process of uterine remodeling that is so remarkable in the mammalian uterus is achieved through coordinated proliferation, differentiation and cell death. While the gonadal steroids estradiol and progesterone appear to be required for these organ-specific processes, the mechanism(s) by which these processes are regulated remain unclear. Potential mediators of estrogen action include IGF-1 and c-Myc, a transcription factor known to be induced by growth factors. We used a well-characterized in vivo ovariectomized mouse model to correlate sex steroid-induced proliferation with the induction of IGF-1 and c-Myc mRNA in the uterine endometrium. We have found that IGF-1 and c-Myc levels parallel each other and the estrogen-induced processes of differentiation in this model, suggesting that they are important to proliferation. The induction of IGF-1 by GH in other tissues prompted an evaluation of whether the GH receptor was present in the endometrium, based on the hypothesis that GH might act directly on the endometrium and so modulate estrogen effect. GH receptor was found to be present throughout the endometrium, but was not regulated by estradiol.
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