This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Gonadotropin-releasing hormone is secreted in a pulsatile fashion and is transported through the hypothalamic-hypophyseal portal circulation to the anterior pituitary where it interacts with specific receptors on gonadotropes to effect the pulsatile secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Although GnRH secretion cannot be measured directly in the human, there is a one-to-one relationship between pulsatile GnRH and pulsatile gonadotropin secretion. Significant investigative attention has focussed on the identification and characterization of LH and FSH pulses to provide a useful reflection of GnRH neuronal activity. Within this context, inferences have been made about CNS/hypothalamic GnRH activity in a number of pathophysiologic situations such as polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA). Although there has been a general consensus that the frequency with which the hypothalamus discharges GnRH is slowed in the setting of hypothalamic amenorrhea, characterization of pulsatile GnRH secretion in women with the polycystic ovarian syndrome is controversial. Whereas some investigators have documented a substantial increase in the frequency of pulsatile GnRH secretion in women with PCOS, others have failed to observe any difference between normal women and those with PCOS. Recently, it has been suggested that these conflicting results may reflect alterations in BMI, with lower and higher BMIs associating with higher and lower frequencies of GnRH secretion, respectively. In the current study, we will study women with PCOS and HA across a wide range of BMIs in an effort to confirm or refute the hypothesis that BMI associates with alterations in GnRH pulse generator activity in women with PCOS but not with hypothalamic amenorrhea. These results in women with PCOS and HA will be compared to those obtained in normal women studied under identical circumstances in companion protocols (WSE-025 and WSE-030).
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