This research proposal plans to investigate the physiology of GnRH in the normal human menstrual cycle; to explore the range of pathophysiologic defects of GnRH in anovulatory infertility; to attempt to induce ovulation in ovulatory disorders with pulsatile GnRH; and to explore a GnRH antagonist across the human menstrual cycle. In continuation of our previous studies on the human menstrual cycle we plan to complete the study of the normal range of frequency and amplitude changes of GnRH-induced gonadotropin pulsations which occur in 60 normal females throughout the course of an ovulatory menstrual cycle. In addition, we will document the spectrum and nature of the abnormalities of GnRH which exist in specific subsets of anovulatory infertility including, a) hypothalamic amenorrhea, b) hyperprolactinemia in the absence of a pituitary tumor, c) polycystic ovarian disease, and d) inadequate luteal phase. Following a comprehensive baseline assessment of their GnRH program we plan to induce ovulation in them using intravenous administration of GnRH at hourly intervals throughout the follicular phase at a dose of 25 ng/kg. When ovulation has been documented by ultrasound, estradiols, and basal body temperature charts, the frequency of GnRH administration will be progressively slowed at a schedule compatible with that observed in the normal human menstrual cycle. Finally, a GnRH antagonist will be explored in three phases of the menstrual cycle in a log order of doses and the optimized dose used at six separate phases of the menstrual cycle to induce a temporary blockade of GnRH function and employ this physiologic probe to examine intra- and inter-cycle relationships mediated by GnRH's induction of pulsatile gonadotropin release.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD015080-07
Application #
3312966
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1987-04-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Hall, Janet E; Sullivan, Jason P; Richardson, Gary S (2005) Brief wake episodes modulate sleep-inhibited luteinizing hormone secretion in the early follicular phase. J Clin Endocrinol Metab 90:2050-5
Lavoie, H B; Martin, K A; Taylor, E et al. (1998) Exaggerated free alpha-subunit levels during pulsatile gonadotropin-releasing hormone replacement in women with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 83:241-7
Hayes, F J; Taylor, A E; Martin, K A et al. (1998) Use of a gonadotropin-releasing hormone antagonist as a physiologic probe in polycystic ovary syndrome: assessment of neuroendocrine and androgen dynamics. J Clin Endocrinol Metab 83:2343-9
Hayes, F J; Hall, J E; Boepple, P A et al. (1998) Clinical review 96: Differential control of gonadotropin secretion in the human: endocrine role of inhibin. J Clin Endocrinol Metab 83:1835-41
Martin, K A; Welt, C K; Taylor, A E et al. (1998) Is GnRH reduced at the midcycle surge in the human? Evidence from a GnRH-deficient model. Neuroendocrinology 67:363-9
Welt, C K; Martin, K A; Taylor, A E et al. (1997) Frequency modulation of follicle-stimulating hormone (FSH) during the luteal-follicular transition: evidence for FSH control of inhibin B in normal women. J Clin Endocrinol Metab 82:2645-52
Khoury, R H; Wang, Q F; Crowley Jr, W F et al. (1995) Serum follistatin levels in women: evidence against an endocrine function of ovarian follistatin. J Clin Endocrinol Metab 80:1361-8
Taylor, A E; Whitney, H; Hall, J E et al. (1995) Midcycle levels of sex steroids are sufficient to recreate the follicle-stimulating hormone but not the luteinizing hormone midcycle surge: evidence for the contribution of other ovarian factors to the surge in normal women. J Clin Endocrinol Metab 80:1541-7
Hall, J E; Taylor, A E; Martin, K A et al. (1994) Decreased release of gonadotropin-releasing hormone during the preovulatory midcycle luteinizing hormone surge in normal women. Proc Natl Acad Sci U S A 91:6894-8
Taylor, A E; Khoury, R H; Crowley Jr, W F (1994) A comparison of 13 different immunometric assay kits for gonadotropins: implications for clinical investigation. J Clin Endocrinol Metab 79:240-7

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