It is the broad goal of this project to investigate the physiology of GnRH deficient male by using GnRH deficient males undergoing long-term administration of GnRH for induction of sexual maturation and normal men. By contrasting their responses to a variety of modulatory influences known to impact upon the hypothalamic- pituitary-gonadal-axis of the male, we will attempt to determine the site of action and relative contribution of testosterone and estradiol feedback upon the hypothalamic-pituitary-axis in the male. In addition, we will determine the role of physiologic variations in the interpulse interval and contour of the GnRH pulse upon the quantitative and qualitative nature of gonadotropin secretion in the male. Finally, we will measure inhibin levels by radioimmunoassay in GnRH-deficient men during induction of sexual maturation with GnRH and in adult males. These levels will be correlated with gonadal size, the onset of spermatogenesis, and FSH secretion. With the combined use of normal males with an intact and free- running hypothalamic-pituitary-gonadal axis and GnRH deficient men in whom the hypothalamic input can be experimentally defined, it should be possible to provide new and useful information in the physiology of GnRH in the human. Such information is a critical step for the understanding and definition of abnormalities of the male reproductive system.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD015788-09
Application #
3313242
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1981-07-01
Project End
1991-11-30
Budget Start
1990-07-01
Budget End
1991-11-30
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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Choi, Jin-Ho; Balasubramanian, Ravikumar; Lee, Phil H et al. (2015) Expanding the Spectrum of Founder Mutations Causing Isolated Gonadotropin-Releasing Hormone Deficiency. J Clin Endocrinol Metab 100:E1378-85
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Miraoui, Hichem; Dwyer, Andrew A; Sykiotis, Gerasimos P et al. (2013) Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet 92:725-43
Dwyer, Andrew A; Sykiotis, Gerasimos P; Hayes, Frances J et al. (2013) Trial of recombinant follicle-stimulating hormone pretreatment for GnRH-induced fertility in patients with congenital hypogonadotropic hypogonadism. J Clin Endocrinol Metab 98:E1790-5
Chew, Sheena; Balasubramanian, Ravikumar; Chan, Wai-Man et al. (2013) A novel syndrome caused by the E410K amino acid substitution in the neuronal ?-tubulin isotype 3. Brain 136:522-35
Costa-Barbosa, Flavia Amanda; Balasubramanian, Ravikumar; Keefe, Kimberly W et al. (2013) Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes. J Clin Endocrinol Metab 98:E943-53

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