Abstract

The objective of this application is to understand the molecular mechanisms involved in the hormonal regulation and tissue-specific expression of the GnRHR gene.
The specific aims i nclude 1) determine the physiologic regulation of GnRHR gene transcription and mRNA stability in vivo and in vitro by GnRH, activin, and estrogen; 2) identify and characterize functional cis-DNA elements of the mouse GnRHR gene and identify factors which interact with these elements; 3) identify and characterize cis-DNA elements and factors that mediate GnRH responsiveness; 4) use the 5'-flanking region of the GnRHR gene to direct oncogene expression to the pituitary in an attempt to develop LH- and FSH-producing cell lines; and 5) use GnRHR transgenes to study the regulation by GnRH, activin, and steroid hormones.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD019938-13
Application #
2857416
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
De Paolo, Louis V
Project Start
1990-08-01
Project End
2002-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
13
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Stamatiades, George A; Kaiser, Ursula B (2018) Gonadotropin regulation by pulsatile GnRH: Signaling and gene expression. Mol Cell Endocrinol 463:131-141
Ross, Rachel A; Leon, Silvia; Madara, Joseph C et al. (2018) PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse. Elife 7:
Zheng, Junjie; Mao, Jiangfeng; Xu, Hongli et al. (2017) Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial. J Clin Endocrinol Metab 102:2291-2300
Ercan, Altan; Kohrt, Wendy M; Cui, Jing et al. (2017) Estrogens regulate glycosylation of IgG in women and men. JCI Insight 2:e89703
Bi, Wenya Linda; Greenwald, Noah F; Ramkissoon, Shakti H et al. (2017) Clinical Identification of Oncogenic Drivers and Copy-Number Alterations in Pituitary Tumors. Endocrinology 158:2284-2291
Mao, Jiang-Feng; Liu, Zhao-Xiang; Nie, Min et al. (2017) Pulsatile gonadotropin-releasing hormone therapy is associated with earlier spermatogenesis compared to combined gonadotropin therapy in patients with congenital hypogonadotropic hypogonadism. Asian J Androl 19:680-685
Maguire, Caroline A; Song, Yong Bhum; Wu, Min et al. (2017) Tac1 Signaling Is Required for Sexual Maturation and Responsiveness of GnRH Neurons to Kisspeptin in the Male Mouse. Endocrinology 158:2319-2329
Lee, Hyunju; Hodi, F Stephen; Giobbie-Hurder, Anita et al. (2017) Characterization of Thyroid Disorders in Patients Receiving Immune Checkpoint Inhibition Therapy. Cancer Immunol Res 5:1133-1140
Min, Le; Nie, Min; Zhang, Anna et al. (2016) Computational Analysis of Missense Variants of G Protein-Coupled Receptors Involved in the Neuroendocrine Regulation of Reproduction. Neuroendocrinology 103:230-9
Abreu, Ana Paula; Kaiser, Ursula B (2016) Pubertal development and regulation. Lancet Diabetes Endocrinol 4:254-264

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