description) This application for the Harvard-wide Specialized Center for Reproduction proposes to bring the neuroendocrine and gonadal control of reproduction in the male. Two of the component of reproduction while the other two will explore the gonadal level as Leydig cell control of steroidogenesis. In Project I, will employ tandem phenotyping and genotyping approaches in patients with idiopathic hypogonadotropic hypogonadism (IHH). This is a human model in which a series of genetic defects result in failure of the neuroendocrine component of sexual maturation. In Project II, Dr. Ursula Kaiser will explore the GnRH of gonadotropic genes using LH-T2 cells which are of gonadotrope origin. In Inhibiting Substance (MIS) upon steroidogenesis using the CYP17 gene as well MIS receptor. In addition, she will chart the developmental expression of this receptor and correlate it with steroidogenesis. In Project IV, Dr. Joel Habener will continue his explorations of the role of cAMP-activated pathways of alternative splicing of the gene encoding of the transcription factor, CREB. He will also explore the role of pituitary adenyl cyclase activating peptide; PACAP, and its alternatively spliced type 1 receptor in the autocrine control of spermatogenesis.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZHD1-DRG-D (U5))
Program Officer
Leppert, Phyllis C
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Massachusetts General Hospital
United States
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Crowley, William F; Balasubramanian, Ravi (2017) MicroRNA-7a2 suppression causes hypogonadotropism and uncovers signaling pathways in gonadotropes. J Clin Invest 127:796-797
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
Abreu, Ana Paula; Kaiser, Ursula B (2016) Pubertal development and regulation. Lancet Diabetes Endocrinol 4:254-264
Simavli, Serap; Abreu, Ana Paula; Kwaan, Mary R et al. (2016) Candidate gene analysis in a case of congenital absence of the endometrium. Fertil Res Pract 2:3
Stamou, M I; Cox, K H; Crowley Jr, William F (2016) Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the ""-Omics"" Era. Endocr Rev 2016:4-22
Cox, Kimberly H (2016) A Bisphenol by Any Other Name... Endocrinology 157:449-51
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; Macedo, Delanie B; Brito, Vinicius N et al. (2015) A new pathway in the control of the initiation of puberty: the MKRN3 gene. J Mol Endocrinol 54:R131-9
Babwah, Andy V; Navarro, VĂ­ctor M; Ahow, Maryse et al. (2015) GnRH Neuron-Specific Ablation of G?q/11 Results in Only Partial Inactivation of the Neuroendocrine-Reproductive Axis in Both Male and Female Mice: In Vivo Evidence for Kiss1r-Coupled G?q/11-Independent GnRH Secretion. J Neurosci 35:12903-16
Cox, Kimberly H (2015) A Kiss and a PRomise. Endocrinology 156:3063-5

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