Outreach &Education Core (Core C) Background In our previous grant cycles, this Center has assembled a considerable amount of valuable information regarding the genotypes and phenotypes of GnRH deficient patients including those with isolated GnRH deficiency both with anosmia, i.e. Kallmann Syndrome (KS) and with normosmic Idiopathic Hypogonadotropic Hypogonadism (nIHH). We have also: a) described novel clinical variations on this theme such as reversal of GnRH deficiency (PI 9) and adult onset variety (Nachtigall et. al. N Engl J Med 1997 &P42); b) documented that digenicity/oligogenicity is evident in a significant proportion of cases (PI 4, P45); c) begun exploring the role of mutations in these genes in more common reproductive disorders such as precocious puberty (P22), and hypothalamic amenorrhea (P46). Thus, through the incremental work of this Center and other investigators around the world, the collective understanding of the genetics of this condition has advanced considerably. From completely lacking a genetic explanation in 1990 to now accounting for 33% of patients having an identifiable genetic defect (cf. Introductory Overview/ Fig 1 page 93) this striking change represents a rather remarkable gain in information. These findings have not only propelled several areas of neuroendocrine research but have also made significant contributions to the care and genetic counseling of patients and families with these disorders. As a direct consequence of this rapid progress, we have now amassed the world?s largest and most thoroughly phenotyped and genotyped cohort of patients with GnRH deficiency and their family members (cf. Introductory Overview, pg. 93). Over 400 of these probands now undergone complete sequencing of all known genes that are causative for this disease (publication P45). In addition, we also have assembled DNA samples from large and growing populations of the more common reproductive conditions in which some abnormality of GnRH secretion has been documented as described in the introductory Overview

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1-DSR-L)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Sidhoum, Valerie F; Chan, Yee-Ming; Lippincott, Margaret F et al. (2014) Reversal and relapse of hypogonadotropic hypogonadism: resilience and fragility of the reproductive neuroendocrine system. J Clin Endocrinol Metab 99:861-70
Martin, Cecilia; Navarro, VĂ­ctor M; Simavli, Serap et al. (2014) Leptin-responsive GABAergic neurons regulate fertility through pathways that result in reduced kisspeptinergic tone. J Neurosci 34:6047-56
Ahow, Maryse; Min, Le; Pampillo, Macarena et al. (2014) KISS1R signals independently of G?q/11 and triggers LH secretion via the ?-arrestin pathway in the male mouse. Endocrinology 155:4433-46
Thompson, Iain R; Kaiser, Ursula B (2014) GnRH pulse frequency-dependent differential regulation of LH and FSH gene expression. Mol Cell Endocrinol 385:28-35
Noel, Sekoni D; Abreu, Ana Paula; Xu, Shuyun et al. (2014) TACR3 mutations disrupt NK3R function through distinct mechanisms in GnRH-deficient patients. FASEB J 28:1924-37
Min, Le; Soltis, Kathleen; Reis, Ana Claudia S et al. (2014) Dynamic kisspeptin receptor trafficking modulates kisspeptin-mediated calcium signaling. Mol Endocrinol 28:16-27
Salian-Mehta, S; Xu, M; Knox, A J et al. (2014) Functional consequences of AXL sequence variants in hypogonadotropic hypogonadism. J Clin Endocrinol Metab 99:1452-60
Kaiser, Ursula B (2014) Editorial: advances in neuroscience: the BRAIN initiative and implications for neuroendocrinology. Mol Endocrinol 28:1589-91
Macedo, Delanie B; Abreu, Ana Paula; Reis, Ana Claudia S et al. (2014) Central precocious puberty that appears to be sporadic caused by paternally inherited mutations in the imprinted gene makorin ring finger 3. J Clin Endocrinol Metab 99:E1097-103
Beneduzzi, Daiane; Trarbach, Ericka B; Min, Le et al. (2014) Role of gonadotropin-releasing hormone receptor mutations in patients with a wide spectrum of pubertal delay. Fertil Steril 102:838-846.e2

Showing the most recent 10 out of 101 publications