Kisspeptin and neurokinin B are both critical gatekeepers for reproductive maturation but there is still much to learn about how these neuropeptides stimulate GnRH secretion. This grant will anchor a collaboration between two investigators uniquely positioned to study the physiology of these peptides in non-human primates and humans in vivo. In the male monkey, the contributions of kisspeptin and NKB to GnRH secretion will be explored across puberty using novel assays and receptor agonists and antagonists. In the adult human male, exogenous kisspeptin administration to patients with idiopathic hypogonadotropic hypogonadism (IHH) will be assessed as a predictive tool for spontaneous recovery of GnRH pulsatile secretion. In the adolescent human male, exogenous kisspeptin will be explored as a diagnostic tool to distinguish between constitutional delay of puberty (CDP) and IHH. By focusing on the pubertal transition, and incorporating normal and pathophysiologic states, this grant will develop insights into reproductive maturation and develop diagnostic tools for pubertal disorders.
Pubertal development in childhood remains poorly understood: some children develop too early, others too late or not at all. This research study investigates how the hormones kisspeptin and neurokinin B work in the brain to bring about puberty. This study will also determine if kisspeptin can be used in the clinic to help predict outcomes for children and adults who have delayed reproductive development.
|Teive, Hélio Afonso Ghizoni; Camargo, Carlos Henrique F; Sato, Mario Teruo et al. (2018) Different Cerebellar Ataxia Phenotypes Associated with Mutations of the PNPLA6 Gene in Brazilian Patients with Recessive Ataxias. Cerebellum 17:380-385|
|Lippincott, Margaret F; Nguyen, Kiana; Delaney, Angela et al. (2018) Assessing Sex Steroid Influence on Kisspeptin Responsiveness in Idiopathic Hypogonadotropic Hypogonadism. J Endocr Soc 2:1293-1305|
|Terasawa, Ei; Garcia, James P; Seminara, Stephanie B et al. (2018) Role of Kisspeptin and Neurokinin B in Puberty in Female Non-Human Primates. Front Endocrinol (Lausanne) 9:148|
|Garcia, James P; Keen, Kim L; Kenealy, Brian P et al. (2018) Role of Kisspeptin and Neurokinin B Signaling in Male Rhesus Monkey Puberty. Endocrinology 159:3048-3060|
|Shahab, Muhammad; Lippincott, Margaret; Chan, Yee-Ming et al. (2018) Discordance in the Dependence on Kisspeptin Signaling in Mini Puberty vs Adolescent Puberty: Human Genetic Evidence. J Clin Endocrinol Metab 103:1273-1276|
|Chan, Yee-Ming; Lippincott, Margaret F; Kusa, Temitope O et al. (2018) Divergent responses to kisspeptin in children with delayed puberty. JCI Insight 3:|
|Shaw, Natalie D; Brand, Harrison; Kupchinsky, Zachary A et al. (2017) SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome. Nat Genet 49:238-248|
|Richards, Mary R; Plummer, Lacey; Chan, Yee-Ming et al. (2017) Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies. J Med Genet 54:19-25|
|Garcia, James P; Guerriero, Kathryn A; Keen, Kim L et al. (2017) Kisspeptin and Neurokinin B Signaling Network Underlies the Pubertal Increase in GnRH Release in Female Rhesus Monkeys. Endocrinology 158:3269-3280|
|Lippincott, Margaret F; Chan, Yee-Ming; Rivera Morales, Dianali et al. (2017) Continuous Kisspeptin Administration in Postmenopausal Women: Impact of Estradiol on Luteinizing Hormone Secretion. J Clin Endocrinol Metab 102:2091-2099|
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