TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction
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Date
2009-03
Authors
Topaloğlu, Ali Kemal
Reimann, Frank
Yalın, Ayşe Serap
Kotan, Leman Damla
Porter, Keith
Serin, Ayşe
Mungan, Neslihan Önenli
Cook, Joshua R.
Özbek, Mehmet Nuri
Akalın, Nefise Sema
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Research
Abstract
The timely secretion of gonadal sex steroids is essential for the initiation of puberty, the postpubertal maintenance of secondary sexual characteristics and the normal perinatal development of male external genitalia. Normal gonadal steroid production requires the actions of the pituitary-derived gonadotropins, luteinizing hormone and follicle-stimulating hormone. We report four human pedigrees with severe congenital gonadotropin deficiency and pubertal failure in which all affected individuals are homozygous for loss-of-function mutations in TAC3 (encoding Neurokinin B) or its receptor TACR3 (encoding NK3R). Neurokinin B, a member of the substance P-related tachykinin family, is known to be highly expressed in hypothalamic neurons that also express kisspeptin(1), a recently identified regulator of gonadotropin-releasing hormone secretion(2). These findings implicate Neurokinin B as a critical central regulator of human gonadal function and suggest new approaches to the pharmacological control of human reproduction and sex hormone-related diseases.
Description
Keywords
Arcuate nucleus, Tachykinin receptors, Morphologic evidence, Rat hypothalamus, Hormone neurons, Expression, Dynorphin, Mice, Kisspeptin, Deficiency, Genetics & heredity
Citation
Topaloglu, A. K. vd. (2009). " TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction ". Nature Genetics, 41(3), 354-358.