TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction

被引：660

作者：

Topaloglu, A. Kemal ^{[1
]}

Reimann, Frank ^{[2
,3
]}

Guclu, Metin ^{[4
]}

Yalin, Ayse Serap ^{[5
]}

Kotan, L. Damla ^{[6
]}

Porter, Keith M. ^{[7
]}

Serin, Ayse ^{[6
]}

Mungan, Neslihan O. ^{[1
]}

Cook, Joshua R. ^{[7
]}

Ozbek, Mehmet N. ^{[1
]}

Imamoglu, Sazi ^{[4
]}

Akalin, N. Sema ^{[5
]}

Yuksel, Bilgin ^{[1
]}

O'Rahilly, Stephen ^{[7
]}

Semple, Robert K. ^{[7
]}

机构：

[1] Cukurova Univ, Fac Med, Dept Pediat Endocrinol & Metab, TR-01330 Adana, Turkey

[2] Univ Cambridge, Cambridge Inst Med Res, Addenbrookes Hosp, Cambridge CB2 0XY, England

[3] Univ Cambridge, Dept Clin Biochem, Addenbrookes Hosp, Cambridge CB2 0XY, England

[4] Uludag Univ, Fac Med, Dept Endocrinol & Metab, TR-16059 Bursa, Turkey

[5] Marmara Univ, Fac Med, Dept Endocrinol & Metab, TR-24722 Istanbul, Turkey

[6] Cukurova Univ, Fac Med, Dept Forens Med, TR-01330 Adana, Turkey

[7] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp, Cambridge CB2 0QQ, England

来源：

NATURE GENETICS | 2009年 / 41卷 / 03期

基金：

英国惠康基金;

关键词：

ARCUATE NUCLEUS; TACHYKININ RECEPTORS; MORPHOLOGIC EVIDENCE; RAT HYPOTHALAMUS; HORMONE NEURONS; EXPRESSION; DYNORPHIN; MICE; KISSPEPTIN; DEFICIENCY;

D O I：

10.1038/ng.306

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：354 / 358

页数：5

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