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Neuroendocrine control of female reproductive function by the activin receptor ALK7
Author(s) -
SandovalGuzmán Tatiana,
Göngrich Christina,
Moliner Annalena,
Guo Tingqing,
Wu Haiya,
Broberger Christian,
Ibáñez Carlos F.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-199059
Subject(s) - endocrinology , medicine , biology , knockout mouse , arcuate nucleus , activin receptor , hypothalamus , polycystic ovary , receptor , ovary , gonadotropic cell , regulator , luteinizing hormone , hormone , gene , insulin resistance , genetics , obesity
Activins are critical components of the signaling network that controls female reproduction. However, their roles in hypothalamus, and the specific functions of their different receptors, have not been elucidated. Here, we investigated the expression and function of the activin receptor ALK7 in the female reproductive axis using Alk7 ‐knockout mice. ALK7 was found in subsets of SF1‐expressing granulosa cells in the ovary, FSH gonadotrophs in the pituitary, and NPY‐expressing neurons in the arcuate nucleus of the hypothalamus. Alk7 ‐knockout females showed delayed onset of puberty and abnormal estrous cyclicity, had abnormal diestrous levels of FSH and LH in serum, and their ovaries showed premature depletion of follicles, oocyte degeneration, and impaired responses to exogenous gonadotropins. In the arcuate nucleus, mutant mice showed reduced expression of Npy mRNA and lower numbers of Npy ‐expressing neurons than wild‐type controls. Alk7 knockouts showed a selective loss of arcuate NPY/AgRP innervation in the medial preoptic area, a key central regulator of reproduction. These results indicate that ALK7 is an important regulator of female reproductive function and reveal a new role for activin signaling in the control of hypothalamic gene expression and wiring. Alk7 gene variants may contribute to female reproductive disorders in humans, such as polycystic ovary syndrome.—Sandoval‐Guzmán, T., Göngrich, C., Moliner, A., Guo, T., Wu, H., Broberger, C., Ibáñez, C. F. Neuroendocrine control of female reproductive function by the activin receptor ALK7. FASEB J. 26, 4966–4976 (2012). www.fasebj.org