Abstract
Ionotropic glutamate receptors mediate most excitatory neurotransmission in the central nervous system by opening ion channels upon the binding of glutamate. Despite the essential roles of glutamate in the control of reproduction and anterior pituitary hormone secretion, there is a limited understanding of how glutamate receptors control ovulation. Here we reveal the function of the ionotropic glutamate receptor AMPA-1 (GRIA1) in ovulation. Based on a genome-wide association study in Bos taurus, we found that ovulation rate is influenced by a variation in the N-terminal leucine/ isoleucine/valine-binding protein (LIVBP) domain of GRIA1, in which serine is replaced by asparagine. GRIA1Asn has a weaker affinity to glutamate than GRIA1Ser, both in Xenopus oocytes and in the membrane fraction of bovine brain. This single amino acid substitution leads to the decreased release of gonadotropin-releasing hormone (GnRH) in immortalized hypothalamic GT1-7 cells. Cows with GRIA1Asn have a slower luteinizing hormone (LH) surge than cows with GRIA1Ser. In addition, cows with GRIA1Asn possess fewer immature ovarian follicles before superovulation and have a lower response to hormone treatment than cows with GRIA1Ser. Our work identified that GRIA1 is a critical mediator of ovulation and that GRIA1 might be a useful target for reproductive therapy.
| Original language | English |
|---|---|
| Article number | e13817 |
| Journal | PLoS One |
| Volume | 5 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2010 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Ionotropic glutamate receptor AMPA 1 is associated with ovulation rate. / Sugimoto, Mayumi; Sasaki, Shinji; Watanabe, Toshio; Nishimura, Shota; Ideta, Atsushi; Yamazaki, Maya; Matsuda, Keiko; Yuzaki, Michisuke; Sakimura, Kenji; Aoyagi, Yoshito; Sugimoto, Yoshikazu.
In: PLoS One, Vol. 5, No. 11, e13817, 2010.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ionotropic glutamate receptor AMPA 1 is associated with ovulation rate
AU - Sugimoto, Mayumi
AU - Sasaki, Shinji
AU - Watanabe, Toshio
AU - Nishimura, Shota
AU - Ideta, Atsushi
AU - Yamazaki, Maya
AU - Matsuda, Keiko
AU - Yuzaki, Michisuke
AU - Sakimura, Kenji
AU - Aoyagi, Yoshito
AU - Sugimoto, Yoshikazu
PY - 2010
Y1 - 2010
N2 - Ionotropic glutamate receptors mediate most excitatory neurotransmission in the central nervous system by opening ion channels upon the binding of glutamate. Despite the essential roles of glutamate in the control of reproduction and anterior pituitary hormone secretion, there is a limited understanding of how glutamate receptors control ovulation. Here we reveal the function of the ionotropic glutamate receptor AMPA-1 (GRIA1) in ovulation. Based on a genome-wide association study in Bos taurus, we found that ovulation rate is influenced by a variation in the N-terminal leucine/ isoleucine/valine-binding protein (LIVBP) domain of GRIA1, in which serine is replaced by asparagine. GRIA1Asn has a weaker affinity to glutamate than GRIA1Ser, both in Xenopus oocytes and in the membrane fraction of bovine brain. This single amino acid substitution leads to the decreased release of gonadotropin-releasing hormone (GnRH) in immortalized hypothalamic GT1-7 cells. Cows with GRIA1Asn have a slower luteinizing hormone (LH) surge than cows with GRIA1Ser. In addition, cows with GRIA1Asn possess fewer immature ovarian follicles before superovulation and have a lower response to hormone treatment than cows with GRIA1Ser. Our work identified that GRIA1 is a critical mediator of ovulation and that GRIA1 might be a useful target for reproductive therapy.
AB - Ionotropic glutamate receptors mediate most excitatory neurotransmission in the central nervous system by opening ion channels upon the binding of glutamate. Despite the essential roles of glutamate in the control of reproduction and anterior pituitary hormone secretion, there is a limited understanding of how glutamate receptors control ovulation. Here we reveal the function of the ionotropic glutamate receptor AMPA-1 (GRIA1) in ovulation. Based on a genome-wide association study in Bos taurus, we found that ovulation rate is influenced by a variation in the N-terminal leucine/ isoleucine/valine-binding protein (LIVBP) domain of GRIA1, in which serine is replaced by asparagine. GRIA1Asn has a weaker affinity to glutamate than GRIA1Ser, both in Xenopus oocytes and in the membrane fraction of bovine brain. This single amino acid substitution leads to the decreased release of gonadotropin-releasing hormone (GnRH) in immortalized hypothalamic GT1-7 cells. Cows with GRIA1Asn have a slower luteinizing hormone (LH) surge than cows with GRIA1Ser. In addition, cows with GRIA1Asn possess fewer immature ovarian follicles before superovulation and have a lower response to hormone treatment than cows with GRIA1Ser. Our work identified that GRIA1 is a critical mediator of ovulation and that GRIA1 might be a useful target for reproductive therapy.
UR - http://www.scopus.com/inward/record.url?scp=78149479993&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78149479993&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0013817
DO - 10.1371/journal.pone.0013817
M3 - Article
C2 - 21072200
AN - SCOPUS:78149479993
VL - 5
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 11
M1 - e13817
ER -