TY - JOUR
T1 - GLUT1-mediated glycolysis supports GnRH-induced secretion of luteinizing hormone from female gonadotropes
AU - Nicholas, Dequina A.
AU - Knight, Vashti S.
AU - Tonsfeldt, Karen J.
AU - Terasaka, Tomohiro
AU - Molinar-Inglis, Olivia
AU - Stephens, Shannon B.Z.
AU - Trejo, Jo Ann
AU - Kauffman, Alexander S.
AU - Mellon, Pamela L.
AU - Lawson, Mark A.
N1 - Funding Information:
This work was supported by the following sources: NIH grants P50 HD 012303 and R01 HD 082567 awarded to M.A.L. and P.L.M.; M. A. L. was also supported by R01 HD 091167. NIH grant K99 HD 092894 awarded to S.B.Z.S. NIH grant K99 HD 098330 awarded to D.A.N. NIH R25 GM 083275 awarded to M.A.L. NIH F32 HD 088060 awarded to S.B.Z.S. NIH F32 HD 090837 awarded to K.J.T., T32 HD 007203 partially supported S.B.Z.S. and K.J.T. D.A.N. is a UCSD IRACDA Fellow (K12 GM 068524) and a University of California President’s Postdoctoral Fellow.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The mechanisms mediating suppression of reproduction in response to decreased nutrient availability remain undefined, with studies suggesting regulation occurs within the hypothalamus, pituitary, or gonads. By manipulating glucose utilization and GLUT1 expression in a pituitary gonadotrope cell model and in primary gonadotropes, we show GLUT1-dependent stimulation of glycolysis, but not mitochondrial respiration, by the reproductive neuropeptide GnRH. GnRH stimulation increases gonadotrope GLUT1 expression and translocation to the extracellular membrane. Maximal secretion of the gonadotropin Luteinizing Hormone is supported by GLUT1 expression and activity, and GnRH-induced glycolysis is recapitulated in primary gonadotropes. GLUT1 expression increases in vivo during the GnRH-induced ovulatory LH surge and correlates with GnRHR. We conclude that the gonadotropes of the anterior pituitary sense glucose availability and integrate this status with input from the hypothalamus via GnRH receptor signaling to regulate reproductive hormone synthesis and secretion.
AB - The mechanisms mediating suppression of reproduction in response to decreased nutrient availability remain undefined, with studies suggesting regulation occurs within the hypothalamus, pituitary, or gonads. By manipulating glucose utilization and GLUT1 expression in a pituitary gonadotrope cell model and in primary gonadotropes, we show GLUT1-dependent stimulation of glycolysis, but not mitochondrial respiration, by the reproductive neuropeptide GnRH. GnRH stimulation increases gonadotrope GLUT1 expression and translocation to the extracellular membrane. Maximal secretion of the gonadotropin Luteinizing Hormone is supported by GLUT1 expression and activity, and GnRH-induced glycolysis is recapitulated in primary gonadotropes. GLUT1 expression increases in vivo during the GnRH-induced ovulatory LH surge and correlates with GnRHR. We conclude that the gonadotropes of the anterior pituitary sense glucose availability and integrate this status with input from the hypothalamus via GnRH receptor signaling to regulate reproductive hormone synthesis and secretion.
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U2 - 10.1038/s41598-020-69913-z
DO - 10.1038/s41598-020-69913-z
M3 - Article
C2 - 32747664
AN - SCOPUS:85088877797
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 13063
ER -