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Hindbrain lactate regulates preoptic gonadotropin-releasing hormone (GnRH) neuron GnRH-I protein but not AMPK responses to hypoglycemia in the steroid-primed ovariectomized female rat.
- Source :
-
Neuroscience [Neuroscience] 2015 Jul 09; Vol. 298, pp. 467-74. Date of Electronic Publication: 2015 Apr 28. - Publication Year :
- 2015
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Abstract
- Steroid positive-feedback activation of the gonadotropin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) neuroendocrine axis propagates the pre ovulatory LH surge, a crucial component of female reproduction. Our work shows that this key event is restrained by inhibitory metabolic input from hindbrain A2 noradrenergic neurons. GnRH neurons express the ultra-sensitive energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK); here, we investigated the hypothesis that GnRH nerve cell AMPK and peptide neurotransmitter responses to insulin-induced hypoglycemia are controlled by hindbrain lack of the oxidizable glycolytic end-product L-lactate. Data show that hypoglycemic inhibition of LH release in steroid-primed ovariectomized female rats was reversed by coincident caudal hindbrain lactate infusion. Western blot analyses of laser-microdissected A2 neurons demonstrate hypoglycemic augmentation [Fos, estrogen receptor-beta (ER-β), phosphoAMPK (pAMPK)] and inhibition (dopamine-beta-hydroxylase, GLUT3, MCT2) of protein expression in these cells, responses that were normalized by insulin plus lactate treatment. Hypoglycemia diminished rostral preoptic GnRH nerve cell GnRH-I protein and pAMPK content; the former, but not the latter response was reversed by lactate. Results implicate caudal hindbrain lactoprivic signaling in hypoglycemia-induced suppression of the LH surge, demonstrating that lactate repletion of that site reverses decrements in A2 catecholamine biosynthetic enzyme and GnRH neuropeptide precursor protein expression. Lack of effect of lactate on hypoglycemic patterns of GnRH AMPK activity suggests that this sensor is uninvolved in metabolic-inhibition of positive-feedback-stimulated hypophysiotropic signaling to pituitary gonadotropes.<br /> (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- AMP-Activated Protein Kinases metabolism
Animals
Blood Glucose drug effects
Drug Administration Routes
Drug Administration Schedule
Estradiol pharmacology
Female
Gene Expression Regulation drug effects
Hypoglycemia chemically induced
Hypoglycemia drug therapy
Insulin toxicity
Luteinizing Hormone metabolism
Neuropeptides metabolism
Ovariectomy
Proto-Oncogene Proteins c-fos metabolism
Rats
Rats, Sprague-Dawley
Adrenergic Neurons drug effects
Estradiol analogs & derivatives
Gonadotropin-Releasing Hormone metabolism
Hypoglycemia metabolism
Lactic Acid administration & dosage
Preoptic Area cytology
Rhombencephalon drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 298
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 25934033
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2015.04.049