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Hindbrain 5'-Adenosine Monophosphate-activated Protein Kinase Mediates Short-term Food Deprivation Inhibition of the Gonadotropin-releasing Hormone-Luteinizing Hormone Axis: Role of Nitric Oxide.

Abstract：

:Hindbrain-derived stimuli restrain the gonadotropin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) reproductive neuroendocrine axis during energy insufficiency. Interruption of food intake, planned or unplanned, is emblematic of modern life. This study investigated the premise that the hindbrain energy sensor 5'-adenosine monophosphate-activated protein kinase (AMPK) inhibits reproductive neuroendocrine function in short term, e.g. 18-h food-deprived (FD) estradiol (E)-implanted ovariectomized female rats. Intra-caudal fourth ventricular administration of the AMPK inhibitor Compound C (Cc) reversed FD-induced inhibition of rostral preoptic (rPO) GnRH protein expression and LH release in animals given E to replicate proestrus (high-E dose-, but not metestrus (low-E dose)-stage plasma steroid levels. FD caused Cc-reversible augmentation or diminution of preoptic norepinephrine (NE) activity in high- versus low-E rats, respectively, and AMPK-independent reductions in hypothalamic NE accumulation in the latter. Nitric oxide (NO) and kisspeptin are key stimulatory signals for the preovulatory LH surge. Here, FD inhibited rPO neuronal nitric oxide synthase protein expression in high-, but not low-E-dosed animals. Lateral ventricular delivery of the NO donor 3-morpholinosydnonimine (SIN-1) reversed inhibitory GnRH and LH responses to FD in high-E rats, and normalized rPO Vglut2, anteroventral periventricular KiSS1, and dorsomedial hypothalamic RFRP-3 mRNA and/or protein profiles. Data show that FD curtails reproductive neuroendocrine outflow by hindbrain AMPK-dependent mechanisms in the presence of peak estrous cycle E levels. Results indicate that neural networks linking this sensor to GnRH neurons likely involve NO signaling, which may function upstream of one or more neurotransmitters identified here by SIN-1-reversible inhibitory responses to FD.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Shakya M,Shrestha PK,Briski KP

doi

10.1016/j.neuroscience.2018.04.040

subject

Has Abstract

pub_date

2018-07-15 00:00:00

pages

46-59

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(18)30307-5

journal_volume

383

pub_type

杂志文章

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Hindbrain 5'-Adenosine Monophosphate-activated Protein Kinase Mediates Short-term Food Deprivation Inhibition of the Gonadotropin-releasing Hormone-Luteinizing Hormone Axis: Role of Nitric Oxide.