Sex-dimorphic neuroestradiol regulation of ventromedial hypothalamic nucleus glucoregulatory transmitter and glycogen metabolism enzyme protein expression in the rat.
Animals
Aromatase Inhibitors
/ pharmacology
Estradiol
/ physiology
Estrogen Replacement Therapy
Female
Gene Expression Regulation
/ genetics
Glucose
/ metabolism
Glutamate Decarboxylase
/ metabolism
Glutaminase
/ metabolism
Glycogen
/ metabolism
Glycogen Synthase
/ metabolism
Letrozole
/ pharmacology
Malate Dehydrogenase
/ metabolism
Male
Nitric Oxide Synthase
/ metabolism
Ovariectomy
Rats
Rats, Sprague-Dawley
Sex Characteristics
Ventromedial Hypothalamic Nucleus
/ metabolism
Aromatase
Glutamate decarboxylase65/67
Insulin-induced hypoglycemia
Letrozole
Neuronal nitric oxide synthase
Ventromedial hypothalamic nucleus
Journal
BMC neuroscience
ISSN: 1471-2202
Titre abrégé: BMC Neurosci
Pays: England
ID NLM: 100966986
Informations de publication
Date de publication:
25 11 2020
25 11 2020
Historique:
received:
18
06
2020
accepted:
30
10
2020
entrez:
26
11
2020
pubmed:
27
11
2020
medline:
3
9
2021
Statut:
epublish
Résumé
Ventromedial hypothalamic nucleus (VMN) gluco-regulatory transmission is subject to sex-specific control by estradiol. The VMN is characterized by high levels of aromatase expression. The aromatase inhibitor letrozole (LZ) was used with high-resolution microdissection/Western blot techniques to address the hypothesis that neuroestradiol exerts sex-dimorphic control of VMN neuronal nitric oxide synthase (nNOS) and glutamate decarboxylase VMN aromatase protein content was similar between sexes. Intracerebroventricular LZ infusion of testes-intact male and ovariectomized, estradiol-replaced female rats blocked insulin-induced hypoglycemic (IIH) up-regulation of this profile. LZ exerted sex-contingent effects on basal VMN nNOS and GAD expression, but blocked IIH-induced NO stimulation and GAD suppression in each sex. Sex-contingent LZ effects on basal and hypoglycemic patterns of GPbb and GPmm expression occurred at distinctive levels of the VMN. LZ correspondingly down- or up-regulated baseline pyruvate recycling pathway marker protein expression in males (glutaminase) and females (malic enzyme-1), and altered INS effects on those proteins. Results infer that neuroestradiol is required in each sex for optimal VMN metabolic transmitter signaling of hypoglycemic energy deficiency. Sex differences in VMN GP variant protein levels and sensitivity to aromatase may correlate with sex-dimorphic glycogen mobilization during this metabolic stress. Neuroestradiol may also exert sex-specific effects on glucogenic amino acid energy yield by actions on distinctive enzyme targets in each sex.
Sections du résumé
BACKGROUND
Ventromedial hypothalamic nucleus (VMN) gluco-regulatory transmission is subject to sex-specific control by estradiol. The VMN is characterized by high levels of aromatase expression.
METHODS
The aromatase inhibitor letrozole (LZ) was used with high-resolution microdissection/Western blot techniques to address the hypothesis that neuroestradiol exerts sex-dimorphic control of VMN neuronal nitric oxide synthase (nNOS) and glutamate decarboxylase
RESULTS
VMN aromatase protein content was similar between sexes. Intracerebroventricular LZ infusion of testes-intact male and ovariectomized, estradiol-replaced female rats blocked insulin-induced hypoglycemic (IIH) up-regulation of this profile. LZ exerted sex-contingent effects on basal VMN nNOS and GAD expression, but blocked IIH-induced NO stimulation and GAD suppression in each sex. Sex-contingent LZ effects on basal and hypoglycemic patterns of GPbb and GPmm expression occurred at distinctive levels of the VMN. LZ correspondingly down- or up-regulated baseline pyruvate recycling pathway marker protein expression in males (glutaminase) and females (malic enzyme-1), and altered INS effects on those proteins.
CONCLUSIONS
Results infer that neuroestradiol is required in each sex for optimal VMN metabolic transmitter signaling of hypoglycemic energy deficiency. Sex differences in VMN GP variant protein levels and sensitivity to aromatase may correlate with sex-dimorphic glycogen mobilization during this metabolic stress. Neuroestradiol may also exert sex-specific effects on glucogenic amino acid energy yield by actions on distinctive enzyme targets in each sex.
Identifiants
pubmed: 33238883
doi: 10.1186/s12868-020-00598-w
pii: 10.1186/s12868-020-00598-w
pmc: PMC7687823
doi:
Substances chimiques
Aromatase Inhibitors
0
Estradiol
4TI98Z838E
Letrozole
7LKK855W8I
Glycogen
9005-79-2
Malate Dehydrogenase
EC 1.1.1.37
malate dehydrogenase (decarboxylating)
EC 1.1.1.39
Nitric Oxide Synthase
EC 1.14.13.39
Glycogen Synthase
EC 2.4.1.11
Glutaminase
EC 3.5.1.2
Glutamate Decarboxylase
EC 4.1.1.15
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
51Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK109382
Pays : United States
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