Sex-dimorphic aromatase regulation of ventromedial hypothalamic nucleus glycogen content in euglycemic and insulin-induced hypoglycemic rats

NEUROSCIENCE LETTERS

卷:737

Article

Ibrahim, Mostafa M. H.¹  Uddin, Md. Main¹  Bheemanapally, Khaggeswar¹  Briski, Karen P.¹ 

[1] Univ Louisiana Monroe, Sch Basic Pharmaceut & Toxicol Sci, Coll Pharm, 356 Bienville Bldg,1800 Bienville Dr, Monroe, LA 71201 USA

关键词: Letrozole;    Aromatase;    Insulin-induced hypoglycemia;    Ventromedial hypothalamic nucleus;    Glycogen;    Sex differences;   

DOI  :  10.1016/j.neulet.2020.135284

来源: Elsevier

【 摘 要 】

Estrogen receptors control hypothalamic astrocyte glycogen accumulation in vitro. Glycogen metabolism impacts metabolic transmitter signaling in the ventromedial hypothalamic nucleus (VMN), a key glucoregulatory structure. Aromatase, the enzyme that converts testosterone to estradiol, is expressed at high levels in the VMN. Here, the aromatase inhibitor letrozole (Lz) was used alongside high-resolution microdissection/UPHLC-electrospray ionization-mass spectrometric methods to determine if neuroestradiol imposes sex-specific control of VMN glycogen content during glucostasis and/or glucoprivation. Testes-intact male and estradiol-replaced ovariectomized female rats were pretreated by lateral ventricular letrozole (Lz) infusion prior to subcutaneous insulin (INS) injection. Vehicle-treated female controls exhibited higher VMN glycogen content compared to males. Lz increased VMN glycogen levels in males, not females. INS-induced hypoglycemia (IIH) elevated (males) or diminished (females) rostral VMN glycogen accumulation. Induction of IIH in Lz-pretreated animals reduced male VMN glycogen mass, but augmented content in females. Data provide novel evidence for regional variation, in both sexes, in glycogen reactivity to IIH. Results highlight sex-dimorphic neuroestradiol regulation of VMN glycogen amassment during glucostasis, e.g. inhibitory in males versus insignificant in females. Locally-generated estradiol is evidently involved in hypoglycemic enhancement of male VMN glycogen, but conversely limits glycogen content in hypoglycemic females. Further research is needed to characterize mechanisms that underlie the directional shift in aromatase regulation of VMN glycogen in eu-versus hypoglycemic male rats and gain in negative impact in hypoglycemic females.

【 授权许可】

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