THE hypothalamic neurotransmitter dopamine (DA) regulates pituitary se
cretion of the glucoregulatory hormones, growth hormone (GH) and adren
ocorticotropin (ACTH). The glucose antimetabolite, 2-deoxy-D-glucose (
2DG), elicits expression of the protooncogene product Fos, which is ex
pressed in hypothalamic structures where DA is synthesized. These stud
ies utilized dual-label immunocytochemistry to determine whether discr
ete DA neuron populations in this region of the brain exhibit Fos immu
noreactivity (-ir) in response to glucopenia. Ovariectomized female ra
ts implanted s.c. with exogenous estradiol or vehicle were injected wi
th 2DG (400 mg/kg, i.p.) or saline, and sacrificed 2 h later. Whereas
Fos-ir was negligible after saline administration, 2DG induced express
ion of Fos-ir by TH-ir neurons in the paraventricular (PVN), periventr
icular (Pe) and arcuate nuclei (ARC), and in the anterior hypothalamic
area (AHA). TH-ir neurons in the zona incerta did not express Fos-ir
following 2DG. Although mean numbers of co-labeled neurons in the Pe,
PVN and AHA did not differ between estradiol-and non-steroid-treated r
ats, the former group exhibited significantly higher numbers of TH-pos
itive plus Fos-positive neurons in the ARC in response to 2DG. These r
esults reveal the functional responsiveness of discrete DA neuron popu
lations to glucoprivation, and indicate that estradiol enhances cellul
ar accumulation of Fos-ir by ARC DA neurons during this metabolic chal
lenge.