Effects of Estradiol on Glucoprivic Transactivation of Catecholaminergic Neurons in the Female Rat Caudal Brainstem

Abstract

Hyperphagic and hypothalamic neuroendocrine responses to acute glucose deprivation are modified by the ovarian steroid estradiol (E). Observations of genomic activation of catecholaminergic (CA) neurons in the hindbrain lateral reticular nucleus, nucleus of the solitary tract, and area postrema (AP) by glucopenia support their potential function in pathways mediating regulatory effects of this metabolic challenge within the brain. Expression of E receptors by these cells suggests that their activity may be sensitive to steroid modulation during glucopenia. The present studies investigated the role of E on transcriptional activation of caudal brainstem CA neurons by the glucose antimetabolite, 2-deoxy-D-glucose (2DG). Ovariectomized rats were implanted with s.c. Silastic capsules containing E (30 or 250 µg/ml) or sesame oil, and injected i.p. 7 days later with 400 mg 2DG/kg or saline. Tyrosine hydroxylase (TH)-immunoreactive (-ir) neurons in the C₁/A₁, C₂, C₃, A₂, A₅, and A₆ cell groups and AP were colabeled for Fos following antimetabolite administration, whereas vehicle injection resulted in negligible nuclear staining of these cells. With the exception of A₂, A₆, and AP cells, mean numbers of Fos- and TH-/Fos-ir-positive neurons in these brain sites did not differ between E- and sesame oil-implanted groups. Numbers of TH-positive A₂ and A₆ neurons that expressed Fos in response to 2DG were significantly greater in rats implanted with the high E dose vs. either the low steroid dose or sesame oil. These results show that the magnitude of cellular Fos labeling within discrete hindbrain CA neuron populations varies in accordance with circulating E levels. These findings suggest that E may exert potential modulatory effects on glucoprivic activation of the Fos stimulus/transcription cascade and consequent compensatory genomic responses within specific areas of the female rat caudal brainstem.

Effects of Estradiol on Acute and Recurrent Insulin-Induced Hypoglycemia-Associated Patterns of Arcuate Neuropeptide Y, Proopiomelanocortin, and Cocaine- and Amphetamine-Related Transcript Gene Expression in the Ovariectomized Rat

“…Ten days before the experiments, adult female Sprague Dawley rats (weighing 220–290 g) underwent bilateral OVX, and were implanted with a Silastic capsule containing estradiol benzoate (EB; 30 µg/ml, 10 mm/100 g) or the vehicle safflower oil. Studies performed in our laboratory have shown that this treatment results in circulating estradiol concentrations that approximate the hormone levels detected on metestrus in intact cycling female rats [23]. Beginning on day 1, the animals in each group were injected with an intermediate-release formulation of insulin or diluent according to the following schedule: (1) subcutaneous injection of diluent on days 1–4 (n = 6); (2) subcutaneous injection of diluent on days 1–3, followed by 12.5 U/kg Humulin NPH (NPH) on day 4 (n = 6); (3) subcutaneous injection of NPH on days 1–3, followed by diluent on day 4, or (4) subcutaneous injection of NPH on days 1–4 (n = 6).…”

Effects of Estradiol on Glycemic and CNS Neuronal Activational Responses to Recurrent Insulin-Induced Hypoglycemia in the Ovariectomized Female Rat

“…filled with 30 µg estradiol benzoate (E)/ml (Sigma Aldrich, St. Louis, Mo., USA) [11] dissolved in safflower seed oil (O) alone. We previously reported that this dose results in circulating estradiol levels that approximate values measured on metestrus in intact cycling animals [11]. Each animal was implanted with an indwelling intracardiac venous catheter on the 7th day of the study.…”

Glucose sensing and the pathogenesis of obesity and type 2 diabetes

“…25,26 GE and GI neurons are also present in the brainstem, in particular in the area postrema, the nucleus of solitary tract (NTS), the dorsal motor nucleus of the vagus and the basolateral medulla in regions containing A1 and C1 neurons. [27][28][29][30][31][32] The NTS is a structure that integrates internal signals and transmits them to the hypothalamus. Neurons in the NTS and the basolateral medulla are sensitive to small variations in glycemia and may regulate the activity of hypothalamic neurons, in particular those from the lateral hypothalamus and the VMH, with which they are synaptically connected.…”