+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Adaptation of arcuate insulin receptor, estrogen receptor-alpha, estrogen receptor-beta, and type-II glucocorticoid receptor gene profiles to chronic intermediate insulin-induced hypoglycemia in estrogen-treated ovariectomized female rats

Adaptation of arcuate insulin receptor, estrogen receptor-alpha, estrogen receptor-beta, and type-II glucocorticoid receptor gene profiles to chronic intermediate insulin-induced hypoglycemia in estrogen-treated ovariectomized female rats

Journal of Molecular Neuroscience 41(2): 304-309

Insulin and corticosterone signal energy surfeit and deficiency, respectively, to metabolic structures in the brain, including the hypothalamic arcuate nucleus (ARH). This peripheral input may be subject to ovarian control, since ovariectomy (OVX) increases insulin receptor transcripts and decreases glucocorticoid receptor protein in the hypothalamus. The present studies examined the hypothesis that estradiol regulates basal and hypoglycemic patterns of ARH insulin and glucocorticoid receptor mRNA expression, and governs habituation of these gene profiles to recurring intermediate insulin administration. The premise that estrogen receptor-alpha (ERalpha) and beta (ERbeta) gene profiles may be regulated differentially during acute and chronic hypoglycemia in the presence of estradiol was also evaluated. Insulin receptor-beta chain (InsRb), type-II glucocorticoid receptor (GR), ERalpha, and ERbeta mRNA levels in ARH tissue microdissected from estradiol benzoate (EB)- and oil-implanted OVX rats after single or serial sc neutral protamine Hagedorn insulin (NPH) injection were measured by quantitative real-time RT-PCR. ARH InsRb gene profiles were decreased, relative to baseline, after either one or four NPH injections in OVX + EB rats; mean mRNA levels were significantly lower after serial dosing since basal InsRb transcripts were diminished by precedent NPH treatment. InsRb transcription rates did not differ among OVX + oil treatment groups. Acute insulin elevated ARH GR mRNA relative to baseline in both EB- and oil-implanted rats. Prior NPH injections increased basal GR gene expression and suppressed transcriptional reactivity to a fourth dose of NPH in OVX + EB, but not OVX + oil animals. ARH ERalpha and ERbeta mRNA levels were increased or decreased, respectively, after one insulin dose in OVX + EB rats. Baseline expression of these genes was correspondingly augmented or suppressed after precedent NPH treatment, but ERalpha and ERbeta transcripts were not modified relative to these adjusted baselines after a fourth NPH dose. In the presence of estradiol, ARH InsRb and GR gene profiles exhibit divergent modifications during acute NPH-induced hypoglycemia, as well as opposite adjustments in baseline expression after serial NPH dosing. GR transcriptional acclimation to recurring NPH administration was also estrogen-dependent. Further research is needed to characterize potential effects of adjustments in ARH neuronal sensitivity to insulin and corticosterone on ARH metabolic neurotransmitter release during and after intermediate insulin-induced hypoglycemia in females. The current evidence for converse effects of NPH on ARH ERalpha and ERbeta gene profiles in the presence of estradiol supports the need to identify ARH-directed metabolic activities governed by each ER subtype, including metabolic hormone receptor expression, and to assess the impact of NPH-induced habituation of ER gene profiles on those functions.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 051367563

Download citation: RISBibTeXText

PMID: 19953342

DOI: 10.1007/s12031-009-9314-4

Related references

Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Research 62(15): 4419-4426, 2002

Estrogen receptor transcription and transactivation: Estrogen receptor alpha and estrogen receptor beta: regulation by selective estrogen receptor modulators and importance in breast cancer. Breast Cancer Research 2(5): 335-344, 2001

Tamoxifen regulation of bone growth and endocrine function in the ovariectomized rat: discrimination of responses involving estrogen receptor α/estrogen receptor β, G protein-coupled estrogen receptor, or estrogen-related receptor γ using fulvestrant (ICI 182780). Journal of Pharmacology and Experimental Therapeutics 338(1): 246-254, 2011

Effects of estradiol, benzophenone-2 and benzophenone-3 on the expression pattern of the estrogen receptors (ER) alpha and beta, the estrogen receptor-related receptor 1 (ERR1) and the aryl hydrocarbon receptor (AhR) in adult ovariectomized rats. Toxicology 205(1-2): 123-130, 2004

Natural killer cells express estrogen receptor-alpha and estrogen receptor-beta and can respond to estrogen via a non-estrogen receptor-alpha-mediated pathway. Cellular Immunology 214(1): 12-20, 2002

In the absence of estrogen receptor alpha, estrogen promotes bone resorption via estrogen receptor beta in female mice. Journal of Bone & Mineral Research 16(Suppl 1): S551, 2001

Dibutyl Phthalate (DBP)-Induced Apoptosis and Neurotoxicity are Mediated via the Aryl Hydrocarbon Receptor (AhR) but not by Estrogen Receptor Alpha (ERα), Estrogen Receptor Beta (ERβ), or Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Mouse Cortical Neurons. Neurotoxicity Research 31(1): 77-89, 2016

Progesterone receptor, estrogen receptor alpha, and the type II glucocorticoid receptor are coexpressed in the same neurons of the ovine preoptic area and arcuate nucleus: a triple immunolabeling study. Biology of Reproduction 67(5): 1605-1612, 2002

Hepatic stellate cells contain the functional estrogen receptor beta but not the estrogen receptor alpha in male and female rats. Biochemical and Biophysical Research Communications 286(5): 1059-1065, 2001

Both estrogen receptor alpha and estrogen receptor beta agonists enhance cell proliferation in the dentate gyrus of adult female rats. Neuroscience 141(4): 1793-1800, 2006

A novel gene STYK1/NOK is upregulated in estrogen receptor-alpha negative estrogen receptor-beta positive breast cancer cells following estrogen treatment. Molecular Biology Reports 35(1): 23-27, 2007

Estrogen receptor alpha but not estrogen receptor beta knockout mice lack astrocyte responsiveness to estradiol in the arcuate. Society for Neuroscience Abstracts 27(1): 1082, 2001

Quantitative analysis of estrogen-related receptor alpha, estrogen receptor alpha and estrogen receptor beta mRNAs throughout bovine mammary gland development. Journal of Dairy Science 86(Suppl. 1): 118, 2003

Requirement of estrogen receptor-alpha in insulin-like growth factor-1 (IGF-1)-induced uterine responses and in vivo evidence for IGF-1/estrogen receptor cross-talk. Journal of Biological Chemistry 277(10): 8531-8537, 2001

Estrogen receptor beta, but not alpha, mediates estrogen's effect on cocaine-induced reinstatement of extinguished cocaine-seeking behavior in ovariectomized female rats. Neuropsychopharmacology 32(6): 1334-1345, 2007