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J Neurosci. 1999 Apr 15;19(8):3213-22.
Hormonal regulation of glutamate receptor gene expression in the anteroventral periventricular nucleus of the hypothalamus.

Gu G, Varoqueaux F, Simerly RB.

Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton, Oregon 97006, USA.

Glutamate plays an important role in mediating the positive feedback effects of ovarian steroids on gonadotropin secretion, and the preoptic region of the hypothalamus is a likely site of action of glutamate. The anteroventral periventricular nucleus (AVPV) of the preoptic region is an essential part of neural pathways mediating hormonal feedback on gonadotropin secretion, and it appears to provide direct inputs to gonadotropin releasing hormone (GnRH)-containing neurons. Immunohistochemistry and in situ hybridization were used in this study to define the distribution and hormonal regulation of glutamate receptor subtypes in the AVPV of juvenile female rats. Neurons that express the NMDAR1 receptor subtype are abundant in the AVPV, as are cells that express AMPA receptor subtypes (GluR1, GluR2, and GluR3 but not GluR4), and the AVPV appears to contain a dense plexus of NMDAR1-immunoreactive presynaptic terminals. However, AVPV neurons do not seem to express detectable levels of kainate receptor (GluR5, GluR6, and GluR7) or metabotropic receptor (mGluR1-6) subtypes. Treatment of ovariectomized juvenile rats with estradiol induced expression of GluR1 mRNA but did not alter levels of GluR2 or GluR3 mRNA. Treatment of estrogen-primed ovariectomized juvenile rats with progesterone caused an initial increase in GluR1 mRNA expression, followed by a small decrease 24 hr after treatment. In contrast, estrogen appears to suppress levels of NMDAR1 mRNA in the AVPV, which remained unchanged after progesterone treatment. Thus, one mechanism whereby ovarian steroids may provide positive feedback to GnRH neurons is by altering the sensitivity of AVPV neurons to glutamatergic activation.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10191334&dopt=Abstract

Intensive Care Med. 2002 Sep;28(9):1301-8. Epub 2002 Aug 09.
Endocrine measurements in survivors and non-survivors from critical illness.

Ray DC, Macduff A, Drummond GB, Wilkinson E, Adams B, Beckett GJ.

Department of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary, Lauriston Place, Edinburgh, EH3 9YW, UK. david.rad.ac.uk

OBJECTIVE: To compare measurements of thyroid and adrenal function between survivors and non-survivors in critical illness. DESIGN AND SETTING: Prospective, observational study at the medical/surgical intensive care unit (ICU) at Royal Infirmary of Edinburgh, Scotland. PATIENTS: 163 patients admitted to the intensive care unit over a 4-month period. INTERVENTIONS: We took blood samples within 1 h of ICU admission, and at 08:00 hours on the subsequent 2 days of ICU admission. We measured serum total (TT(4)) and free (fT(4)) thyroxine, total (TT(3)) and free (fT(3)) tri-iodothyronine, thyrotropin (TSH) and plasma cortisol concentrations. MEASUREMENTS AND RESULTS: TT(3) and TT(4) concentrations were significantly less in non-survivors than in survivors on admission and on day 1 but not on day 2. Cortisol concentrations were higher in non-survivors on admission and on day 1 but not on day 2. TSH, fT(3) and fT(4) concentrations did not differ significantly between survivors and non-survivors at any time. Only TT(4) and cortisol were independent predictors of outcome. Prediction of outcome from the admission sample values was not better than using APACHE II scoring. CONCLUSIONS: Thyroid hormone and cortisol concentrations differ between survivors and non-survivors on admission to intensive care, but the values overlap. These differences do not allow accurate prediction of outcome from critical illness.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12209281&dopt=Abstract

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In murine Taenia crassiceps cysticercosis, females sustain larger intensities of infection than males. However, during chronic infection, this difference disappears and males show a feminization process. To further study the role of two cytokines, interleukin-6 (IL-6) and macrophage-migration inhibitory factor (MIF), known to be involved in immunoendocrinological processes during sex-associated susceptibility in cysticercosis, IL-6 and MIF gene knockout (KO) mice were infected, and the number of parasites and serum sex-steroid levels were measured. Results show that IL-6 and MIF KO mice of both genders infected with T. crassiceps cysticerci harbor similar numbers of parasites, with no change in sex-hormone levels. However, in wild-type strains, females have twice as many parasites as males. At the same time, there is a decrease of 80% in testosterone and dihydrotestosterone serum levels, and a 100-fold increase in the levels of estradiol in infected male mice. These results suggest a role for both IL-6 and MIF genes in sex-associated susceptibility in murine T. crassiceps cysticercosis.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12209330&dopt=Abstract

Eur J Clin Nutr. 2002 Sep;56(9):925-7.
Plasma deoxycholic acid concentration is elevated in postmenopausal women with newly diagnosed breast cancer.

Costarelli V, Sanders TA.

Nutrition Food and Health Research Centre, King's College London, London, UK. costarbu.ac.uk

OBJECTIVE: High concentrations of plasma deoxycholic acid (DCA) are found in human breast cyst fluid and it has been hypothesised that this may be related to risk of breast cancer. The aim of this pilot study was to ascertain whether plasma bile acid concentrations were greater in women with breast cancer. DESIGN: A case-control study comparing postmenopausal women with breast cancer with healthy controls was conducted. SUBJECTS: Twenty Caucasian postmenopausal breast cancer patients were recruited at the time of diagnosis together with 20 healthy controls matched for age and body mass index. Exclusion criteria included any treatment for breast cancer, use of hormone replacement therapy in the last 12 months, diabetes mellitus, a history of liver or gall bladder disease or abnormal liver function. MEASUREMENTS: Fasting plasma bile acid concentrations were determined by gas-liquid chromatography/mass spectrometry. RESULTS: The mean plasma DCA concentration was 52% higher (P=0.012) in patients with breast cancer compared with controls. CONCLUSION: These results support the hypothesis that DCA may be involved in the aetiology of breast cancer.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12209383&dopt=Abstract

Int J Cancer. 2002 Sep 1;101(1):17-22.
Non-competitive steroid inhibition of oestrogen receptor functions.

Puddefoot JR, Barker S, Glover HR, Malouitre SD, Vinson GP.

School of Biological Sciences, Queen Mary, University of London, United Kingdom.

Currently available antioestrogens, such as tamoxifen, are competitive inhibitors that bind to the ligand binding sites of oestrogen receptors, ERalpha and ERbeta. The search for alternative anti-hormone therapies is prompted by the need for drugs that are effective when tumours become tamoxifen resistant. The existence of different receptor isoforms also raise the possibility of improving selectivity. Earlier use of the 3beta-hydroxysteroid dehydrogenase inhibitor, trilostane (4alpha,5- epoxy-17beta-hydroxy-3-oxo-5alpha-androstane-2alpha-carbonitrile), suggested that it had beneficial actions in breast cancer that were only partially attributable to inhibition of steroidogenesis. The present studies on the interactions of trilostane with oestrogen receptors show that it (i) inhibits oestrogen-stimulated proliferation in MCF-7 breast cancer cells, (ii) enhances the affinity of oestradiol binding to ER in rat uteri and specifically increases oestradiol binding to an ERbeta-like isoform, (iii) inhibits ERalpha and ERbeta binding to the classical vitellogenin gene oestrogen response element (ERE) and (iv) inhibits oestrogen-stimulated gene transcription in ERE-linked reporter systems in MCF-7 cells. The results demonstrate a novel, presumably allosteric, mode of antioestrogen action. The beneficial actions of trilostane in breast cancer may be attributed to the combination of this antioestrogen effect with its well documented suppression of steroidogenesis. 2002 Wiley-Liss, Inc.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12209583&dopt=Abstract

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