A source on BRCA1 Selenium and DCA

Insulin-like growth factor 1 (IGF-1): a growth hormone

Prof Z. Laron

http://mp.bmjjournals.com/cgi/content/full/54/5/311

Abstract
Aim—To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process.
Methods—To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice.
Results—Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100–136 cm for female and 109–138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8–9 cm in the first year of treatment, compared with 10–12 cm/year during GH treatment of IGHD. The growth rate in following years was 5–6.5 cm/year.
Conclusion—IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH.
Key Words: insulin-like growth factor I • growth hormones • Laron syndrome • growth
Z Laron
Endocrinology and Diabetes Research Unit, WHO Collaborating Center for the Study of Diabetes in Youth, Schneider Children's Medical Center, Tel Aviv University, 14 Kaplan Street, Petah Tikva 49202, Tel Aviv, Israel
Correspondence: Professor Laron laronz@clalit.org.il
Accepted for publication April 24, 2001
Clin Pathol: Mol Pathol 2001; 54:311-316
© 2001 Journal of Clinical Pathology
http://mp.bmjjournals.com/cgi/content/full/54/5/311

http://mp.bmjjournals.com/cgi/external_ref?access_num=11577173&link_type=PUBMED

[[.....IGF-1 and IGF-2 were identified in 1957 by Salmon and Daughaday8 and designated "sulphation factor" by their ability to stimulate 35-sulphate incorporation into rat cartilage. Froesch et al described the non-suppressible insulin-like activity (NSILA) of two soluble serum components (NSILA I and II).9 In 1972, the labels sulphation factor and NSILA were replaced by the term "somatomedin", denoting a substance under control and mediating the effects of GH.10 In 1976, Rinderknecht and Humbel11 isolated two active substances from human serum, which owing to their structural resemblance to proinsulin were renamed "insulin-like growth factor 1 and 2" (IGF-1 and 2). IGF-1 is the mediator of the anabolic and mitogenic activity of GH....]]

[[.....The IGFs are members of a family of insulin related peptides that include relaxin and several peptides isolated from lower invertebrates.13 IGF-1 is a small peptide consisting of 70 amino acids with a molecular weight of 7649 Da....]]

http://www.diva-portal.org/diva/getDocument?urn_nbn_se_su_diva-121-1__fulltext.pdf

Abstract
Diabetic neuropathy is believed to arise due to oxidative stress following
hyperglycemic situations. Uncoupling proteins (UCPs) constitute a subgroup
of mitochondrial transporter proteins with putative antioxidant properties. By
dissipating the proton gradient over the mitochondrial inner membrane, these
proteins reduce the mitochondrial inner membrane potential (MMP), and
thereby, the mitochondrial production of reactive oxygen species (ROS) is
decreased. In this thesis I have examined the regulation of UCP2, UCP3, and
UCP4 by the neuroprotective hormone insulin-like growth factor type 1 (IGF-
1). I have also investigated the possible involvement of UCP3 in IGF-1-
mediated neuroprotection following high glucose treatments. All studies were
performed using human neuroblastoma SH-SY5Y cells as an in vitro cell
model. The major findings were as follows:
i. Native SH-SY5Y cells expressed UCP2, UCP3, and UCP4.
ii. UCP3 was upregulated by IGF-1 via activation of the IGF-1 receptor. IGF-
1 increased UCP3 mRNA and protein levels primarily via activation of the
“classical” anti-apoptotic phosphatidyl inositol 3 (PI3)-kinase signaling
pathway, as shown by incubation with specific inhibitors of the PI3-kinase
and mitogen activated protein (MAP) kinase signaling pathways.
iii. UCP2 and UCP4 protein levels were only marginally or not at all
regulated by IGF-1. These UCPs are probably not involved in IGF-1-
mediated neuroprotection.
iv. High glucose concentrations reduced the UCP3 protein levels in highly
differentiated SH-SY5Y cells. Concomitantly, the MMP and the levels of
ROS and glutathione increased, whereas the number of neurites per cell
was reduced. This supports an antioxidant and neuroprotective role of
UCP3
v. IGF-1 prevented the glucose-induced reduction in UCP3 protein levels. In
parallel, the effects on MMP, levels of ROS and glutathione, and number
of neurites per cell were abolished or significantly reduced. These data
suggest that UCP3 is involved in IGF-1-mediated neuroprotection.

SPONTANEOUS DIURNAL TSH SECRETION IS ENHANCED IN PROPORTION TO CIRCULATING LEPTIN IN OBESE PREMENOPAUSAL WOMEN

http://jcem.endojournals.org/cgi/content/short/jc.2005-0003v1

Context. Recent evidence implicates leptin as an important modulator of thyroid axis activity.

Objective. To study spontaneous 24 h TSH secretion and 24 h circulating leptin concentrations in obese and lean women.

Design. Prospective parallel study (2004).

Setting. Clinical Research Center LUMC.

Participants. 12 healthy obese premenopausal women (BMI 33.2 ± 0.9 kg/m2) and 11 lean controls (BMI 21.4 ± 0.5 kg/m2) were studied in the follicular phase of their menstrual cycle.

Intervention(s). None.

Main Outcome Measure(s). Spontaneous 24 h TSH concentrations (10 min time intervals) and secretion, calculated using waveform-independent deconvolution technique (Pulse). 24 h circulating leptin concentrations (20 min time intervals).

Results. Mean TSH concentration (obese 1.9 ± 0.2 vs. lean 1.1 ± 0.1 mU/L, P = 0.009) and secretion rate (obese 43.4 ± 5.5 vs. in lean 26.1 ± 2.2 mU/liter distribution volume. 24 h, P = 0.011) were substantially enhanced in obesity, whereas the fasting free thyroxine concentrations were similar (free T4 in obese 15.4 ± 1.5 vs. in lean 16.4 ± 1.5 pmol/L, P = 0.147). TSH secretion was positively related to 24 h leptin concentrations (R2 = 0.31, P = 0.007).

Conclusions. TSH release is enhanced in the face of normal plasma free thyroxine concentrations in obese premenopausal women and hyperleptinemia may well be involved in this neuroendocrine alteration.

Key words: Hormone Rhythms • Body Fat Distribution • Obesity • Circadian

http://edrv.endojournals.org/cgi/content/abstract/26/7/944

Selenium, the Thyroid, and the Endocrine System

Recent identification of new selenocysteine-containing proteins has revealed relationships between the two trace elements selenium (Se) and iodine and the hormone network. Several selenoproteins participate in the protection of thyrocytes from damage by H(2)O(2) produced for thyroid hormone biosynthesis. Iodothyronine deiodinases are selenoproteins contributing to systemic or local thyroid hormone homeostasis. The Se content in endocrine tissues (thyroid, adrenals, pituitary, testes, ovary) is higher than in many other organs. Nutritional Se depletion results in retention, whereas Se repletion is followed by a rapid accumulation of Se in endocrine tissues, reproductive organs, and the brain. Selenoproteins such as thioredoxin reductases constitute the link between the Se metabolism and the regulation of transcription by redox sensitive ligand-modulated nuclear hormone receptors. Hormones and growth factors regulate the expression of selenoproteins and, conversely, Se supply modulates hormone actions. Selenoproteins are involved in bone metabolism as well as functions of the endocrine pancreas and adrenal glands. Furthermore, spermatogenesis depends on adequate Se supply, whereas Se excess may impair ovarian function. Comparative analysis of the genomes of several life forms reveals that higher mammals contain a limited number of identical genes encoding newly detected selenocysteine-containing proteins.

PMID: 16174820 [PubMed - in process]

Serum 3,3',5'-Triiodothyronine (rT3) and 3,5,3'-Triiodothyronine/rT3 Are Prognostic Markers in Critically Ill Patients and Are Associated with Postmortem Tissue Deiodinase Activities

http://jcem.endojournals.org/cgi/content/abstract/90/8/4559

Robin P. Peeters, Pieter J. Wouters, Hans van Toor, Ellen Kaptein, Theo J. Visser and Greet Van den Berghe

Introduction and Methods: Critical illness is associated with reduced TSH and thyroid hormone secretion, and with changes in peripheral thyroid hormone metabolism, resulting in low serum T3 and high rT3. In 451 critically ill patients who received intensive care for more than 5 d, serum thyroid parameters were determined on d 1, 5, 15, and last day (LD). All patients had been randomized for intensive or conventional insulin treatment. Seventy-one patients died, and postmortem liver and skeletal muscle biopsies were obtained from 50 of them for analysis of deiodinase (D1–3) activities.

Results: Insulin treatment did not affect thyroid parameters. On d 1, rT3 was higher and T3/rT3 was lower in nonsurvivors as compared with survivors (P = 0.001). Odds ratio for survival of the highest vs. the lowest quartile was 0.3 for rT3 and 2.9 for T3/rT3. TSH, T4, and T3 were lower in nonsurvivors from d 5 until LD (P less than 0.001). TSH, T4, T3, and T3/rT3 increased over time in survivors, but decreased or remained unaltered in nonsurvivors. Liver D1 activity was positively correlated with LD serum T3/rT3 (R = 0.83, P less than 0.001) and negatively correlated with rT3 (R = –0.69, P less than 0.001). Both liver and skeletal muscle D3 activity were positively correlated with LD serum rT3 (R = 0.32, P = 0.02 and R = 0.31, P = 0.03).

Conclusion: In critically ill patients who required more than 5 d of intensive care, rT3 and T3/rT3 were already prognostic for survival on d 1. On d 5, T4, T3, but also TSH levels are higher in patients who will survive. Serum rT3 and T3/rT3 were correlated with postmortem tissue deiodinase activities.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=16174820&dopt=Abstract

Recent identification of new selenocysteine-containing proteins has revealed relationships between the two trace elements selenium (Se) and iodine and the hormone network. Several selenoproteins participate in the protection of thyrocytes from damage by H(2)O(2) produced for thyroid hormone biosynthesis. Iodothyronine deiodinases are selenoproteins contributing to systemic or local thyroid hormone homeostasis. The Se content in endocrine tissues (thyroid, adrenals, pituitary, testes, ovary) is higher than in many other organs. Nutritional Se depletion results in retention, whereas Se repletion is followed by a rapid accumulation of Se in endocrine tissues, reproductive organs, and the brain. Selenoproteins such as thioredoxin reductases constitute the link between the Se metabolism and the regulation of transcription by redox sensitive ligand-modulated nuclear hormone receptors. Hormones and growth factors regulate the expression of selenoproteins and, conversely, Se supply modulates hormone actions. Selenoproteins are involved in bone metabolism as well as functions of the endocrine pancreas and adrenal glands. Furthermore, spermatogenesis depends on adequate Se supply, whereas Se excess may impair ovarian function. Comparative analysis of the genomes of several life forms reveals that higher mammals contain a limited number of identical genes encoding newly detected selenocysteine-containing proteins.

PMID: 16174820 [PubMed - in process]

Edit:-
Serum Selenium tested 78mcg/L (range 70 - 130)