The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.

/pdf/overweight-obesity-and-cancer-epidemiological-evidence-and-3aap682afc.pdf

Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms

Insulin-like growth factor-I (IGF-I) is a mitogen for prostate epithelial cells. To investigate associations between plasma IGF levels and prostate cancer risk, a nested case-control study within the Physicians' Health Study was conducted on prospectively collected plasma from 152 cases and 152 controls. A strong positive association was observed between IGF-I levels and prostate cancer risk. Men in the highest quartile of IGF-I levels had a relative risk of 4.3 (95 percent confidence interval 1.8 to 10.6) compared with men in the lowest quartile. This association was independent of baseline prostate-specific antigen levels. Identification of plasma IGF-I as a predictor of prostate cancer risk may have implications for risk reduction and treatment.

https://science.sciencemag.org/content/sci/279/5350/563.full.pdf

Plasma Insulin-Like Growth Factor-I and Prostate Cancer Risk: A Prospective Study

There is currently widespread interest in the IGFs (IGF-I and IGF-II) and their roles in the regulation of growth and differentiation of an ever increasing number of tissues are being reported. This selective review focused on the current state of our knowledge about the structure of mammalian IGFs and the multiple forms of mRNAs which arise from alternative splicing and promoter sites which arise from gene transcription. Current progress in the immunological measurement of the IGF is reviewed including different strategies for avoiding binding protein interference. The results of measurements of serum IGF-I and IGF-II in fetus and mother and at various stages of postnatal life are described. Existing knowledge of the concentration of these peptides in body fluids and tissues are considered. Last, an attempt is made to indicate circumstances in which the IGFs are exerting their actions in an autocrine/paracrine mode and when endocrine actions predominate. In the latter context it was concluded that an important role for GH action on skeletal tissues via hepatic production of IGF-I and endocrine action of IGF-I on growth cartilage is likely.

Insulin-Like Growth Factors I and II. Peptide, Messenger Ribonucleic Acid and Gene Structures, Serum, and Tissue Concentrations

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673697103841.pdf

Circulating concentrations of insulin-like growth factor I and risk of breast cancer

Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause vs. treatment; physical activity and inactivity mechanisms differ; gene-environment interaction [including aerobic training adaptations, personalized medicine, and co-twin physical activity]; and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [Accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, preeclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life.

/pdf/lack-of-exercise-is-a-major-cause-of-chronic-diseases-3lw4tu4drr.pdf

Lack of exercise is a major cause of chronic diseases

Studies of prolactin secretion in human pregnancy.

Intracerebroventricular administration of ILA's, a preparation enriched in insulin-like growth factors, caused a marked decrease in growth hormone secretory episodes and in body weight associated with reduced food intake over 24 hours. Central injection of insulin and bovine serum albumin had no such effects. These findings suggest that insulin-like growth factors play a role in growth hormone negative feedback and body weight regulation at the level of the central nervous system.

https://science.sciencemag.org/content/sci/220/4592/77.full.pdf

Insulin-like growth factors: a role in growth hormone negative feedback and body weight regulation via brain.

Preliminary report on a mass screening program for neonatal hypothyroidism.

Clonidine (0.15 mg iv), a selective noradrenergic receptor agonist, increased serum growth hormone (GH) levels (greater than 6 ng/ml) on 8 out of 12 administrations to 6 normal men. This increase was independent of the hypotensive effects of the drug and unrelated to changes in serum cortisol. Clonidine induced a hyperglycemic effect in all subjects which was greatest 15 min after commencint the injection. No changes in blood sugar or GH occurred after placebo injection. Apomorphine, a selective dopamine receptor agonist, elevated GH in each of these 6 subjects (greater than 10 ng/ml). Clonidine had no effect on serum prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), or thyroid-stimulating hormone (TSH). These data are compatible with a dual dopaminergic and noradrenergic mechanism modulating GH secretion in normal men and with the absence of a noradrenergic mechanism in the regulation of PRL, LH, FSH, or TSH.

Effect of clonidine on growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone in the serum of normal men.

Insulinlike growth factor I (IGF-I) has been shown to be a potent mitogen for breast cancer cells in vitro, and IGF-I receptors have been demonstrated on human primary breast neoplasms. In a randomized, placebo-controlled study, we document that administration of the antiestrogen tamoxifen to patients with breast cancer was associated with a statistically significant (P = .002) reduction in the serum level of IGF-I. The mean IGF-I level was 1.4 U/mL in the placebo-treated group and 0.9 U/mL in the tamoxifen-treated group. Because serum IGF-I level is growth hormone (GH) dependent and because data suggest that the pubertal surge in GH and IGF-I levels is sex steroid dependent, we speculate that the mechanism underlying our observation may involve blockade by tamoxifen of estrogen action in the hypothalamic-pituitary axis. We conclude that tamoxifen treatment reduces IGF-I levels and that this reduction may contribute to the therapeutic effect of the drug.

/pdf/effect-of-tamoxifen-on-serum-insulinlike-growth-factor-i-1epb26knat.pdf

Harvey J. Guyda

Papers

Studies of prolactin secretion in human pregnancy.

Insulin-like growth factors: a role in growth hormone negative feedback and body weight regulation via brain.

Preliminary report on a mass screening program for neonatal hypothyroidism.

Effect of clonidine on growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone in the serum of normal men.

Effect of Tamoxifen on Serum Insulinlike Growth Factor I Levels in Stage I Breast Cancer Patients