Human ghrelin is transported across the blood-brain barrier (BBB) of normal mice. Here, we studied the effects of triglycerides, obesity, and starvation in retired breeder mice maintained on a high fat diet, mice age-matched to the retired breeders but maintained on normal chow, and 8 week old mice maintained on breeder chow. The rate of ghrelin transport across the BBB was studied by both the intravenous administration method of multiple-time regression analysis and by the brain perfusion method. We found: 1) obese, aged mice lost the ability to transport intravenously administered ghrelin across the BBB, resulting in an inverse relation between body weight and ghrelin BBB permeability; 2) serum triglycerides promoted transport of intravenously administered ghrelin across the BBB, whereas epinephrine had no effect; 3) fasting tended to promote ghrelin transport across the BBB as most readily shown in brain perfusion studies; 4) evidence suggested that a serum factor promoted ghrelin transport in 8 week old mice. Overall, these results show that serum factors and physiological states influence the rate at which ghrelin is transported across the blood-brain barrier.

CC patients have higher inflammation and lower testosterone, grip strength, functional status, erectile function, fat mass, and appendicular lean body mass. Inflammation, TT, and albumin are associated with heavier symptom burden in this population. Interventional trials are needed to determine whether testosterone replacement and/or antiinflammatory agents benefit cancer patients.

We have observed an association between exposure to a combination of ACEI/ARB + BB and increased survival, decreased hospitalizations, and decreased tumor progression in advanced colorectal cancer. Future studies will be needed to replicate these results and generalize them to broader populations. Determination of causality will require a randomized controlled trial.

Prevalence of hypogonadism in men with cancer has been reported between 40% and 90%, which is significantly higher than in the general population. Hypogonadism is likely to affect the quality of life in these patients by contributing to non-specific symptoms, including decreased energy, anorexia, sarcopenia, weight loss, depression, insomnia, fatigue, weakness, and sexual dysfunction. Pathogenesis of hypogonadism in cancer patients is thought to be multi-factorial. Inflammation may play an important role, but leptin, opioids, ghrelin, and high-dose chemotherapy through different mechanisms have all been implicated as the cause. Hypogonadism is also associated with poor survival in cancer patients. Data looking into the treatment of hypogonadal male cancer patients with testosterone are limited. However, improvements in body weight, muscle strength, lean body mass, and quality of life have been shown in hypogonadal men with other chronic diseases on testosterone replacement therapy. Prospective and interventional trials are needed to test the efficacy and safety of testosterone treatment in improving quality of life of these patients.