Dr. Ron’s Research Review – March 17, 2010

 

This week’s research review has:

            A review article on cortisol and sleep by Tori Hudson, ND

An article on the relationship of testosterone and SHBG with frailty in older men

An article that shows thyroid hormones act indirectly to increase SHBG production

Supplements for immune enhancement in hematologic malignancies

The herbal formulation PHY906 (a 4-herb traditional Chinese medicine formulation) is a potential adjunct to chemotherapy that might become one of the first US Food and Drug Administration (FDA) approved oral herbal medicines for anti-cancer adjunct treatment.

Dr. Ron

 

The cortisol-sleep connection by Tori Hudson, ND

(Hudson 2010) Download

 

Testosterone, sex hormone-binding globulin, and frailty in older men

            (Mohr, Bhasin et al. 2007) Download

OBJECTIVES: To determine whether testosterone (T) levels are associated with frailty or its components. DESIGN: Population-based cohort study conducted in three waves (T1: 1987-1989, T2: 1995-1997, T3: 2002-2004). SETTING: Communities in the Boston, Massachusetts, area. PARTICIPANTS: Six hundred forty-six men aged 50 to 86 at T(3) with complete data on frailty components and hormone measurements. MEASUREMENTS: The frailty phenotype was defined as the presence of three or more of the following: weight loss, exhaustion, low physical activity, slowness, and weakness. Men were classified as frail (> or = 3 components), intermediate (1-2 components), and nonfrail (0 components). Whether total and free T or sex hormone-binding globulin (SHBG) levels were associated cross-sectionally with frailty and with degree of frailty was determined. Potential confounders such as age, chronic disease, lifestyle factors, diet, and physical activity were considered. RESULTS: No association was observed between total or free T and the frailty phenotype after adjusting for confounders. Conversely, a significant association was observed between SHBG and frailty phenotype with an adjusted odds ratio of 1.25 (95% confidence interval=1.06-1.46) per 10-nM increase in SHBG levels. Associations between hormones and degree of frailty were similar to those for overall frailty. Of frailty components, grip strength and physical activity, but not exhaustion, slow walking, or weight loss, were associated with total T levels, whereas SHBG was related to weight loss, exhaustion, and physical activity. CONCLUSION: Total and free T levels were not associated with frailty phenotype, but SHBG was. Furthermore, T and SHBG levels were associated with some, but not all, components of frailty. Therefore, T trials in older men should focus on men experiencing decreases in strength.

 

Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha

            (Selva and Hammond 2009) Download

Thyroid hormones increase hepatic sex hormone-binding globulin (SHBG) production, which is also regulated by hepatocyte nuclear factor-4alpha (HNF-4alpha) in response to changes in the metabolic state of the liver. Since the human SHBG promoter lacks a typical thyroid hormone response element, and because thyroid hormones influence metabolic state, we set out to determine whether thyroid hormones mediate SHBG expression indirectly via changes in HNF-4alpha levels in HepG2 human hepatoblastoma cells, and in the livers of transgenic mice that express a 4.3 kb human SHBG transgene under the control of its own 0.8 kb promoter sequence. Thyroid hormones (triiodothyronine (T(3)) and thyroxine (T(4))) increase SHBG accumulation in HepG2 cell culture medium over 5 days, and increase cellular SHBG mRNA levels. In addition, T(4) treatment of HepG2 cells for 5 days increased HNF-4alpha mRNA and HNF-4alpha levels in concert with decreased cellular palmitate levels. Plasma SHBG levels were also increased in mice expressing a human SHBG transgene after 5 days treatment with T(3) along with increased hepatic HNF-4alpha levels. In HepG2 cells, the human SHBG promoter failed to respond acutely (within 24 h) to T(4) treatment, but a 4-day pre-treatment with T(4) resulted in a robust response that was prevented by co-treatment with HNF-4alpha siRNA, or by blocking the beta-oxidation of palmitate through co-treatment with the carnitine palmitoyltransferase I inhibitor, etomoxir. These data lead us to conclude that thyroid hormones increase SHBG production indirectly by increasing HNF-4alpha gene expression, and by reducing cellular palmitate levels that further contribute to increased HNF-4alpha levels in hepatocytes.

 

Supplements for immune enhancement in hematologic malignancies

            (Sze and Chan 2009) Download

This brief review aims to discuss the various cellular immunological aspects and related mechanisms of the use of specific components from traditional herbal medicines. We begin with lessons learned from thalidomide as an effective single drug with multiple mechanisms of action to treat multiple myeloma. Examples of "supplements" or integrative therapy will be drawn from arsenic trioxide, medicinal mushrooms including Coriolus vesicular and Ganoderma lucidum, followed by the discussion of beta-glucans affecting various immunological important cellular subsets. Different classes of compounds may enhance distinct immune cell populations that might contribute to a multi-targeted holistic effects on anti-cancer treatment. Finally, we conclude by highlighting an herbal formulation PHY906 as a potential adjunct to chemotherapy that might become one of the first US Food and Drug Administration (FDA) approved oral herbal medicines for anti-cancer adjunct treatment.

 


References

Hudson, T. (2010). The cortisol-sleep connection. Women's Health E-mail Update March 2010, Emerson Ecologics.

Mohr, B. A., S. Bhasin, et al. (2007). "Testosterone, sex hormone-binding globulin, and frailty in older men." J Am Geriatr Soc 55(4): 548-55.

Selva, D. M. and G. L. Hammond (2009). "Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha." J Mol Endocrinol 43(1): 19-27.

Sze, D. M. and G. C. Chan (2009). "Supplements for immune enhancement in hematologic malignancies." Hematology Am Soc Hematol Educ Program: 313-9.