hGH - Medical Studies

Krupczak-Hollis K, Wang X, Dennewitz MB, Costa RH. 

Department of Molecular Genetics, University of Illinois at Chicago College of Medicine, Chicago, IL 60607-7170, USA. The Forkhead Box (Fox) proteins are an extensive family of transcription factors that shares homology in the winged helix DNA-binding domain and the members of which play essential roles in cellular proliferation, differentiation, and longevity. Reduced cellular proliferation during aging is associated with a progressive decline in both growth hormone (GH) secretion and Foxm1b _expression. Liver regeneration studies with 12-month-old (old-aged) transgenic mice indicated that increased hepatocyte _expression of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver. GH therapy in older people has been shown to cause an increase in cellular proliferation, but the transcription factors that mediated this stimulation in proliferation remain uncharacterized. In this study, we showed that human GH administration to old-aged Balb/c mice dramatically increased both _expression of Foxm1b and regenerating hepatocyte proliferation. This increase in old-aged regenerating hepatocyte proliferation was associated with elevated protein _expression of Cdc25A, Cdc25B, and cyclin B1, with reduced protein levels of cyclin-dependent kinase inhibitor p27(Kip1) (p27). GH treatment also was found to stimulate hepatocyte proliferation and _expression of Foxm1b protein without partial hepatectomy (PHx). Furthermore, GH treatment of young Foxm1b -/- mice failed to restore regenerating hepatocyte DNA replication and mitosis caused by Foxm1b deficiency. These genetic studies provided strong evidence that the presence of Foxm1b is essential for GH to stimulate regenerating hepatocyte proliferation. In conclusion, our old-aged liver regeneration studies show that increased Foxm1b levels are essential for GH to stimulate hepatocyte proliferation, thus providing a mechanism for GH action in the elderly. 

PMID: 14647066 [PubMed - indexed for MEDLINE] Hepatology. 2003 Dec;38(6):1349-52.

Robert D. Murray, Breeda Columb, Judith E. Adams and Stephen M. Shalet

Department of Endocrinology (R.D.M., B.C., S.M.S.), Christie Hospital, Manchester, M20 4BX, United Kingdom; and Clinical Radiology (J.E.A.), Imaging Science and Biomedical Engineering, The University of Manchester, Manchester, M13 9PT, United Kingdom

Low bone mass is considered a characteristic feature of adult GH deficiency (GHD). Although low bone mass is universally observed in cohorts of GHD adults of young age, the situation is less clear with regard to cohorts of GHD middle-age adults or the elderly. We have examined the relationship between bone mineral density (BMD) and age in 125 severely GHD adults using dual-energy x-ray absorptiometry. This relationship was further examined with a calculated measure of volumetric BMD, bone mineral apparent density (BMAD).

A significant positive correlation was observed between age and BMD (Z scores) at the lumbar spine (r = 0.39, P < 0.0001), femoral neck (r = 0.47, P < 0.0001), total hip (r = 0.47, P < 0.0001), and ultradistal (r = 0.46, P < 0.0001) and distal radius (r = 0.52, P < 0.0001). Young adults were observed to have reduced bone mass, whereas the elderly GHD patients had normal Z scores. After division of the cohort into age ranges (<30, 30 45, 45 60, and >60 yr), BMD Z scores at all five skeletal sites increased significantly across the age groups from youngest to oldest (P < 0.001). When BMD was assessed using absolute values (g/cm2), in contrast to the decline in BMD observed with aging in a normal population, BMD at the total hip and ultradistal and distal radius increased across the age strata of GHD adults (P = 0.003, P = 0.004, and P = 0.002, respectively), and a trend toward an increase in lumbar spine and femoral neck BMD was also observed. No significant change in BMAD was observed across the four age groups. The percentage of patients observed to have BMD Z scores of less than -2.0 at the lumbar spine was 30, 11, 11, and 14% in the four age groups, respectively. At the femoral neck, the corresponding percentages were 36, 6, 7, and 0%, respectively.

In summary, we have shown that the effect of severe GHD on BMD is dependent on age. Low bone mass was observed in the young patients; however, patients over the age of 60 yr demonstrated a mean BMD Z score above that of the reference population and significantly greater BMD (g/cm2) when compared with young GHD adults. Few patients were observed to have BMD Z scores below -2.0 except patients aged less than 30 yr, which, in part, was explained by their shorter stature. Thus, significantly reduced bone mass is not a frequent observation in adults with GHD.

This work was supported by Pfizer UK.

Abbreviations: AO, adult onset; BMAD, bone mineral apparent density; BMD, bone mineral density; CO, childhood onset; DXA, dual-energy x-ray absorptiometry; GHD, growth hormone deficiency; SDS, SD score; SXA, single-energy x-ray absorptiometry.

The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 3 1124-1130
Copyright © 2004 by The Endocrine Society

Testosterone is a hormone produced by the testicles and is responsible for the proper development of male sexual characteristics. Testosterone also regulates the expansion of arteries, promotes the circulation of blood, and is responsible for the maintenance of muscle bulk.

Without adequate production of testosterone, erectile dysfunction, among other problems, can develop. Testosterone replacement therapy may improve erectile dysfunction and other consequences of low testosterone production.

What Causes Testosterone Deficiency?

As a man ages, the amount of testosterone in his body gradually declines. This natural decline starts after age 30 and continues throughout life. Other causes of lowered testosterone levels include:

• Injury or infection to the testicles

• Chemotherapy or radiation treatment for cancer

• Hemochromatosis (too much iron in the blood)

• Dysfunction of the pituitary gland (a gland in the brain that produces many important hormones)

• Inflammatory diseases such as sarcoidosis (a condition that causes inflammation of the lungs)

• Medications, especially those used to treat depression or mental illness and heartburn

• Chronic illness

• Stress

• Alcoholism

What Are the Symptoms of Testosterone Deficiency?

Without adequate testosterone a man may lose his sex drive, have weakened brain and intellectual activity, and may often feel moody. Low levels of testosterone may also result in an increase in stomach and upper body fat, a decline in the amount of muscle in the body, as well as a decline in strength. Bone thinning osteoporosis may also result from low testosterone levels. Other symptoms of lowered testosterone levels include:

• High cholesterol levels

• Depressed mood

• Anxiety

• Problems with concentration and memory

How Do I Find Out if I Have a Testosterone Deficiency?

The only accurate way to detect the condition is to have your doctor measure the amount of testosterone in your blood.

How Can I Increase My Testosterone Level?

If you have low testosterone, your doctor can prescribe testosterone replacement therapy (TRT). Testosterone is available in pill form, patches, injections, or it can be implanted under the skin.

Absorbing testosterone through the skin via a patch or gel, or receiving an intramuscular injection is the best method of delivering TRT. Testosterone in an oral form is not absorbed very well by the body and may increase the risk of high cholesterol and heart and liver problems. Testosterone injections are generally administered every two weeks and can be given either by your doctor or you can learn to give them yourself or teach a family member to give them. Aside from needing to receive a shot every two weeks, the other drawback to injections is that relief from symptoms of low testosterone may be irregular in between shots.

Skin patches effectively deliver testosterone consistently into the body. Depending on the product, these patches can be applied to the scrotum, the buttocks, the arms, or the back. Many men experience mild skin irritation in response to these patches, however the irritation is only rarely severe. Talk to your doctor to determine if TRT is right for you and which mode of delivery would be best.

Who Shouldn’t Take Testosterone Replacement Therapy?

Testosterone replacement therapy can increase cholesterol levels. It can also increase the size of the prostate and if early prostate cancer is present, it can stimulate the cancer’s growth. Thus, TRT may not be right for men who have high cholesterol or other heart disease risk factors or prostate cancer or are at risk for prostate cancer. It is important for all men considering TRT to undergo a thorough prostate cancer screening prior to starting this therapy.

What Are the Side Effects of TRT?

As long as the amount of testosterone given elevates the blood levels to within the normal range, side effects are rare. The following symptoms may indicate that you are receiving too much testosterone and should be brought to your doctor’s attention:

• Nausea and vomiting

• Priapism

• Acne

• Swelling of the ankles

• Headaches

• Noticeably increased appetite

• Breast enlargement

Like any other medication, directions for administering testosterone should be followed exactly as your doctor has ordered. If you are unsure or have any questions about TRT, ask your doctor.