Friday, March 19, 2010

Gigantism: Tissue Sensitivity to Growth Hormone

Gigantism is more than just elevated levels of Growth Hormone.  There are tons of incidents where people have low or normal levels of Growth Hormone with Gigantism.  Extremely high levels of HGH may increase the number of Growth Hormone Receptors but the pathology of Gigantism is likely to be far more complex.

Evidence that Sensitivity to Growth Hormone (GH) Is Growth Period and Tissue Type Dependent: Studies in GH-Deficient lit/lit Mice

"Overexpression of GH in erythroid cells using ß-globin promoter increases bone size and BMD in transgenic mice"

Transgenic refers to the altering of genes. This B-globin promoter could be useful to us because it did increase bone size.

An explanation of what a lit mice is:
"For our studies, we used lit/lit mice as a model because we predicted that these mice with no detectable endogenous GH levels should respond to exogenous GH much more robustly compared with wild-type mice with normal endogenous GH levels."

Remember these mice are GH deficient so they were already unlikely to reach their height potential and GH may have only given them a boost towards their original height potential.

Groups 1 and 2 were prepubertal, 3 and 4 were pubertal; 5 and 6 were postpubertal; 7 and 8 were fully adult mice.

"Our findings also reveal that GH administration during the prepubertal growth period has little effect on general body growth or on bone accretion. This conclusion is based on the findings that the magnitude of increase in body weight was much smaller when GH was administered between d 7–21 compared with between d 21–34 (< 20% vs. 70%) and that overall changes in many of the parameters studied were similar in mice treated with GH between d 7 and 34 vs. have recently reported that the skeletal deficit is minimal in GH-deficient lit/lit mice compared with control mice at the end of the prepubertal growth period. If these findings can be extrapolated to humans, this would suggest that GH administration during the prepubertal growth period might not be efficacious[efficient] compared with pubertal or postpubertal growth periods in GH-deficient children."

This gives us an important clue perhaps there is something that occurs during puberty that increases sensitivity to Growth Hormone.  You'd expect HGH to still increase height prepuberty by at minimum increasing IGF-1 mediated chondrocyte hypertrophy.  The study did find that HGH mediated IGF-1 increased more post-puberty than pre-puberty.  Maybe pre-puberty the bone relies more on IGF-2. 

The exercise-induced growth hormone response in athletes.

"Human growth hormone (hGH) is secreted in a pulsatile fashion[Altering this pulsatile fashion may be one way to alter height], generally following a circadian rhythm. A number of physiological stimuli can initiate hGH secretion, the most powerful, non-pharmacological of which are sleep[maintaining a regular circadian rhythm is vital for height growth until we know how manipulating the pulses of HGH secretion can manipulate height] and exercise. hGH has many varied roles throughout life, from growth itself, including the turnover of muscle, bone and collagen, to the regulation of selective aspects of metabolic function including increased fat metabolism and the maintenance of a healthier body composition in later life. The exercise-induced growth hormone response (EIGR) is well recognised and although the exact mechanisms remain elusive, a number of candidates have been implicated. These include neural input, direct stimulation by catecholamines, lactate and or nitric oxide, and changes in acid-base balance. Of these, the best candidates appear to be afferent stimulation, nitric oxide and lactate. Resistance training results in a significant EIGR. Evidence suggests that load and frequency are determining factors in the regulation of hGH secretion. Despite the significant EIGR induced by resistance training, much of the stimulus for protein synthesis has been attributed to insulin-like growth factor-1 with modest contributions from the hGH-GH receptor interaction on the cell membrane. The EIGR to endurance exercise is associated with the intensity, duration, frequency and mode of endurance exercise. A number of studies have suggested an intensity 'threshold' exists for EIGR. An exercise intensity above lactate threshold and for a minimum of 10 minutes appears to elicit the greatest stimulus to the secretion of hGH. Exercise training above the lactate threshold may amplify the pulsatile release of hGH at rest, increasing 24-hour hGH secretion. The impact of chronic exercise training on the EIGR remains equivocal. Recent evidence suggests that endurance training results in decreased resting hGH and a blunted EIGR, which may be linked to an increased tissue sensitivity to hGH[increased tissue sensitivity to HGH is way more important increased HGH levels as you can increase HGH easily through other means; thus endurance exercise is good for height growth]. While the potential ergogenic effects of exogenous GH administration are attractive to some athletes, the abuse of GH has been associated with a number of pathologies. Identification of a training programme that will optimise the EIGR may present a viable alternative. Aging is often associated with a progressive decrease in the volume and, especially, the intensity of exercise. A growing body of evidence suggests that higher intensity exercise is effective in eliciting beneficial health, well-being and training outcomes. In a great many cases, the impact of some of the deleterious effects of ageing could be reduced if exercise focused on promoting the EIGR. This review examines the current knowledge and proposed mechanisms for the EIGR, the physiological consequences of endurance, strength and power training on the EIGR and its potential effects in elderly populations, including the aged athlete."

Marathan runners are not super tall.  Marathan Runners are the kings of endurance training.  If endurance training can increase height by increasing the number of Growth Hormone Receptors then you'd expect marathon runners to be very tall.  Maybe Growth Hormone Receptors don't increase height that much.

Gender Differences in the Effects of Long Term Growth Hormone (GH) Treatment on Bone in Adults with GH Deficiency

"In the present study we observed increases in BMD and BMC at different measurement sites during long term treatment with rhGH in patients with hypopituitarism(a pituatary that does not secrete enough growth hormone). The male patients with GHD gained more from the long term GH treatment with regard to bone mass despite receiving significantly lower doses of rhGH than the women. Furthermore, there were sustained increases in serum markers of bone metabolism and in serum IGF-I; these changes were similar in the men and women despite the difference in rhGH dose."

For possible explanations the study states: "In castrated rabbits the expression of GH receptor messenger ribonucleic acid in both the liver and the growth plate has been reported to be increased by testosterone and decreased by estradiol[The response to Growth Hormone may be based on the presence of sex organs]. This could be a mechanism responsible for the gender difference in the serum IGF-I response to GH treatment and could be of relevance for the present finding of a greater gain in bone mass in the GHD men. On the other hand, in rats estradiol has been found to stimulate GH receptor expression, and testosterone did not influence GH-induced IGF-I expression. Osteoblasts contain receptors for both androgens and estrogens, and in bone cells, estradiol stimulated GH receptor expression. "

Estradiol is an estrogen sex hormone.  Estrogen does have height increasing effects up to a certain point.  Estrogen may increase the number of growth hormone receptors and this can result in increased height until the other effects of estrogen kick in. Also, given the castration effect estrogen may decrease height in females and increase height in males.

Gigantism is likely not caused by an increase in tissue sensitivity to growth hormone.  As then endurance athletes would be incredibly tall unless the sensitivity occurs only in the muscle and not the bone.  But, endurance running also is taxing on the bones as well.  You can get lactic acid in the muscles but not the bones so if the increase in GHR is based on that it would explain the lack of height.  However, Nitric Oxide can build up in the bones as well as the muscle.  So unless the increase in GHR is caused by lactic acid, more Growth Hormone Receptors likely cannot cause Gigantism.

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