Lessons from growth hormone receptor gene-disrupted mice

Discussion in 'Human Growth Hormone and Peptides' started by Michael Scally MD, May 3, 2018.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

    Growth hormone (GH) is produced primarily by anterior pituitary somatotroph cells. Numerous acute human (h) GH treatment and long-term follow-up studies and extensive use of animal models of GH action have shaped the body of GH research over the past 70 years.

    Work on the GH receptor (R)-knockout (GHRKO) mice and results of studies on GH-resistant Laron Syndrome (LS) patients have helped define many physiological actions of GH including those dealing with metabolism, obesity, cancer, diabetes, cognition and aging/longevity.

    In this review, we have discussed several issues dealing with these biological effects of GH and attempt to answer the question of whether decreased GH action may be beneficial.

    The reports of remarkably low cancer incidence and progression in the GHRKO mouse as well as in LS individuals coupled with human epidemiological studies reporting an increased risk for specific cancers (colorectal, thyroid) in patients with acromegaly collectively offer an indication of the anticancer effects of attenuating GH action.

    In mice and men, the somatotropic axis occupy a central position in the study of aging, healthspan and longevity. GHD mouse models have consistently shown an extended lifespan, while the results are inconsistent in GHD humans. In fact, the GHRKO mouse currently holds the Methuselah Mouse Prize as the world’s longest-lived laboratory mouse, a title awarded by the Methuselah Foundation (Methuselah Mouse ).

    Basu R, Qian Y, Kopchick JJ. MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects? European journal of endocrinology 2018;178:R155-R81. http://www.eje-online.org/content/178/5/R155.full
    mands, ChestRockwell and TRT like this.
  2. TRT

    TRT Member

    So all in all GH long term is not necessarily making people live longer and encourages certain cancers? Or did I read that there were supporting facts of anticancer properties with GH?
    Michael Scally MD likes this.
  3. Rick Kane

    Rick Kane Member

    One of the many reasons I try to keep my IGF levels slightly above the top of the reference range but not too high.
    As I get older I will probably lower my target IGF to somewhere around 250-300.
  4. ChestRockwell

    ChestRockwell Member


    For awhile now it was known that a common variable among all the mutant and transgenic animals that demonstrate increased lifespans is that the reduction in circulating GH and/or igf-1 levels occurs early during the lifespan [67,71,159-162]. It was therefore hypothesized that the disparate effects observed with IGF-1 on healthspan and lifespan are possibly related to the specific period of life in which IGF-1 is suppressed. In contrast, treatment with GH or IGF later in life tends to reverse transgenic models with lengthened life-spans, and is detrimental to the overall aging process [163-166].

    A very thorough comparison of over 30 mice strains provided supporting evidence of this hypothesis, as an inverse correlation with IGF-1 levels at 6 months of age and overall lifespans was observed [167]. Circulating IGF-1 levels rise immediately prior to puberty in both rodents and humans (beginning around day 30 in rodent models). Therefore the levels seen at 6 months of age likely reflect earlier time points identified in those prior studies. One of the potential takeaway points from these studies is that the stage of life when GH and IGF-1 levels are deficient is probably the most important variable in whether or not they impact lifespan [16]. Taking this a step further, one might speculate that low levels of GH/IGF-1 exposure during a short peripubertal period may result in permanent epigenetic modifications within the genome that ultimately affects both healthspan and lifespan.
  5. Very Interesting data. Many of us here push igf-1 levels to well above normal with the intent of promoting growth, hypertrophy specifically, and attaining our individuals goals of size and/or performance. Although it appears logical intuitively that a substance that promotes cell growth could increase our risk of cancer it still remains a 'possibility', a 'hypothetical' at best. We rarely speak here of the risks of excess caloric and protein intake on lifespan and cancer risk even though any of us here looking to add serious muscle mass are forced to consume very large amounts of both.
    ChestRockwell likes this.
  6. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Growth Hormone and Aging

    Role of growth hormone (GH) in mammalian aging is actively explored in clinical, epidemiological, and experimental studies. The age-related decline in GH levels is variously interpreted as a symptom of neuroendocrine aging, as one of causes of altered body composition and other unwelcome symptoms of aging, or as a mechanism of natural protection from cancer and other chronic diseases.

    Absence of GH signals due to mutations affecting anterior pituitary development, GH secretion, or GH receptors produces an impressive extension of longevity in laboratory mice. Extension of healthspan in these animals and analysis of survival curves suggest that in the absence of GH, aging is slowed down or delayed. The corresponding endocrine syndromes in the human have no consistent impact on longevity, but are associated with remarkable protection from age-related disease.

    Moreover, survival to extremely old age has been associated with reduced somatotropic (GH and insulin-like growth factor-1) signaling in women and men. In both humans and mice, elevation of GH levels into the supranormal (pathological) range is associated with increased disease risks and reduced life expectancy likely representing acceleration of aging.

    The widely advertised potential of GH as an anti-aging agent attracted much interest. However, results obtained thus far have been disappointing with few documented benefits and many troublesome side effects. Possible utility of GH in the treatment of sarcopenia and frailty remains to be explored.

    Bartke A. Growth Hormone and Aging: Updated Review. World J Mens Health 2018. Growth Hormone and Aging: Updated Review
    ChestRockwell likes this.
  7. Yes I’ve seen some of this data and while the longevity issues is quite pronounced in the rodent model it is much less so in humans. And in humans with GH excess there is often comorbidities that make it difficult to make comparisons. For those of us that have pushed our igf-1 levels the effects are obvious. The question comes down to how high and how much risk are you willing to take. Many of the contributors here are in fact administering multiple products to enhance performance/physique which further clouds the issue. I for one take care of many people >75 on a daily basis and if this glimpse into the future is any indication of life with longevity....I’ll take the GH, in moderation, and it’s benefits while I’ll can enjoy them. Lifestyle choices make the biggest impact on longevity and disease that we can control. I enjoy the discussion
    ChestRockwell likes this.