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Testosterone Opposes IGF-1 Feedback in Older Men

E-Newsletter No. 68

Growth hormone, like all other hormones, is essential for life. Then why does it decline as we age? Life is a finite concept.  In other words we are all programmed to self-destruct. This is what the aging process is all about.  And, aging begins at the time of conception.  In fact, we age more during those nine months of gestation than at any other time during our entire life after we leave our mother’s womb.  The formation of cells and organs needed to sustain life at birth uses up more than two-thirds of the protective telomeres wrapping the end our chromosomes. Telomeres are necessary to keep chromosomes from unraveling when they divide to form new cells. When chromosomes unravel, new cells cannot be formed, and the decline of aging occurs. (Think of the plastic on the ends of your shoelaces used to keep them from unraveling.)

Normal growth ends after we reach the age of reproduction. After puberty, aging proceeds in an ever accelerating rate. In other words, “Mother Nature has no use for us after we reach the age of reproduction.” Our sole purpose in life is procreation. The egg is all important. Life is secondary.

Now, let us go back to the subject of Growth hormone. Growth hormone (GH) secretion rates decrease by as much as 50% every 7 years, after age 18 in men. The causal mechanisms are unknown. (GH) is released from the pituitary gland in pulses 6 to 8 times per day.

This is controlled by two hormones from the master gland in the brain called the hypothalamus located just above the pituitary. These two hormones have counter-regulatory actions. One, GH-releasing hormone stimulates the pituitary to release GH. The other, Somatostatin, provides a feedback mechanism to the pituitary in response to the presence of secreted GH by inhibiting further release of GH.

Here's the take home point to this article:
Most of the peripheral growth promoting actions of GH are provided by insulin-like growth factor 1 (IGF-1). GH-dependent IGF-1 is secreted predominantly in the liver, and participates in feedback regulation of GH gene transcription and secretion. But, in older men IGF-1 suppresses GH-releasing hormone’s stimulatory effects, whereas, testosterone doubles pulsatile GH secretion.

Note: Testosterone should only be used under the guidance of a qualified endocrinologist! 

See these articles for information on the very negative effects of inappropriate testosterone administration: 
37) Testosterone: the Good, the Bad, and the Ugly
48) Hormone Updates-New Findings On Estrogen & Testosterone

A group of scientists led by Johanness D. Veldhuis, MD., at Mayo Clinic in Rochester, Minn., hypothesized that testosterone supplementation can relieve IGF-1’s negative feedback effect in healthy older men.

The team gave 24 healthy men, aged 50-75 years, saline or recombinant human IGF-1, in random order, at 1.0, 1.5, and 2.0, mg/m2, after overnight fasting. The men were then prospectively randomized to receive either placebo or 175 mg of testosterone enanthate every 6 days for three doses. 

The team reported, as expected, IGF-1 administration increased mean and peak IFG-1 concentrations and suppressed 8-hr mean GH concentrations at all 3 doses. Testosterone administration significantly opposed this suppression compared with placebo. Similarly, IGF-1 repressed pulsatile GH secretion in a dose-dependent manner, and testosterone opposed IGF-1’s submaximal (1.0 mg/m2) but not its maximal inhibition. IGF-1 injections also significantly lowered basal GH secretion. Testosterone did not reverse this effect.

The scientists concluded that “dissecting the precise network of signals involved in the opposing actions of testosterone and IGF-1 will require further studies,” but, say their data indicate that systemic testosterone supplementation “can selectively amplify GH secretion and oppose IGF-1 feedback in aging men. (1.)

Additionally, from another recently reported study, there is evidence about boosting GH levels in young adults: Both continuous and intermittent exercise increased 24-hour GH secretion. A single 30-minute and three 10-minute bouts of physical activity increased 24-hour integrated serum growth hormone concentrations equally in young adults.

These data suggest that both continuous and intermittent exercise may be beneficial in promoting increases in 24-hour GH secretion in obese and non obese individuals, according to researchers at the University of Virginia and Mayo Clinic in Rochester.

"When sedentary or obese individuals start an exercise program they may have difficulty completing one 30-minute bout of exercise. The ability to spread the bouts of exercise throughout the day allows individuals to complete the exercise with similar benefits and without the sense of discouragement that might occur if the individual cannot complete 30 minutes of continuous exercise.” (2.) 

(1.)Veldhuis JD, Keenan DM,Bailey JN, et al. Testosterone supplemention in older men restrains insulin-like growth factor’s dose-dependent feedback inhibition of pulsatile GH secretion. J Clin Endocrinol Metab 2009 94:

(2.)Whitman,A. J Clin Endocrinol Metab. 2008;93:4711-4720.

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