Adapted from Cuneo RC, Salomon F and PH Sönksen. The syndrome of growth
hormone deficiency in adults. In Anders Juul and Jens O.L. Jorgensen, eds.
Growth Hormone in Adults: Physiological and clinical aspects. New York:
Cambridge University Press, 1996; 145-167.
Factors that Influence GH
Obesity diminishes pulsatile secretion of GH. It also causes
accelerated breakdown of GH by the body. On the other hand, sustained
high-intensity exercise increases the quantity and number of pulses of GH
release. Intense is the key word here; garden-variety jogging won't do it.
Fasting increases both the pulsatile frequency and the amount of GH
secreted. Eating shuts it down by stimulating insulin, which opposes GH.
Over the long term, a poor diet can tremendously interfere with proper GH release and IGF-1 formation. The correct diet will
assist in overcoming excess insulin in order to promote growth hormone. In
chapter six we will detail diet and exercise routines that will help to
optimize your GH release and response.
Testosterone, estrogen, and other hormones enhance GH secretion. The
synergistic effect of replacing a variety of deficient hormones cannot be
overstated. Results in this area are enhanced with the use of the proper
forms of these hormones that are recognized by the body. In chapter seven
we offer some guidelines for understanding the role that various hormones
play in GH management.
The amino acids L-arginine and ornithine can cause GH release if taken
in high enough amounts. Certain drugs also cause GH release, including
L-dopa and clonidine. In chapters three and four, you will gain some
insight to the complexity and function of GH secretagogues.
The liver synthesizes insulin-like growth factors (IGF-1 and 2) as part
of a feedback loop that regulates GH.
The relationship between GH and IGF-1 is extremely complex. Binding
proteins and GH receptors are involved in how GH affects the body. African
pygmies are a living example of the importance of GH receptors. One would
think that giving pygmies GH would make them grow, but it doesn't. Pygmies
have plenty of GH, but they are lacking receptor sites on their cells.
Later, you will learn how to optimize IGF formation and sensitize GH and
IGF-1 receptor sites in order to optimize response to GH therapy.
Treatment in the Early Days
From 1958 until the time it was finally synthesized, GH was
painstakingly extracted from human cadavers and injected into GH-deficient
children and adults. Heat was known to destroy this precious substance, so
in the early days of GH treatment the extract could not be heated to the
point of killing all contaminants. Consequently, some of the early GH
batches, which came from people who harbored the catalyst for the human
version of "mad cow" disease, were contaminated. Creutzfeldt-Jakob disease
(CJD), as it is known, is a horribly debilitating brain disorder for which
there is no known cure. CJD belongs to a family of diseases that afflict
sheep, cows and humans. The prion that causes it is neither viral nor
bacterial, but is thought to be a normal protein. that has become
distorted. Prion contamination ceased
to be a problem when the FDA banned the natural version of GH and approved
the synthesized version in 1985.
Synthetic GH Arrives
During the early 1980s, two phenomena occurred that would eventually
lead to synthetic human GH; no longer would it have to be taken from
cadavers. Yuppie fever hit, and DNA cloning was invented. Cloning allowed
researchers, for the first time, to ferret out the individual sequences of
DNA that code for proteins. The discovery of cloning techniques has fueled
a scientific revolution that is still in its infancy. "Recombinant DNA"
technology allows DNA to be snipped into little pieces with "molecular
scissors" and placed into bacteria. The bacteria then chum out little
Xerox copies of the snippet. By amplifying DNA in this fashion, it becomes
possible to really study and understand individual sequences. This is how
the DNA sequence that codes for GH was found. The first product of this
method offered on a commercial scale was insulin. The second was GH. The
same company, Genentech, synthesized both of them.
The large scale cloning of human GH had come about in large part
because of the actions of congress, which, in 1983, wrote The Orphan Drug
Act into law. The law was designed to provide incentive for drug companies
to develop and market drugs that would help people with rare diseases.
Many of these people were falling through the cracks because drug
companies could not justify spending money to develop drugs for which
there wasn't a large market. The law provided that the federal government
would heavily subsidize the development of drugs that affected 200,000 or
fewer people, and any drug company that took on the task would have a
7-year monopoly on the market.
Genentech wasted no time in applying for "Orphan" status for the
development of GH. The "orphan" market for GH was 7,000 GH-deficient kids.
These children have severely inhibited growth, a condition that doctors
refer to as "hypopituitary dwarfism". By 1985, Protropin was FDA approved
for hypopituitary dwarfism. Initial sales were estimated to be $4M.
One might wonder.. Why would the biotech darling of Wall Street go after a
market comprised of only 7,000 children? GH, like insulin, has to be taken
every day for life. With the monopoly provided by the Orphan Drug Act,
there would be no competitive pricing. The company holding the monopoly on
GH could name their price.
At $15,000 per child per year-the price Genentech decided on-the $4M
market for GH quickly turned into an $150M market. By the third quarter of
the first year Protropin was on the market, it raked in $23M. In 1987,
Adelle Haley, financial Sialyst at Smith Barney, declared that "short
stature is a small market". According to her, Protropin sales wouldn't go
above $23.8M. Her financial soothsaying proved to be wrong. Protropin
ended the year with $43.6M in sales. The following year, sales were at
$86M, and by 1989 sales were $122M. In 1995 Genentech was predicting sales
of $lB worldwide.
YUPPIES, Lawsuits, and the Government
Genentech got a big boost in sales by a social phenomenon. About the
same time that Genentech hit the market with growth hormone, YUPPIE fever
gripped America. The credo of YUPPIE Dom was all the perfection money can
People with short kids soon found out that perfection could be bought for
about $15,000 a year. The number of children diagnosed with hypo pituitary
dwarfism (the only condition for which GH was approved) rose to 15,000 in
1989, from the original 7,000 in 1985. By 1995, 30,000 children per year
were diagnosed with it. Company spokesmen attributed the increase to
enhanced diagnostic abilities on the part of pediatricians. The whole
thing was out of control during the '80s. Jeremy Rifkin's anti-biotech
group sued the National Institute of Health (NIH) to stop trials of GH on
short kids, and the FDA and Congress launched an investigation of
Genentech's promotion of the drug.
The pharmaceutical giant, Eli Lilly, wanted GH too. It successfully
cloned GH a few months after Genentech, and called its version Humatrope.
As far as Genentech was concerned, it was fine to clone Humatrope. It was
not fine to put it on the market.
Despite Genentech's "orphan" protection, the FDA approved Humatrope in
1987. Genentech promptly sued the FDA.
In September of 1987, the first of its claims were shot down in a federal
court. This was not the end of the litigation, however. In all, five
companies went after GH and each other. Both Hoffmann-LaRoche and Lilly
ended up suing Genentech, and Genentech sued them back over patent rights.
Lilly and Genentech wrangled in court for 8 years,
with Lilly finally throwing in the towel, agreeing to pay Genentech at
least $145M over several years.
Even as Genentech went to market with Protropin, the company knew it
could be used for a lot more than just dwarfism. Before Genentech made the
synthetic version, athletes-notably Olympic athletes-were injecting GH
It was widely believed in the athletic community that GH could increase
endurance and strength. This "underground" use of GH by athletes was
problematic in two significant ways. First, pharmacological (as opposed to
physiological) doses of GH were being used, secondly, the long term
effects were unknown. A pharmacological dose is one that far exceeds
levels that would occur naturally in the body. A pharmacological dose is
designed to act like a drug on the body's systems. This is far different
from the physiological doses being injected into kids to make them grow. A
physiological dose merely brings levels up to normal. No one -including
the athletes themselves- knew what the side effects of huge doses of GH
would be. Because the natural hormone was undetectable, policing it was
Publicly, Genentech admitted that GH might be used for enhanced wound
healing. Osteoporosis was a maybe. But the scientific literature contained
tantalizing hints that the market for GH would be huge. Growth hormone
affects many systems of the body; in fact, it targets nearly all tissues.
The insulin like effect of GH that results in lowering of blood glucose
made it a very attractive target for diabetes research. In addition, GH
was known to be "lipolytic" (fat burning). From the drug company's
perspective, the fat-lowering, sugar-lowering capability of GH gave it an
exciting and potentially huge market.
Hundreds of studies later, GH has become one of the most exciting
hormones ever studied. The anti-aging potential is so great that the
National Institute on Aging is conducting long-term, large-scale studies.
There is nothing to suggest that GH won't live up to its reputation.
Unlike other hormones with anti-aging potential, GH has been extensively
studied in humans. The scientific literature is replete with new studies.
GH has been associated with improvement in some of the most prevalent and
intractable diseases of aging: Parkinson's disease, osteoporosis, heart
disease and diabetes.
And the good news is that people don't have to travel to Anterea to get
it. It's available here -on earth.
I'm so excited about Symbiotropin. I have lost 30 inches in three
months, it has burned the cellulite very fast off my legs and hips. The
next best thing is my skin. My skin was so thin it was tearing almost
daily... it is now thick again, it looks and feels like when I was much
younger!! My age spots have disappeared from my hands... my eyes have
improved so much I seldom wear my glasses anymore... I have increased my
muscle mass and strength tremendously. My memory has really improved also.
My hair is thicker and grows really, really fast...
-H.G. (Female, Age 57)