Thread: which protocol do u prefer

I really prefer EOD and I use pulse method when using over 4ius.


An Optimum Frequency

Norvartis Foundation Symposium 227, round table discussion between key researchers on the topic of the biological significance of hormonal pulsation


Waxman: You mentioned the frequency encoding of the response. It is clear that if the frequency becomes too rapid and there's insufficient time in the receptor system for resensitization, the result is a reduced effect and ultimately no effect. What happens if you go in the other direction, where frequency becomes distant, and there is a non-physiological long time between pulses? Would you expect to have a loss of responsiveness?

Goldbeter: When the interval between pulses is very large a maximum response is generated by each pulse. However a cell may need to generate a certain number of responses in a given time. ...
...
Hence the probable existence of an optimum interval: if the interval between two pulses is too short, then desensitization ensues; if the interval is too long, the mean intracellular response over time may not be sufficient to establish the desired level of intracllular messenger needed, for example, for gene expression linked to an increased mean level of cAMP.

Waxman: That's interesting, because in the Growth Hormone (GH) system for example, Agneta Mode demonstrated in the early 1980s that twice per day GH treatment given to a hypophysectomized rat, which is much less frequent then the physiological frequency of six or seven times a day, was sufficient to achieve a biological response. In later studies that we carried out, we showed that as we increased the frequency everything was fine until we exceeded - even only slightly - the natural GH pulse frequency, in which case the response was totally lost....

What is lost?

So the question that arises is what is lost? A review of the literature indicates that pulsatile GH appears to invoke continued lipolysis in both obese and lean subjects where as elevations appear not to. While that topic is indeed helpful to us in setting up a protocol because it is fairly definitive.

Both growth hormone pulses and elevations raise paracrine/autocrine IGF-1 mRNA. In fact elevations will raise both systemic and intramuscular paracrine/autocrine IGF-1 mRNA more then pulsation. Is this good, bad or indifferent?

What is GH pulsation, how does it occur & how are pulses amplified?

In general regulation of Growth Hormone (GH) secretion from the anterior pituitary comes from the interplay of two hypothalamic hormones - the stimulator of GH, Growth Hormone Releasing Hormone (GHRH) produced in the hypothalamic arcuate nucleus, and the inhibitor Somatostatin , produced in the periventricular nucleus. Both of these hormones are secreted into the hypothalamic–pituitary portal vasculature in a rhythmic fashion, where they target pituitary somatotrophs which regulate and coordinate GH synthesis and secretion. Direct regulation of GH secretion in the pituitary comes from a patterned release of GHRH and Somatostatin. Indirect regulation comes from somatostatins additional regulation of GHRH-containing neurons in the hypothalamus.

Additionally the gut hormone Ghrelin modulates the actions of both GHRH and Somatostatin. The sum of these interactions seemed to account for the regular rhythm of GH release with high-amplitude GH secretary bursts. However in vitro responses to these various stimuli do not produce the magnitude of highly ordered pulses found in vivo.

In other words, it is convenient for us to think about pulsation as coming from the interplay between GHRH, Somatostatin and Ghrelin but that does not account for the amplitude of pulses. If we go no further in our inquiry we end up with an incomplete understanding of what brings about pulsation.

It is a system that acts in both the GH-releasing pituitary and the Insulin-releasing pancreas and likely in all instances of pulsation throughout the body. A breakdown in this system may lead to diabetes and disordered & inadequate GH pulsation with improper and inadequate signaling on downstream target tissue. As we know, what happens within target cells awaiting hormonal pulses depends on the instruction set received from the pulse. The instruction depends on the shape of the pulse. The duration, magnitude and location of activity/signaling within the target cell triggered by the pulse is dependent on the shape and amplitude of the initiating pulses....


Summary of GH & IGF-1's effect on Energy and Lipid Metabolism

Administration of GH brings about changes in energy and lipid metabolism which result in a reduction in fat mass. GH stimulates resting energy expenditure (REE), lipolysis (mediated by hormone-sensitive lipase), and lipid oxidation. It also reduces uptake of triglyceride into adipose depots by inhibiting lipoprotein lipase.

It appears that some aspects, namely GH-induced increase in lipolysis and lipid oxidation are not sustained in the long-term. Studies seem to show that there is a plateau in loss of fat mass during long-term GH replacement after an initial decrease. Although only partially clarified, it appears that pulsatile patterns of GH are more effective then sustained elevations of GH and that there is more likelihood of a long-term continuation of fat loss. I'm sure we could look at this in many ways, but one way is to realized that it only takes a certain amount of GH over a 2.5 to 3 hour period to maximize GH's contribution to lipolysis and that there is a need for time off or GH troughs to resensitize the pathways that create the effects we desire.
That's the way it may be in regard to chronically elevated GH as it relates to fatloss.

IGF-1 in the short run reduces fat mass in the GH deficient but this positive effect is not sustatined and in fact there is an increase in fat mass with long-term IGF-1 administration. IGF-1 at least in regard to fat loss is better left out of the protocol.
(DatBtrue)