the feedback loop whereby igf-i acts on gh production at the pituitary is a strange one. apparently each cell has its own on/off switch, so it's either all or nothing, *but* the point at which this switch varies widely from cell to cell.
http://mend.endojournals.org/cgi/content/full/15/9/1549
"Quantification of the average endogenous GH mRNA level was performed by RPA on MtT/S cultures to which increasing concentrations of LR3IGF-1 or IGF-I were added (Fig. 4). Analysis by one-factor ANOVA showed that the amount of GH mRNA in MtT/S cells treated with increasing concentrations of LR3IGF-1 was significantly reduced (F7, 16 = 13.4, P = 0.0001; Fig. 4A). Treatment with as little as 0.004 nM LR3IGF-1 significantly reduced GH mRNA levels vs. controls (P < 0.05), and 2.6 nM LR3IGF-1 maximally reduced GH mRNA levels."
note that 2.6nM LR3IGF-I is a concentration not far greater than we're likely to reach in practice: given a molar weight of 7.6kDa, it corresponds to 19.7ng/ml. 50mcg in one shot would likely lead to peak serum levels around 10nm/ml in your average bodybuilder. it's also important to consider that the binding proteins are heavily involved in aggregating/keeping/liberating IGF-I in many tissues, and some actually increase its bioactivity. this will lead to unpredictable effects of lr3igf-i on various systems, including the pituitary.
the serum half-life is probably on the order of 14 hours, but the important thing is how long it's active in tissues for. the reduced affinity for binding proteins probably reduces this duration considerably, but how much in vivo pituitary? dunno.
regarding the use of hgh/igf-i in combination, it's likely that using them at once would decrease their combined effectiveness:
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=15749813
"Receptor mRNA expression was altered by exposing cells to GH or IGF-I. GH and IGF significantly decreased GHR mRNA in proliferative cells. GH and IGF also decreased IGF-IR mRNA in resting cells and the 2- and 4-week-old proliferative and hypertropic cells. Treating cells in culture with GH increased the number of apoptotic cells across all ages and zones."
i.e. in that tissue at least, GH and IGF downregulate each other's receptors as well as their own.
it is worth noting that the igf-i produced in an autocrine manner by skeletal muscle in response to damage from training is a different IGF (IGF-IEb), a.k.a. MGF, than that produced in response to GH (IGF-IEa). LR3IGF-I is much closer in structure and action to IGF-IEa. GH will not directly upregulate MGF production, but may in the presence of exercise. whether systemic IGF-I will is debatable, but it doesn't strike me as likely, so you may see some synergy(and greater potency of GH as compared to IGF-I or even combined use) from this aspect. there is unfortunately very little research here.
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=14565994
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=15308683
but the science is just the science; what matters most is the real-world experience. i've never run gh, though i swear by lr3igf-i. has anyone here run them together versus each apart? what was your experience like?
http://mend.endojournals.org/cgi/content/full/15/9/1549
"Quantification of the average endogenous GH mRNA level was performed by RPA on MtT/S cultures to which increasing concentrations of LR3IGF-1 or IGF-I were added (Fig. 4). Analysis by one-factor ANOVA showed that the amount of GH mRNA in MtT/S cells treated with increasing concentrations of LR3IGF-1 was significantly reduced (F7, 16 = 13.4, P = 0.0001; Fig. 4A). Treatment with as little as 0.004 nM LR3IGF-1 significantly reduced GH mRNA levels vs. controls (P < 0.05), and 2.6 nM LR3IGF-1 maximally reduced GH mRNA levels."
note that 2.6nM LR3IGF-I is a concentration not far greater than we're likely to reach in practice: given a molar weight of 7.6kDa, it corresponds to 19.7ng/ml. 50mcg in one shot would likely lead to peak serum levels around 10nm/ml in your average bodybuilder. it's also important to consider that the binding proteins are heavily involved in aggregating/keeping/liberating IGF-I in many tissues, and some actually increase its bioactivity. this will lead to unpredictable effects of lr3igf-i on various systems, including the pituitary.
the serum half-life is probably on the order of 14 hours, but the important thing is how long it's active in tissues for. the reduced affinity for binding proteins probably reduces this duration considerably, but how much in vivo pituitary? dunno.
regarding the use of hgh/igf-i in combination, it's likely that using them at once would decrease their combined effectiveness:
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=15749813
"Receptor mRNA expression was altered by exposing cells to GH or IGF-I. GH and IGF significantly decreased GHR mRNA in proliferative cells. GH and IGF also decreased IGF-IR mRNA in resting cells and the 2- and 4-week-old proliferative and hypertropic cells. Treating cells in culture with GH increased the number of apoptotic cells across all ages and zones."
i.e. in that tissue at least, GH and IGF downregulate each other's receptors as well as their own.
it is worth noting that the igf-i produced in an autocrine manner by skeletal muscle in response to damage from training is a different IGF (IGF-IEb), a.k.a. MGF, than that produced in response to GH (IGF-IEa). LR3IGF-I is much closer in structure and action to IGF-IEa. GH will not directly upregulate MGF production, but may in the presence of exercise. whether systemic IGF-I will is debatable, but it doesn't strike me as likely, so you may see some synergy(and greater potency of GH as compared to IGF-I or even combined use) from this aspect. there is unfortunately very little research here.
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=14565994
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=15308683
but the science is just the science; what matters most is the real-world experience. i've never run gh, though i swear by lr3igf-i. has anyone here run them together versus each apart? what was your experience like?