[Lotus]

Hi Lotus,

Thank you for this super informative thread! My cycle is usually around 35 days when not taking BCP, and my program contains BO, mk677, fish oil, WP, Reishi, and MSM. I'm ordering aloe vera and vitamin D3 after reading your post " alt="" title="">

I had a question that I hope you can shed some light on  " alt="" title="">

Can you source the paper on mk-677 inhibiting growth hormones? In this graph it seems that ibutamoren takes a few months to work but it increases both GH and IGF-1 

Hi nwyori, you're welcome.

To be honest I don't think MK-677 is relevant for NBE, meaning it hasn't produced any results. Though using exogenous IGF-1 type agents in general turns off GH signaling from what's called the negative feedback loop, simply put, once MK-677 reaches circulation its benefits are blocked at the HPA axis (hypothalamus/pituitary axis) via stimulation of somatostatin. It could be possible though to inhibit somatostatin in relation to MK-677. I wish people would stop using it and recommending it for NBE.

I have a better way to stimulate IGF-1, and it starts with stimulating the pituitary via the cAMP pathway. And actually Forskolin stimulates the pituitary, and along with stimulating GH secretion it stimulates estrogen via aromatase, and how forskolin stimulates the pituitary is from TRH (thyroid releasing hormone production). 

Though forskolin is inhibited (degraded) by PDEs (Phosphodiesterase), but...I know a way around the inhibition, and I'll explain this process in a follow up to this post. 

I would go after HGH during sleep, I'll make a follow up post covering this. 

Activating the cAMP pathway stimulates GH

Insulin-like Growth Factor I (IGF-I) inhibits GH secretion by a negative loop at both hypothalamic and pituitary levels.

In pituitary cells, Gs (G proteins) plays a central role in mediating cAMP pathway activation after stimulation by hormones, such as growth hormone (GH) and corticotroph-releasing hormone (CRH).

Dopamine and somatostatin inhibit forskolin-stimulated prolactin and growth hormone secretion but not stimulated cyclic AMP levels in sheep anterior pituitary cell cultures 

K P Ray et al. Mol Cell Endocrinol. 1986 May. 

Abstract 

Forskolin, an activator of adenylate cyclase, has been used to investigate the effects of raising pituitary cell cyclic AMP concentrations on prolactin and growth hormone secretion and to examine the role of cyclic AMP in the inhibitory actions of dopamine and somatostatin. Incubation of cultured ovine pituitary cells with forskolin (0.1-10 microM; 30 min) produced a modest dose-related increase in prolactin release (120-140% of basal) but a much greater stimulation of growth hormone secretion (170-420% of basal). Cellular cyclic AMP concentrations were only increased in the presence of 1 and 10 microM forskolin (2-5.5 times basal). A study of the time course for forskolin (10 microM) action showed that stimulation of prolactin (1.5-fold) and growth hormone (4.7-fold) secretion occurred over 15 min; subsequently (15-60 min) the rate of prolactin secretion from forskolin-treated cells was equivalent to that measured in controls, while growth hormone release remained elevated. Cellular cyclic AMP concentrations were also rapidly stimulated by forskolin (10 microM); they reached a maximum (12 times control) within 15 min, and then declined (15-60 min) but remained elevated relative to those in untreated cells (4.9 times control at 60 min). Dopamine (0.1 microM) inhibited basal secretion of both prolactin and growth hormone. In the presence of forskolin (0.1-10 microM), dopamine (0.1 microM) inhibited prolactin secretion to below the basal level and considerably attenuated the stimulation of growth hormone secretion. Similarly, somatostatin suppressed both basal and forskolin-induced prolactin and growth hormone secretion. However, neither dopamine nor somatostatin significantly decreased the stimulatory effect of forskolin on cellular cyclic AMP accumulation.(ABSTRACT TRUNCATED AT 250 WORDS) 

cAMP in the pituitary: an old messenger for multiple signals
https://jme.bioscientifica.com/view/journals/jme/52/1/R67.xml

Antibody experiments (1) have clearly shown that basal GH levels are elevated when somatostatin is neutralized. 

Somatomedin C has also been implicated in the negative feedback regulation of GH, at least partially by stimulating release of somatostatin (5). 
https://link.springer.com/chapter/10.100...-7886-4_18

Negative feedback regulation of pulsatile growth hormone secretion by insulin-like growth factor I. Involvement of hypothalamic somatostatin 

M Bermann et al. J Clin Invest. 1994 Jul. 

Free PMC article 

Abstract 

To investigate the mechanisms of the negative feedback inhibition of growth hormone (GH) secretion by IGF-I, we studied parameters of GH pulsatility in six normal, fed men before and during a 48-h infusion of recombinant human IGF-I (rhIGF-I) (10-15 micrograms/kg per h). Plasma levels of IGF-I increased from the baseline value of 163.5 +/- 9.3 micrograms/liter (mean +/- SE) to a new steady state of 452.0 +/- 20.9 micrograms/liter during the infusion. Plasma GH concentrations were measured every 10 min for 24 h during both saline and rhIGF-I infusions using a sensitive chemiluminescent assay. Overall, GH concentrations were suppressed during the rhIGF-I infusion by 85 +/- 3%, mainly by attenuating spontaneous GH pulse amplitude (77 +/- 4% suppression). The apparent GH pulse frequency was attenuated from 7.8 +/- 0.9 to 4.7 +/- 0.6 pulses/24 h (P = 0.006). Administration of rhIGF suppressed GH responses to exogenous GH-releasing hormone by 82 +/- 3%, and thyroid-stimulating hormone responses to thyrotropin-releasing hormone were also suppressed by 44 +/- 9%. This constellation of hormonal effects is most compatible with the rhIGF-I-induced stimulation of hypothalamic somatostatin secretion. 
https://pubmed.ncbi.nlm.nih.gov/7913710/