Forskolin may prevent testicular atrophy on cycle by upregulating cAMP

jamezb46

https://pubmed.ncbi.nlm.nih.gov/6685539/

According to this study, micromolar concentrations of the cAMP upregulator forskolin (available as a dietary supplement), was able to lower 10 FOLD the concentration of LH necessary to achieve half-maximal stimulation of androgen production in mouse testes. In other words, the amount of LH needed to achieve an androgen response equal to 1/2 of the maximal response any dose of LH was able to elicit was decimated (literally) by forskolin.

The take away is that if you take compounds for your cycle that still preserve LH to some extent (there is research indicating that DHT derivatives do that), you might be able to get away with keeping testicular function and size on cycle if you take Forskolin.

Obviously that would require that the usual doses of Forskolin as a supplement (250-500 mg/day) can do that. Forskolin is a powerful cAMP upregulator, about 5-7 times as strong as caffeine.

Alternatively, you could take away from this that you could get away with a way smaller dose of hCG on cycle if you choose to run 19-nors or aromatizing compounds like test that crash LH

cs3000

@jamezb46 looked like it had potential with that effect but some other specifics stood out

functional direct effect looks anti androgen, phosphorylates the androgen receptor which = 40% less binding , less activity https://pubmed.ncbi.nlm.nih.gov/9521705/ doesnt say what concentration was used

in humans with mid range test didnt effect test noticeably, slight change but not really (but given as the herb).
https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2005.162

its good for asthma https://pubmed.ncbi.nlm.nih.gov/16749416/

The number of patients who had asthma attacks during the treatment period was significantly lower among those receiving forskolin (8/20, 40%) than among those receiving sodium cromoglycate (17/20, 85%)

jamezb46

@cs3000

According to the first link you posted, forskolin dephosphorylates the androgen receptor, not phosphorylates. There is an increase in the 110 kDa AR isoform and a decrease in the 112 kDa AR isoform. The latter is the phosphorylated isoform.

Specifically, it was with the phosphorylation of serines 641 and 653 that Forskolin interfered.

When the dephosphorylated AR was analyzed in terms of its transcriptional activity, it was observed that the regulation of two genes: PSA and the beta 1-subunit of Na,K-ATPase was inhibited relative to control.

They also claim that the 110kDa AR had only 40% of the maximum ligand binding of the 112kDa phosphorylated AR. I suppose that means that its ligands (androgens) did not bind as effectively to the dephosphorylated AR, thus limiting the amount of gene transcription that androgens could cause relative to interaction with the 112kDa isoform.

Now, that all looks quite troubling, except that the AR has a half life of only a few hours. So, if you take Forskolin, it seems consistent with what we know that the AR that your cells synthesize within a few hours of peak serum levels will be the 110kDa isoform, but that doesn't mean that the next AR that is synthesized will not be the 112kDa isoform.

Increased cAMP also turns on genes associated with ramping up steroid hormone production, so the net outcome is ... who knows

That's why we need people to actually try it and report back. You will never be able to figure out the net effect on paper alone.