Understanding dopamine (agonist) in regulating GH secretion

[NFRCR]

This is what is known right now about dopamine and dopamine agonists in terms of regulating GH secretion.

In hypothalamus.

• Increases GHRH release.
• Inhibits Somastostatin release.

In pituitary:

• Inhibits GH release in response to GHRH.

The above is based on these articles. It applies to dopamine and all dopamine agonists - bromocriptine, pramipexole, L-dopa (dopamine precursor) etc.

I am trying to understand when exactly does dopamine start inhibiting GH secretion in pituitary. Can this happen to a subject without acromegaly as well?

Is it constant dopamine stimulation (in contrast with dopamine pulses) that results inhibition of GH release in pituitary?

Alternatively, is it dependent in the sensitivity of dopamine receptors in pituitary? It is hypothesized high GH concentration increases this sensitivity and therefore causes dopamine to have an inhibitory effect. This is why most subjects with acromegaly show a decrease in GH levels.

Role of dopamine in the regulation of growth hormone secretion: dopamine and bromocriptine augment growth hormone (GH)-releasing hormone-stimulated GH secretion in normal man.

The role of the dopaminergic system and its interaction with GH-releasing hormone (GHRH) in the regulation of GH secretion was investigated in normal men in two complementary studies. The men were given continuous iv infusions of 0.15 M saline (5 h), dopamine (4 micrograms/kg X min; 1 h), GHRH (2 ng/kg X min; 2 h), and GHRH (2 ng/kg X min; 2 h) plus dopamine (4 micrograms/kg X min; 1 h) on four separate occasions, and serum GH responses were measured. In a second study, on separate days, placebo or bromocriptine (2.5 mg/dose) was administered, and GH and PRL responses to a single iv GHRH dose were measured. A continuous infusion of dopamine and GHRH on separate days stimulated GH secretion in all subjects. The mean integrated GH secretion was 13.2 +/- 3.1 (+/- SEM) ng/mL X h during the dopamine infusion and 14.7 +/- 4.6 during GHRH, compared with 1.7 +/- 0.4 during the saline infusion. The combination of GHRH and dopamine resulted in the greatest stimulation of GH secretion (29.8 +/- 5.7 ng/ml X h; P less than 0.05 vs. 3 other study days). The oral dopamine agonist bromocriptine also augmented GHRH-stimulated GH secretion. Integrated GH secretion after a single iv injection of GHRH following two doses of bromocriptine was 160 +/- 29.5 ng/ml X h compared with 81.3 +/- 22.2 after placebo (P = 0.04). We suggest that these findings are compatible with the hypothesis that dopamine inhibits hypothalamic somatostatin secretion, which then allows for a greater stimulatory effect of GHRH.

Bromocriptine reduces growth hormone in acromegaly.

We assessed serum growth hormone (GH) levels in ten patients with acromegaly during a 24-hour profile and a 75-g oral glucose tolerance test (GTT). Serum GH levels were measured after five weeks of bromocriptine mesylate therapy, 20 mg daily (P1), after five weeks without bromocriptine mesylate therapy (P2), and again five weeks following restarting treatment with bromocriptine, 20 mg daily (P3). During the 24-hour profile, the following occurred: (1) mean serum GH level of the group was lower during P1 (20.5 mU/L) and P3 (20.8 mU/L) than P2 (49.6 mU/L); (2) in six individual patients during P1 and P3, there was a significant reduction in the mean serum GH value; and (3) a marked circadian variation in the serum GH value was present both with and without the drug therapy in five patients. During the GTT, the mean serum GH value was lower during P1 (18.4 mU/L) and P3 (16.7 mU/L) than P2 (43.3 mU/L), and in seven individual patients during P1 and P3, there was a significant reduction in the mean serum GH value. Overall, a clear reduction in serum GH values due to bromocriptine was demonstrated. In individual patients, serum GH values during a 24-hour profile and GTT gave similar indications of response.

Dopaminergic inhibition of growth hormone and prolactin release during continuous in vitro perifusion of normal and adenomatous human pituitary.

An in vitro technique for continuous perifusion of human pituitary has been developed to study the effect of dopamine on hormone release. Pituitary tissue was obtained from 2 patients with prolactinomas, 3 patients with acromegaly and 2 patients with disseminated malignancy whose pituitaries were normal. During perifusion prolactin release was reversibly inhibited from both normal and adenomatous glands, confirming the direct effect of dopamine on the pituitary. Rebound secretion following inhibition suggested that dopamine acted upon hormone release rather than synthesis under these conditions. Growth hormone (GH) release in vivo is stimulated by levodopa in normal subjects but inhibited in acromegaly. In vitro, however, we have demonstrated inhibition of GH release by dopamine, regardless of whether the pituitary was normal or adenomatous. This finding does not support the view that dopamine receptors are acquired by tumour cells as a result of adenomatous dedifferentiation. It is suggested that the paradoxical GH response to levodopa in acromegaly can be explained by a dual action of dopamine at hypothalamic and pituitary levels. According to this hypothesis GH release is stimulated by a hypothalamic effect, whereas inhibition occurs at pituitary level. The net effect of these opposing stimuli in vivo may depend upon the sensitivity of dopamine receptors at the prevailing concentration of GH.

 

[Jeffg353]

I need to do more research on this but could it be as simple as the negative feedback loop? Dopamine increases GHRH in hypothalamus which makes pituitary release GH. The body processes the Gh and liver converts to IGF-1 which tellss the hypothalamus to secret GHIH (somatostatin) and decreases GH secretion in pituitary.

 

[NFRCR]

The negative feedback loop always works. At the hypothalamus level the negative feedback loop results in inhibition of GHRH and release of Somastostatin. Dopamine will counteract this by inducing release of GHRH and inhibition of Somastostatin.

At the pituitary level Dopamine acts like Somastostatin by decreasing GH release in response to GHRH. However this only happens under certain conditions when the pituitary is sensitive to Dopamine. This kind of sensitivity is reported in acromegalic subjects whose GH is decreased when Dopamine agonists are given. Normal subjects see an increase equivalent to approximately 4IU HGH when given a low dose of a Dopamine agonist.

The reason I am researching this is that I've created an anomaly for myself in IGF-1 production, perhaps GH too. I mostly get quite low IGF-1 readings (110-180) and rarely higher 250-260.

I am 27. I have no history of GH deficiency. Age 19 IGF-1 390. Age 22 290.

I have taken Pramipexole for 4 years. I wanted to explore the effects and I somehow stayed on it (hard to get off due to withdrawal symptoms). And given that I have never seen this GH release described in literature, if anything I link it to suppression. I am taking a prolonged release version of it - serum levels stay stable for 24h. I am starting to suspect Dopamine-induced GH release needs to be pulsative, because in studies they used single dose immediate release version which has a half life of 8-12h - peak is at 2h and then fades away. Right now I am having constant dopaminergic stimulation, maybe this is bad.

I will do some experiments. First I'll take a large dose of Pramipexole and check GH/IGF-1 after 2h. Maybe only my IGF-1 synthesis has got messed up. Secondly I will drop Pramipexole for 2-3 days and test again.

I would really appreciate if anyone has IGF-1 levels to provide from times being on Pramipexole. I know not many have used it for GH release but Prolactin suppression. But IGF-1 is still a common value checked in mid-cycle bloods and Pramipexole is common for prolactin control.

 

[Jeffg353]

What kind of withdrawal symptoms do u experience when stopping? How "addictive" is prami? Some substances can cause seizures, tremors or even be deadly when u withdrawal from them, like alcohol or benzos...dont want u to end up hospitalized or anything. Good luck with ur experiments and stay safe

These articles I found are pretty crazy...

Loosening addiction's deadly grip

HealthUnlocked | The social network for health

 

[NFRCR]

Thanks for the support. I have not experienced any scary withdrawal symptoms as I have not gone without a dose for many days. As I do the experiment I will stay off it for a few days only and then take it again. If Pramipexole is the culprit for my low IGF-1 then I will taper the dose. I would not quit cold turkey but a few days off is tolerable.

Anyway, as I've intentionally skipped doses before I know how it will feel. Second day comes irritability, bad mood and bad dreams.

I might have also just found something to support my theory that GH release needs dopaminergic pulses instead of constant stimulation. Users have reported low IGF-1 while on Cabergoline - both with natural and exogenous GH so this is also seen in normal subjects and not only acromegalics. The half-life of caber is 63-69h so it can be considered a prolonger release drug.

The Prami I use has a short half-life but the prolonged release is achieved by making the pill break down very slowly.

Both are DA agonists. All DA agonists so far I've looked at increase GH except Caber. So it really must come down to how the dopaminergic effect is induced - pulses or constant.

 

[Old]

I would really appreciate if anyone has IGF-1 levels to provide from times being on Pramipexole. I know not many have used it for GH release but Prolactin suppression. But IGF-1 is still a common value checked in mid-cycle bloods and Pramipexole is common for prolactin control.

Haven't tried Pramipexole, but prescribed several DAs. IGF-1 was 141 on carbidopa/levodopa (8 years) + Amantadine (18 months) + Cabergoline (15 months). Don't have a base-line.
It's hard to know about cabergoline since studies discussing GH/IGF-1 are about either acromegaly or pituitary tumors. Perhaps something years ago for parkinsons but have only read that PD have higher GH than controls but it is too variable to be used as a marker.

 

[NFRCR]

Those prescriptions, are they one after another? And the IGF-1 reading is while on Cabergoline as I understand. You don't have them for Carbidopa/Levodopa and Amantadine separately. If not too personal question, how old are you and for what do you take these DA agonists?

Regarding Cabergoline, I found that it suppresses GH/IGF-1 in everyone. Other DA agonists increase GH in normal subjects and suppress it in acromegalics. However, the researches done on normal subjects always used a single dose and the goal was to find good substances for GH stimulation tests (high-dose arginine is also used for this purpose) rather than enhance GH output long-term. The GH output in these tests is so big that it exceeds the usual therapeutical doses of HGH so it's a bit unbelievable that this effect would not fade away or even be reversed with long-term use.

All the bodybuilding-community hype on Pramipexole increasing GH also references a study with a single dose.

 

[Old]

The reading was on all three, the times were how long had been on them. Mid 50's with Parkinsonism (but not IPD).

 

[NFRCR]

I have decided that first I will to the experiment of staying off Pramipexole for a few days rather than aim to correctly time the dosing. Regardless of timing I should not see low IGF-1 values because they're supposed to be relatively stable.

I have tens of blood test results and I was analyzing them like crazy to find correlations between various hormones and IGF-1. I found a few, but there were almost always exceptions that disproved strong correlations. Except for one correlation that was strong in all cases - it is between TSH and IGF-1. My TSH values while on Pramipexole have been between 1.3 and 2.3. The higher the TSH the higher the IGF-1 and vice-versa. Free-T4 has always been in range. Free-T3 is in the top part of the range or slightly over it (highest 6.7) which suggest that I have enhanced T4 to T3 conversion.

Now, I have pre-Pramipexole TSH levels. At age 19 it was 4.6 and age 22 it was 3.5. This clearly suggests that my TSH levels are suppressed in comparison to the baseline despite that my T4 and T3 are normal. I think this is the link that I've been looking for. Since I am now letting my TSH come back up there is a chance that T4 and T3 will go up as well so I will make sure to monitor those.

There are multiple pathways of how dopamine agonists inhibit GH release:

• Activation of dopamine D2-receptor at pituitary. This is counteracted if a D2-receptor antagonist is in place at the same time.
• Inhibiting TRH release which inhibits GH release (also inhibits TSH). One study found that TRH stimulatory effect on GH release might not be direct by through stimulating GHRH first.

It should be noted that dopamine inhibits GH release in acromegalics in only about half of the subjects and it seems to be dependent on thyroid status. I see no reason why this couldn't be the case with non-acromegalic subjects as well.

The various GH stimulation tests (L-Dopa, DA agonists) in non-agromegalics usually result in GH levels of 25-50 ng/mL. If this effect was long-term, which it most likely is not, anyone taking a DA agonist would become acromegalic. I find it very strange that only single dose tests have been done, seems very irresponsible from pharmaceutical companies even.

Furthermore, there could be a reason why some dopamine agonists, such as Cabergoline, are more likely to suppress GH release in normal subjects. It might or might not be the half-life, but more likely it is the D2-receptor binding affinity. Most DA agonists that activate the D2-receptor have higher binding affinity to it than dopamine itself. And Cabergoline has significantly higher affinity to D2-receptor than Pramipexole - Ki 0.62/0.95 compared to Ki 3.9/2.2 (lower value means higher affinity).

 

[Old]

With pituitary tumors, those that secret just prolactin and those that secret prolactin and GH respond best to cabergoline. Those that secret mainly GH respond better to bromocriptine. Yet the two are both strong D2 agonists. The metabolic pathway for D2 and prolactin is clear. But haven't seen any info regarding dopamine and GH. Curious to see how l-dopa stimulate GH (never looked before). It would seem to be transient for the reason you state. Then there is connection between dopamine and thyroid and between thyroid and GH.

 

[Sworder]

Dopamine increases, GH decreases. Simple

 

[NFRCR]

Dopamine increases, GH decreases. Simple

Not that simple.

In normal subjects dopamine will not initially strongly inhibit GH at pituitary, so their GH will increase. As dopamine (also agonist) levels build up, inhibition occurs.

 

[trackstar19]

Those prescriptions, are they one after another? And the IGF-1 reading is while on Cabergoline as I understand. You don't have them for Carbidopa/Levodopa and Amantadine separately. If not too personal question, how old are you and for what do you take these DA agonists?

Regarding Cabergoline, I found that it suppresses GH/IGF-1 in everyone. Other DA agonists increase GH in normal subjects and suppress it in acromegalics. However, the researches done on normal subjects always used a single dose and the goal was to find good substances for GH stimulation tests (high-dose arginine is also used for this purpose) rather than enhance GH output long-term. The GH output in these tests is so big that it exceeds the usual therapeutical doses of HGH so it's a bit unbelievable that this effect would not fade away or even be reversed with long-term use.

All the bodybuilding-community hype on Pramipexole increasing GH also references a study with a single dose.

I, too, have used prami for years (prior I was on caber but after seeing the Potential lowering of IGF-1 I promptly switched. I'm on 1mg a day. When I stopped in the past the withdrawals were hell.

Interestingly my IGF-1 level is low, too. 149 last time I checked :.. while on 5IU black tops, tren, 67.5mcg t3, 200mcg t4, insulin 2x a week, 200MG DNP, etc.

I suspected my low IGF-1 was from one of a few reasons:

-possible tanked estro levels (unsure on estro as the estrogen test performed was ECIA which messes up and reads wrong if on tren or other 19nor's)

- being on 67.5mcg t3 (I assumed the 200mcg of t4 would help but perhaps with my t3 dose it goes to waste and doesn't change over and cause the positive IGF-1 effects that occur with the T4 -> T3 connection

- perhaps DNP was inhibiting IGF-1 levels ... I don't know how but it is an awfully strong and disruptive drug.

- The black tops are impure GH that weren't folded properly so, despite showing up as GH when testing, it can't convert easily to IGF1.

I've been self diagnosing and trouble shooting to figure out which reason it is... I'm on the grey tops GH now and got blood drawn Friday for IGF-1 levels. If still low I'll add 100mg test a week to my stack (I haven't been running test)... then retest in a month ... if that is a no go I will drop the t3 and only be on the t4 and re-test a few weeks into that... if THAT doesn't do it I'll try all of that whilst ensuring I am off DNP, too.

Thoughts? My liver values are in range.

 

[NFRCR]

@trackstar19

As I understand you're currently on Pramipexole and exogenous GH while your IGF-1 levels are low.

I would rather think your GH is good and not bunk.

At least with Cabergoline GH/IGF-1 suppression is seen in case of endogenous GH and IGF-1 suppression is seen with exogenous GH. This means that it also impairs IGF-1 production. I do not know if Pramipexole is any different and suppresses only GH secretion or also IGF-1 production in response to GH. However, Cabergoline surely has a stronger suppressive effect.

Additionally, liver support drugs impair IGF-1 production. Are you taking any?

Other than that I can't think of a reason, T4/T3 should not be the issue. No idea about DNP though.

 

[trackstar19]

@trackstar19

As I understand you're currently on Pramipexole and exogenous GH while your IGF-1 levels are low.

I would rather think your GH is good and not bunk.

At least with Cabergoline GH/IGF-1 suppression is seen in case of endogenous GH and IGF-1 suppression is seen with exogenous GH. This means that it also impairs IGF-1 production. I do not know if Pramipexole is any different and suppresses only GH secretion or also IGF-1 production in response to GH. However, Cabergoline surely has a stronger suppressive effect.

Additionally, liver support drugs impair IGF-1 production. Are you taking any?

Other than that I can't think of a reason, T4/T3 should not be the issue. No idea about DNP though.

Ahh thank you for reminding me ... I completely forgot to mention I was on TUDCA during the previous test, and I am not this go around as I assumed that might be impacting the IGF-1 conversion in the liver. So that is the first variable I changed. I'll slowly go down the list of variables until I figure it out ... hoping it might just be the TUDCA.

DNP doesn't seem to negatively impact IGF-1 from my reading, but I'll change that variable when time if I haven't yet sorted it out

 

[NFRCR]

I unfortunately did not see a significant rise in IGF-1 after staying off Pramipexole for 72 hours.

Prolactin barely made it into the lower part of the reference range so perhaps the effect does not fade that fast.

However, free T4 went up a bit, still in range. T3 went up to 6.9 which is over the limit (6.5).

Also as I side note... HCT 51.1. Need to get rid of some blood soon.

I will now change Pramipexole dose from 1.04mg / day to 0.52mg / day followed by 0.52mg / day. If then IGF-1 rises I will switch to immediate release pills instead of extended release. If not... I'll stay on lower dose of Prami or get off it completely.

@trackstar19 looking forward to your results while being off TUDCA. It will be interesting.

 

[NFRCR]

I managed to find some pre-steroid-use blood test results. I have two years of blood test results where my IGF-1 ranges from 200 to 250 (considerably higher than now) while being on Pramipexole. I still do have a reason to believe that Pramipexole lowers IGF-1 because that is lower than my baseline at age 22 which was 290.

But another contributing factor to the IGF-1 decrease seems to be long Trenbolone runs. The times when my IGF-1 has started climbing up again have been when I get off Tren.

Regarding Pramipexole, it theoretically can be used to enhance IGF-1 levels long-term, but then the immediate-release version must be used. And even the immediate release version must be dosed at long-enough intervals to create a big enough amplitude between low and high dopamine agonist levels to stimulate GH secretion.

However, the immediate-release version is supposed to be dosed 2-3 a day to maintain stable serum levels (and this constant high level will counteract GH secretion). Otherwize the levels will fluctuate which is not healthy. The only exception here is very low dose Pramipexole once a day for RLS (restless legs syndrome) - the dose is small enough to not create big fluctuations and not shut down natural dopamine production. To sum it up, moderate-high (0.5mg and up) dose of Pramipexole once a day - not recommended.

 

[trackstar19]

I managed to find some pre-steroid-use blood test results. I have two years of blood test results where my IGF-1 ranges from 200 to 250 (considerably higher than now) while being on Pramipexole. I still do have a reason to believe that Pramipexole lowers IGF-1 because that is lower than my baseline at age 22 which was 290.

But another contributing factor to the IGF-1 decrease seems to be long Trenbolone runs. The times when my IGF-1 has started climbing up again have been when I get off Tren.

Regarding Pramipexole, it theoretically can be used to enhance IGF-1 levels long-term, but then the immediate-release version must be used. And even the immediate release version must be dosed at long-enough intervals to create a big enough amplitude between low and high dopamine agonist levels to stimulate GH secretion.

However, the immediate-release version is supposed to be dosed 2-3 a day to maintain stable serum levels (and this constant high level will counteract GH secretion). Otherwize the levels will fluctuate which is not healthy. The only exception here is very low dose Pramipexole once a day for RLS (restless legs syndrome) - the dose is small enough to not create big fluctuations and not shut down natural dopamine production. To sum it up, moderate-high (0.5mg and up) dose of Pramipexole once a day - not recommended.

Ready to be confused?

.... in December i had an IGF-1 reading of 149 like stated ... which was very disappointing ... this time around ..... 77. My IGF-1 is essentially non-existent. Liver values aren't bad, my GH is good. One of the many combos of drugs I am on is clearly inhibiting the process of conversion. I'm going to continue to use GH even though I'm not
Getting IGF-1 conversion ... but I think I might, too, add in IGF-1 LR3. I might have a source for incrilex and fuck it I'll just pay the money and see if that helps

 

[NFRCR]

Ready to be confused?

.... in December i had an IGF-1 reading of 149 like stated ... which was very disappointing ... this time around ..... 77. My IGF-1 is essentially non-existent. Liver values aren't bad, my GH is good. One of the many combos of drugs I am on is clearly inhibiting the process of conversion. I'm going to continue to use GH even though I'm not
Getting IGF-1 conversion ... but I think I might, too, add in IGF-1 LR3. I might have a source for incrilex and fuck it I'll just pay the money and see if that helps

How old are you? Not sure if you've mentioned earlier.

Why don't you try to find the drug that is causing this? What was the list of them again and what do you yourself suspect the most? Surely it is not worth taking it. Did you test for serum GH too?

 

[trackstar19]

How old are you? Not sure if you've mentioned earlier.

Why don't you try to find the drug that is causing this? What was the list of them again and what do you yourself suspect the most? Surely it is not worth taking it. Did you test for serum GH too?

I trust the GH both times - both frequently tested everywhere and from TP (his black tops and the grey tops). I am going to figure it out via process of elimination. I thought it might have been the TUDCA since studies have stated it can impair IGF-1 conversion in the liver ... so that was the first variable I removed. Clearly a healthy liver thanks to TUDCA was worth more IGF-1 wise than removing it.

My next hypothesis is low estrogen. I need the sensitive non ECIA estro test so it will be accurate. I'll get it into normal range and wait a few months and re-test. If that fails I will remove DNP and see if that is the culprit. From there I'm a bit unsure - possibly remove the t3 and up the t4 and re-test. It'll take awhile but I would like to pinpoint it and correct it. I'm in this for the long haul so I'm okay with doing it this way.

My cycles stay similar - I cruise in between but currently:
Tren e
Anavar
Proviron
67.5mcg t3
200mcg t4
200mg DNP
5IU ED grey tops GH
30IU novolin R 3x a week
100mcg clen off and on
1mg prami ED

Currently in prep mode. Considering spending the money and buying real IGF-1 to make up for my deficiency while I attempt to fix it.