GH any positive uses?

Thanks for posting this. Just out of interest, by what mechanism does GH cause fluid retention?

Very nice

Good post JB, can't wait to use it some years from now.

Posted by: HitMeBack

Thanks for posting this. Just out of interest, by what mechanism does GH cause fluid retention?

I'm not JB, but I guess you may find your answer here: https://www.growxxl.com/peptides/gh-effects-on-muscle

I find this interesting. I have heard from more than 1 person that has have used GH in the past that it was a waste of time an money. I am sure it has its place for some but after careful consideration I think I will hold off...................for now

Posted by: guijr

I'm not JB, but I guess you may find your answer here: https://www.growxxl.com/peptides/gh-effects-on-muscle

Nope, the answer isn't there. Testosterone causes fluid retention due to aromatization. How does GH cause fluid retention?
Surely someone here knows!

Sodium retention.

Posted by: HitMeBack

Thanks for posting this. Just out of interest, by what mechanism does GH cause fluid retention?

jb

===================

J Clin Endocrinol Metab. 1996 Mar;81(3):1123-8. Links
Short-term growth hormone (GH) treatment of GH-deficient adults increases body sodium and extracellular water, but not blood pressure.Hoffman DM, Crampton L, Sernia C, Nguyen TV, Ho KK.
Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia.

Initiation of GH treatment in adults is frequently complicated by the development of symptomatic fluid retention. To investigate the mechanism and extent of fluid retention that occurs with dosages of GH used in the treatment of GH-deficient adults, we conducted a double blind study in which seven GH-deficient patients (aged 24-74 yr) each received in random order daily sc injections of placebo, a physiological dose of GH (0.04 U/kg, low dose), and a supraphysiological dose of GH (0.08 U/kg, high dose) for 7 days, separated by 21-day washout periods. On the seventh day, measurements were made of serum insulin-like growth factor I, body weight, exchangeable sodium, plasma volume, angiotensinogen, PRA, aldosterone, atrial natriuretic peptide (ANP), and mean 24-h ambulatory heart rate and blood pressure. GH significantly increased mean insulin-like growth factor I levels from 105 +/- 11 to 304 +/- 45 micrograms/L during low dose treatment (P = 0.006) and 400 +/- 76 micrograms/L during high dose treatment (P = 0.004). High dose GH caused a 1.2 +/- 0.3 kg increase in body weight (P = 0.01) and a 193 +/- 65 mmol increase in exchangeable sodium (P = 0.008). Low dose GH had a lesser effect, with no significant increase in body weight, but an increase in exchangeable sodium of 113 +/- 37 mmol (P = 0.02). Plasma volume was not significantly affected by GH treatment. Mean supine angiotensinogen levels were significantly higher during both GH treatments compared to placebo (low dose, P = 0.017; high dose, P = 0.028) as were mean supine PRA levels (low dose, P = 0.0002; high dose, P = 0.0025). Supine angiotensin II, aldosterone, and ANP levels were not significantly affected by GH treatment. There was no significant change from placebo in any of the sodium-regulating hormones in the erect posture. The mean 24-h heart rate was significantly higher during low dose (82 +/- 2 beats/min; P = 0.0001) and high dose (88 +/- 3 beats/min; P = 0.0001) GH treatment than during placebo (67 +/- 3 beats/min). However, no significant change in mean 24-h systolic or diastolic blood pressure was observed. In summary, acute GH administration using doses currently employed in treating adults causes a dose-related increase in body weight and body sodium, but no associated increase in blood pressure. We conclude that 1) sodium retention is a physiological effect of GH, but does not cause an acute rise in blood pressure; and 2) the mechanism of sodium and fluid retention is not primarily due to enhanced aldosterone secretion or inhibition of ANP release, but more likely to a direct renal tubular effect.

Posted by: HitMeBack

Thanks for posting this. Just out of interest, by what mechanism does GH cause fluid retention?

J Clin Endocrinol Metab. 2002 Apr;87(4):1743-9.

GH increases extracellular volume by stimulating sodium reabsorption in the distal nephron and preventing pressure natriuresis.

Johannsson G, Sverrisdottir YB, Ellegard L, Lundberg PA, Herlitz H.

Research Center for Endocrinology and Metabolism, Department of Clinical Neurophysiology, Sahlgrenska University Hospital, Goteborg SE-413 45, Sweden.

Although sodium retention and volume expansion occur during GH administration, blood pressure is decreased or unchanged. The aim was to study the effect of short- and long-term GH replacement in adults on sodium balance, renal hemodynamics, and blood pressure. Ten adults with severe GH deficiency were included into a 7-d, randomized, placebo-controlled, cross-over trial followed by 12 months of open GH replacement. All measurements were performed under metabolic ward conditions. Extracellular water (ECW) was determined using multifrequency bioelectrical impedance analysis. Renal plasma flow and glomerular filtration rate were assessed using renal paraminohippurate and Cr(51) EDTA clearances, respectively. Renal tubular sodium reabsorption was assessed using lithium clearance. Plasma renin activity (PRA), plasma concentrations of angiotensin II, aldosterone, atrial natriuretic peptides and brain natriuretic peptides (BNP) and 24-h urinary norepinephrine excretion were measured. Seven days of GH treatment decreased urinary sodium excretion. Lithium clearance as a marker of proximal renal tubular sodium reabsorption was unaffected by GH treatment. ECW was increased after both short- and long-term treatment. This increase was inversely correlated to the decrease in diastolic blood pressure (r = -0.70, P = 0.02) between baseline and 12 months. Short-term treatment increased PRA and decreased BNP. The increase in PRA correlated with an increase in 24-h urinary norepinephrine excretion (r = 0.77, P < 0.01). Glomerular filtration rate and renal plasma flow did not change during treatment. The sodium- and water-retaining effect of GH takes place in the distal nephron. The sustained increase in ECW in response to GH is associated with an unchanged or decreased blood pressure. This together with unchanged or decreased atrial natriuretic peptides and BNP may prevent pressure-induced escape of sodium.

--------------------------------------------------

J Clin Endocrinol Metab. 2005 Jul;90(7):3989-94.

Independent and combined effects of testosterone and growth hormone on extracellular water in hypopituitary men.

Johannsson G, Gibney J, Wolthers T, Leung KC, Ho KK.

Pituitary Research Unit, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia.

CONTEXT: Symptoms of fluid retention in GH-deficient patients during GH replacement are greater in men than in women, suggesting that testosterone may augment or estradiol may attenuate the antinatriuretic actions of GH. The mechanisms underlying the sodium-retaining effects of GH are poorly understood. AIM: The aim of this study was to investigate the effects of GH and testosterone, alone and in combination, on extracellular water (ECW) and the hormonal mechanisms involved. DESIGN: Two separate, open-label, randomized, two-period, crossover studies were performed; the first compared the effects of GH alone with those of GH and testosterone, and the second compared the effects of testosterone alone with those of GH and testosterone. PARTICIPANTS: Twelve hypopituitary men with GH deficiency and hypogonadism were studied. INTERVENTION: During the weeks of intervention, GH (0.5 mg/d) and Testosterone Enanthate (250 mg) were administered by im injection. OUTCOME MEASURES: The outcome measures were ECW, IGF-I, plasma renin activity (PRA), aldosterone (Aldo), and atrial natriuretic peptide (ANP). RESULTS: GH treatment significantly increased (P < 0.05) both IGF-I and ECW, and these changes were enhanced by cotreatment with testosterone (P = 0.07 for both). PRA, Aldo, and ANP levels did not change. Testosterone treatment alone did not change the IGF-I concentration, whereas cotreatment with GH induced a marked increase. Testosterone alone increased (P < 0.05) ECW, and the effect was augmented (P < 0.01) by cotreatment with GH. Although PRA and ANP did not change, plasma Aldo decreased after single and combined treatments. CONCLUSION: GH and testosterone exerted independent and additive effects on ECW. The mechanisms of fluid retention for both hormones are likely to be exerted on the renal tubules. This is the first direct evidence that testosterone increases ECW.

maybe by renin and atrial natriretic peptide

Clin Endocrinol (Oxf). 2000 Feb;52(2):181-6.

Insulin-like growth factor I administration induces fluid and sodium retention in healthy adults: possible involvement of renin and atrial natriuretic factor.

Moller J, Jorgensen JO, Marqversen J, Frandsen E, Christiansen JS.

Medical Department, Silkeborg Centralsygehus, Silkeborg; University Department of Endocrinology and Diabetes, Aarhus Kommunehospital, Aarhus, Denmark.

OBJECTIVE: Growth hormone induces fluid and sodium retention. The underlying mechanism is, however, incompletely understood. A possible mediator could be IGF-I. To investigate the impact of IGF-I administration on body fluid distribution and sodium homeostasis in healthy subjects, we examined normal subjects during six days IGF-I treatment and during a six-day control period. DESIGN AND MEASUREMENTS: Eight normal male subjects aged 23-30 years were randomised to receive IGF-I 50 microg/kg subcutaneously thrice daily during a six day study period, and to a six day control period. After each study period, extracellular volume and plasma volume (ECV, PV) were determined using 82Br and 125I-albumin. Blood samples, urinary sodium excretion, and bioimpedance were measured every second day of each study period. RESULTS: Serum IGF-I (microg/l) increased during active treatment (control, 293 +/- 9; IGF-I, 628 +/- 42; P < 0.01). ECV (l) was expanded by IGF-I (control, 18.42 +/- 0.28; IGF-I, 19.72 +/- 0.50; P < 0.05) whereas PV (l) remained unaffected (control, 3.76 +/- 0.11; IGF-I, 3.80 +/- 0.16; n.s.). Likewise, bioimpedance and body weight were unchanged by IGF-I. Plasma renin (mU/l) increased but not significantly during IGF-I (control, 28.7 +/- 2.7; IGF-I, 39.9 +/- 4.3; P = 0.08), and plasma aldosterone was unaffected by IGF-I. N-Terminal proANF (pmol/l) was suppressed during IGF-I administration (control, 422 +/- 32; IGF-I, 330 +/- 20; P < 0.05). Diurnal sodium excretion (mmol) was reduced during IGF-I administration (control, 151 +/- 8; IGF-I, 124 +/- 7; P < 0.05). CONCLUSION: IGF-I treatment causes fluid and sodium retention. This may be mediated by increased renin release and suppression of atrial natriuretic factor. ]The present data suggest that the fluid and sodium retaining effect of GH is at least partly mediated through IGF-I.

-------------------------------

J Clin Endocrinol Metab. 2002 Apr;87(4):1743-9.

GH increases extracellular volume by stimulating sodium reabsorption in the distal nephron and preventing pressure natriuresis.

Johannsson G, Sverrisdottir YB, Ellegard L, Lundberg PA, Herlitz H.

Research Center for Endocrinology and Metabolism, Department of Clinical Neurophysiology, Sahlgrenska University Hospital, Goteborg SE-413 45, Sweden.

Although sodium retention and volume expansion occur during GH administration, blood pressure is decreased or unchanged. The aim was to study the effect of short- and long-term GH replacement in adults on sodium balance, renal hemodynamics, and blood pressure. Ten adults with severe GH deficiency were included into a 7-d, randomized, placebo-controlled, cross-over trial followed by 12 months of open GH replacement. All measurements were performed under metabolic ward conditions. Extracellular water (ECW) was determined using multifrequency bioelectrical impedance analysis. Renal plasma flow and glomerular filtration rate were assessed using renal paraminohippurate and Cr(51) EDTA clearances, respectively. Renal tubular sodium reabsorption was assessed using lithium clearance. Plasma renin activity (PRA), plasma concentrations of angiotensin II, aldosterone, atrial natriuretic peptides and brain natriuretic peptides (BNP) and 24-h urinary norepinephrine excretion were measured. Seven days of GH treatment decreased urinary sodium excretion. Lithium clearance as a marker of proximal renal tubular sodium reabsorption was unaffected by GH treatment. ECW was increased after both short- and long-term treatment. This increase was inversely correlated to the decrease in diastolic blood pressure (r = -0.70, P = 0.02) between baseline and 12 months. Short-term treatment increased PRA and decreased BNP. The increase in PRA correlated with an increase in 24-h urinary norepinephrine excretion (r = 0.77, P < 0.01). Glomerular filtration rate and renal plasma flow did not change during treatment. The sodium- and water-retaining effect of GH takes place in the distal nephron. The sustained increase in ECW in response to GH is associated with an unchanged or decreased blood pressure. This together with unchanged or decreased atrial natriuretic peptides and BNP may prevent pressure-induced escape of sodium.

---------------------------------

J Clin Endocrinol Metab. 1991 Apr;72(4):768-72.

Expansion of extracellular volume and suppression of atrial natriuretic peptide after growth hormone administration in normal man.

Moller J, Jorgensen JO, Moller N, Hansen KW, Pedersen EB, Christiansen JS.

University Department of Endocrinology and Internal Medicine, Aarhus Kommunehospital, Denmark.

Sodium retention and symptoms and signs of fluid retention are commonly recorded during GH administration in both GH-deficient patients and normal subjects. Most reports have however, been casuistic or uncontrolled. In a randomized double blind placebo-controlled cross-over study we therefore examined the effect of 14-day GH administration (12 IU sc at 2000 h) on plasma volume, extracellular volume (ECV), atrial natriuretic peptide (ANP), arginine vasopressin, and the renin angiotensin system in eight healthy adult men. A significant GH induced increase in serum insulin growth factor I was observed. GH caused a significant increase in ECV (L): 20.45 +/- 0.45 (GH), 19.53 +/- 0.48 (placebo) (P less than 0.01), whereas plasma volume (L) remained unchanged 3.92 +/- 0.16 (GH), 4.02 +/- 0.13 (placebo). A significant decrease in plasma ANP (pmol/L) after GH administration was observed: 2.28 +/- 0.54 (GH), 3.16 +/- 0.53 (placebo) P less than 0.01. Plasma aldosterone (pmol/L): 129 +/- 14 (GH), 89 +/- 17 (placebo), P = 0.08, and plasma angiotensin II (pmol/L) levels: 18 +/- 12 (GH), 14 +/- 7 (placebo), P = 0.21, were not significantly elevated. No changes in plasma arginine vasopressin occurred (1.86 +/- 0.05 pmol/L vs. 1.90 +/- 0.05, P = 0.33). Serum sodium and blood pressure remained unaffected. Moderate complaints, which could be ascribed to water retention, were recorded in four subjects [periorbital edema (n = 3), acral paraesthesia (n = 2) and light articular pain (n = 1)]. The symptoms were most pronounced after 2-3 days of treatment and diminished at the end of the period. In summary, 14 days of high dose GH administration caused a significant increase in ECV and a significant suppression of ANP.

--------------------------

or a direct effect of GH or of IGF-I on renal tubular function

Posted by: HitMeBack

Nope, the answer isn't there. Testosterone causes fluid retention due to aromatization. How does GH cause fluid retention?
Surely someone here knows!

respect testosterone:

Vasopressin (Anti diuretic hormone, ADH) release:

J Neuroendocrinol. 2001 May;13(5):442-52.

Androgens alter corticotropin releasing hormone and arginine vasopressin mRNA within forebrain sites known to regulate activity in the hypothalamic-pituitary-adrenal axis.

Viau V, Soriano L, Dallman MF.

Department of Physiology, University of California, San Francisco 94143-0444, USA.

To reveal direct effects of androgens, independent of glucocorticoids, we studied the effects of gonadectomy (GDX) in adrenalectomized (ADX) rats with or without androgen replacement on corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) mRNA expression within various forebrain sites known to regulate the hypothalamic-pituitary-adrenal axis. These included the medial parvocellular portion of the paraventricular nucleus of the hypothalamus (mp PVN), the central and medial nuclei of the amygdala and bed nuclei of the stria terminalis (BNST). In the mp PVN, ADX stimulated both CRH and AVP mRNA expression. Combined ADX + GDX inhibited only AVP, and testosterone and dihydrotestosterone (DHT) restored AVP mRNA. In the central nucleus of the amygdala, ADX decreased CRH mRNA expression, and this response was unaffected by GDX +/- testosterone or DHT replacement. In the medial amygdala, AVP mRNA expression was decreased by ADX, abolished by ADX + GDX, and restored by androgen replacement. ADX had no effect on CRH and AVP mRNA expression in the BNST. GDX + ADX, however, reduced CRH mRNA expression only within the fusiform nuclei of the BNST and reduced the number of AVP-expressing neurones in the posterior BNST. Androgen replacement reversed both responses. In summary, in ADX rats, AVP, but not CRH mRNA expression in the amygdala and mp PVN, is sensitive to GDX +/- androgen replacement. Both CRH- and AVP-expressing neurones in the BNST respond to GDX and androgen replacement, but not to ADX alone. Because androgen receptors are not expressed by hypophysiotropic PVN neurones, we conclude that glucocorticoid-independent, androgenic influences on medial parvocellular AVP mRNA expression are mediated upstream from the PVN, and may involve AVP-related pathways in the medial amygdala, relayed to and through CRH- and AVP-expressing neurones of the BNST.

-----------------------------------

J Clin Endocrinol Metab. 2002 Jan;87(1):136-43.

The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men.

Singh AB, Hsia S, Alaupovic P, Sinha-Hikim I, Woodhouse L, Buchanan TA, Shen R, Bross R, Berman N, Bhasin S.

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059, USA.

The effects of T supplementation on insulin sensitivity, inflammation-sensitive markers, and apolipoproteins remain poorly understood. We do not know whether T's effects on plasma lipids, apolipoproteins, and insulin sensitivity are dose dependent, or whether significant anabolic effects can be achieved at T doses that do not adversely affect these cardiovascular risk factors. To determine the effects of different doses of T, 61 eugonadal men, 18-35 yr of age, were randomly assigned to 1 of 5 groups to receive monthly injections of long-acting GnRH agonist to suppress endogenous T secretion and weekly injections of 25, 50, 125, 300, or 600 mg T enanthate for 20 wk. Dietary energy and protein intakes were standardized. Combined administration of GnRH agonist and graded doses of T enanthate resulted in nadir T concentrations of 253, 306, 542, 1345, and 2370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Plasma high density lipoprotein cholesterol and apolipoprotein A-I concentrations were inversely correlated with total and free T concentrations and were significantly decreased only in the 600 mg/wk group (change in high density lipoprotein cholesterol: -8 +/- 2 mg/dl; P = 0.0005; change in apolipoprotein A-I: -16 +/- 2 mg/dl; P = 0.0001). Serum total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, triglycerides, apolipoprotein B, and apolipoprotein C-III were not significantly correlated with T dose or concentration. There was no significant change in total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, triglycerides, apolipoprotein B, or apolipoprotein C-III levels at any dose. The insulin sensitivity index, glucose effectiveness, and acute insulin response to glucose, derived from the insulin-modified, frequently sampled, iv glucose tolerance test using the Bergman minimal model, did not change significantly at any dose. Circulating levels of C-reactive protein were not correlated with T concentrations and did not change with treatment in any group. Significant increments in fat-free mass, muscle size, and strength were observed at doses that did not affect cardiovascular risk factors. Over a wide range of doses, including those associated with significant gains in fat-free mass and muscle size, T had no adverse effect on insulin sensitivity, plasma lipids, apolipoproteins, or C-reactive protein. Only the highest dose of T (600 mg/wk) was associated with a reduction in plasma high density lipoprotein cholesterol and apolipoprotein A-I. Long-term studies are needed to determine whether T supplementation of older men with low T levels affects atherosclerosis progression.
Total and free T, and E2 concentrations

Serum total and free T levels have been previously reported (16). Mean (�SEM) serum total T concentrations in the five groups, 7 d after previous T injection, were 253 � 66, 306 � 58, 570 � 75, 1345 � 139, and 2370 � 150 ng/dl, respectively; the corresponding free T concentrations were 29 � 5, 32 � 3, 52 � 8, 138 � 21, and 275 � 30 pg/ml, respectively. Serum E2 concentrations were not significantly different in the five treatment groups at baseline (21.6 � 2.3, 21.3 � 3.5, 20.3 � 3.1, 27.1 � 1.8, and 19.5 � 1.6 pg/ml; P = NS), but increased significantly during treatment only in men receiving 300 and 600 mg T enanthate weekly (wk 20 values, 15.2 � 1.8, 14.2 � 1.1, 22.8 � 3.0, 43.0 � 5.3, and 55.7 � 5.3; P = 0.0012) * Serum E2 concentrations were highly correlated with serum total T concentrations (r = 0.76; P = 0.0001). Serum total T, free T, and E2 levels measured during the last treatment week after the previous injection were linearly dependent on the T dose (P = 0.0001). In men receiving the 25- and 50-mg doses, nadir total and free T concentrations decreased from baseline and were at or below the lower limit of the normal range for healthy young men. In contrast, serum total and free T concentrations increased significantly from baseline and were in the supraphysiological range in men receiving the 300- and 600-mg doses.

* +/- normal values for estrogen
10-50 pg/ml.

http://jcem.endojournals.org/cgi/content/full/87/1/13 6" target="_blank" rel="noopener"> http://jcem.endojournals.org/cgi/content/full/87/1/136

--------------------------------

Am J Kidney Dis. 2006 May;47(5):727-37.

Vasopressin excess and hyponatremia.

Pham PC.

Nephrology Division, Olive View-UCLA Medical Center, Sylmar, CA 91342, USA.

Hyponatremia is a common electrolyte disorder that frequently is overlooked and undertreated. Although the pathophysiological process of hyponatremia is complex, arginine vasopressin (AVP) is a common etiologic factor. Excess AVP release by osmotic or nonosmotic stimuli or both can lead to sodium and water imbalance. Conventional treatment options for hyponatremia, including water restriction and administration of sodium chloride with or without loop diuretics, do not directly address the underlying water retention induced by excess AVP in many cases. Clinical trials showed that AVP-receptor antagonists, including lixivaptan, tolvaptan, and conivaptan, produce aquaresis, the electrolyte-sparing excretion of free water, to correct serum sodium concentration. We review results from recent clinical trials involving AVP-receptor antagonists in the treatment of hyponatremia associated with AVP excess.

hgh fluid retention

or

Growth Horm IGF Res. 2000 Aug;10(4):187-92.

Differences in the effects of 20 K- and 22 K-hGH on water retention in rats.

Satozawa N, Takezawa K, Miwa T, Takahashi S, Hayakawa M, Ooka H.

Medicinal Research Department, Institute of Biological Science, Mitsui Pharmaceuticals Inc., Chiba, Japan.

Antidiuretic actions induced by two growth hormone (GH) isoforms (20 K- and 22 K-hGH; 0.2 and 2.0 mg/kg) were evaluated in rats, as fluid retention may cause oedema, one of the adverse effects of GH. Both GH isoforms (2.0 mg/kg) suppressed urine excretion in hypophysectomized rats (P< 0.01), but only the 22 K-hGH isoform (2.0 mg/kg) suppressed urine excretion in intact rats (P< 0.01). In addition, prolactin (PRL) suppressed urine excretion in intact rats (P< 0.05). In conclusion, 20 K-hGH has less potency in causing urine retention than 22 K-hGH and since 20 K-hGH is missing 15 amino acids found in 22 K-hGH, these amino acids may be important for the antidiuretic action of GH. Since prolactin suppressed urine excretion, a part of the antidiuretic action of GH may be related to PRL-R activation

Mol Endocrinol. 2006 Mar;20(3):661-74.

Two wrongs can make a right: dimers of prolactin and growth hormone receptor antagonists behave as agonists.

Langenheim JF, Tan D, Walker AM, Chen WY.

Department of Biological Sciences, Clemson University, Clemson, SC 29634-0326, USA.

Prolactin (PRL) and GH have two distinct binding sites (site 1 with high affinity; site 2 with low affinity) that each interact with a PRL receptor (PRLR) to form a functional receptor dimer that activates signal transduction. The G129R mutation in PRL and the G120R mutation in GH disrupt the structural integrity of site 2 such that the ligands retain the ability to bind to the first receptor with high affinity, but act as receptor antagonists. In this study, we examined the ability of monomeric and dimeric forms of these ligands, human (h) PRL and hGH, and their antagonists (hPRL-G129R and hGH-G120R) to 1) bind to PRLRs; 2) induce conformational changes in PRLRs; 3) activate signaling pathways associated with the PRLR; and 4) mediate cell proliferation in vitro. In contrast to monomeric hPRL-G129R, homodimeric hPRL-G129R induced PRLR dimerization; activated Janus family of tyrosine kinases 2/signal transducer and activator of transcription 5, Ras/Raf/MAPK kinase/Erk, and phosphatidylinositol 3-kinase/Akt signaling; and stimulated Nb2 cell proliferation. Similarly, homodimeric hGH-G120R was able to mediate signaling via the PRLR and to stimulate Nb2 cell proliferation. These experiments demonstrate that a ligand must have two functional binding sites, but that these may be site 1 plus site 2 or two site 1's, to elicit receptor-mediated signal transduction. The size of the ligand plays less of a role in receptor activation, suggesting that the extracellular portion of the PRLR (and possibly the GH receptor) is rather flexible and can accommodate larger ligands. These findings may have implications for designing multifunctional therapeutics that target this class of cytokine receptors.

So Spironolactone would be the solution to the water retention problem?

Thanx for posting the above studies!

Posted by: HitMeBack

Thanx for posting the above studies!

at your service.

Posted by: Seabiscuit Hogg

So Spironolactone would be the solution to the water retention problem?

no way cos,
from the studies:

"Although PRA and ANP did not change, plasma Aldo decreased after single and combined treatments"

-----------------------------

"and plasma aldosterone was unaffected by IGF-I".

------------------------------------------

"Plasma aldosterone (pmol/L): 129 +/- 14 (GH), 89 +/- 17 (placebo), P = 0.08, and plasma angiotensin II (pmol/L) levels: 18 +/- 12 (GH), 14 +/- 7 (placebo), P = 0.21, were not significantly elevated"

------------------------------------
from the study posted by JB

"the mechanism of sodium and fluid retention is not primarily due to enhanced aldosterone secretion or inhibition of ANP release, but more likely to a direct renal tubular effect."

now, i am thinking more about :

from

J Clin Endocrinol Metab. 2005 Jul;90(7):3989-94.

Independent and combined effects of testosterone and growth hormone on extracellular water in hypopituitary men.

Johannsson G, Gibney J, Wolthers T, Leung KC, Ho KK.

Pituitary Research Unit, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia.

"......................GH and testosterone exerted independent and additive effects on ECW. The mechanisms of fluid retention for both hormones are likely to be exerted on the renal tubules....................".

from

Mol Interv. 2005 Dec;5(6):338-40.

Few things in life are "free": cellular uptake of steroid hormones by an active transport mechanism.

Lin BC, Scanlan TS.

Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-2280, USA.

Conventional dogma holds that steroid hormones traverse cell membranes passively, owing to their lipophilic nature. The recently characterized protein megalin, however, functions as a transport protein on cell surfaces to carry steroids across the plasma membrane. Upon hydrolysis of steroid-associated binding globulins in lysosomes, free hormone is liberated and may exert its effects in the cell. Megalin-independent mechanisms of steroid uptake are likely important too, as the phenotypes of megalin-deficient mice do not completely mimic the phenotypes of androgen receptor� or estrogen receptor�null mice.

Steroid hormones participate in the regulation of normal vertebrate homeostasis, development, and reproduction. The best understood mechanism of steroid action is for these signaling molecules to enter target cells and bind to their cognate intracellular receptors that, subsequently, regulate the transcription of corresponding steroid responsive genes. Defects in these signaling pathways can lead to a variety of endocrine and neoplastic disorders.

Recent findings refute the long-held notion that lipophilic hormones, such as androgens and estrogens, solely diffuse into cells by a free, non-specific mechanism. Megalin (2, 3), a member of the low density lipoprotein receptor superfamily of endocytic proteins, has been identified as an important facilitator of steroid entry into cells. Previous work by Nykjaer and colleagues (4) has demonstrated the existence of megalin-dependent endocytic pathways for tissue specific uptake of complexed vitamin D [i.e., 25-(OH) vitamin D3 bound to vitamin D binding protein (DBP)], suggesting that megalin may be important in maintaining steroid hormone balance in mammals. Specifically, they demonstrated that megalin knockout (KO) mice were unable to resorb the vitamin into the epithelial cells of the renal proximal tubules, where the receptor is normally expressed these megalin-null animals developed bone calcification defects.......

.......In addition to the renal proximal tubules, megalin is expressed in a variety of other tissues, including ones that are steroid responsive