Neuroendocrine alterations in the somatotropic and lactotropic axes in uremic men

Abstract

To investigate the pathophysiology of altered growth hormone (GH) and prolactin secretion in endstage renal disease, we sampled blood at 10-min intervals for 24 h and applied deconvolution analysis to calculate hormone half-lives and pulsatile secretion rates. Two-site immunoradiometric assays were employed to quantitate presumptively intact GH and prolactin in nine middle-aged men with chronic renal failure and 14 gender-, age-, body weight- and community-matched controls. We observed that the half-lives of endogenous GH and prolactin were prolonged significantly in uremia: for GH, control 17 +/- 1.4 versus uremia 21 +/- 1.3 min (p < 0.05); for prolactin, control 66 +/- 9.3 versus uremia 112 +/- 10 min (p < 0.01). Daily GH secretion rates exceeded sex-, age- and weight-predicted values in eight of nine uremic individuals, while values for prolactin were variable but on average twofold higher in uremia. In both the somatotropic and lactotropic axes, the frequency of secretory bursts was increased significantly (for GH, control 11 +/- 1.1 versus uremia 15 +/- 0.84 secretory events/24 h: for prolactin, control 20 +/- 0.90 versus uremia 27 +/- 1.3 pulses/24 h, p < 0.05). Although there were no significant alterations in the mean amplitude, duration or mass of GH secretory bursts, prolactin secretory burst amplitudes were elevated threefold in uremia (p < 0.01). These distinctive mechanisms brought about higher 24-h mean serum concentrations of GH (0.70 +/- 0.17 control versus 1.22 +/- 0.32 micrograms/l uremia) and prolactin (7.3 +/- 2.4 control versus 26 +/- 6.1 micrograms/l uremia, p < 0.05). Lastly, serum concentrations of estradiol were increased but those of unconjugated estriol decreased in uremia. We conclude that hypersomatotropinemia and hyperprolactinemia in uremic men result from prolonged hormone half-lives combined with increased frequencies of secretory events driven by unknown stimuli within the respective axes, and/or by defects in their negative-feedback regulation. We postulate that the latter may arise from partial tissue resistance to hormone action in hemodialyzed men.

Prevalence of subnormal testosterone concentrations in men with type 2 diabetes and chronic kidney disease

“…Decreased clearance and increased production are responsible for the elevation of prolactin in CKD (26). Consistent with other studies, we found higher prolactin concentrations in patients with CKD (17).…”

Elevated Levels of Serum Prolactin in Patients with Advanced Multiple Myeloma

“…Hyperprolactinemia was reported in patients with renal insufficiency [31]. We have not noticed any significant differences between the serum PRL level of stage III patients with (III/B) and without (III/A) renal impairment.…”

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

“…GH synthesis may be reduced, normal, or even increased in CKD [35]. GH secretion is normal or low in late pre-pubertal and pubertal children with CRF [36]; whereas GH secretion rates are increased with increased GH burst frequency in pre-pubertal children and in adults with end-stage renal disease (ESRD) [36][37][38]. The release of GH in response to GHRH is increased in adults [39], whereas, in children, the mid-to-late adolescent increase in GH production fails to occur in CKD [36].…”