Hypothalamic growth hormone-releasing hormone (GHRH) cell number is increased in human illness, but is not reduced in Prader-Willi syndrome or obesity.
BACKGROUND
Acute illness leads to increased GH, but reduced IGF-I secretion, while both are reduced in chronic illness. Prader-Willi syndrome (PWS) is a genetic obesity syndrome, with GH deficiency a feature independent of obesity. Reduced GH secretion may result from decreased hypothalamic release of GH-releasing hormone (GHRH).


OBJECTIVE
To quantify hypothalamic GHRH neurone cell number in control subjects with various lengths of premorbid illness duration, PWS and non-PWS obese subjects.


METHODS
We examined GHRH neurones in the infundibular nucleus/median eminence complex of control subjects (n = 26, including four children), PWS (n = 6) and non-PWS (n = 4) obese adults and PWS children (n = 2), by quantitative immunocytochemistry, using postmortem material.


RESULTS
We found: (i) higher GHRH cell number during prolonged illness prior to death in both control adults (r = +0.62, P = 0.002, cell number vs. premorbid illness duration) and PWS adults (r = +0.90, P = 0.02); (ii) higher GHRH cell number in female than male adults [by 53% (95% confidence interval 28-83%) in controls, P = 0.005, correcting for premorbid illness duration]; (iii) no difference in GHRH cell number between PWS adults and control or non-PWS obese adults (P = 0.7 and P = 0.4, adjusting for sex and illness duration); and (iv) low GHRH cell number in only one PWS child (who had been receiving exogenous GH therapy).


CONCLUSIONS
These findings suggest continued activation of GHRH neurones during prolonged illness. There is no evidence that the GH deficiency in PWS results from reduced GHRH cell number, and GHRH neuronal responses to illness and exogenous GH treatment appear normal in PWS.
Goldstone
Anthony P
AP
Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research, Amsterdam, The Netherlands. tgoldstone@yahoo.com
Unmehopa
Unga A
UA
Swaab
Dick F
DF
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D016022:Case-Control Studies; D002452:Cell Count; D002908:Chronic Disease; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000737:chemistry*; D009765:Obesity / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000378:metabolism*; D012044:Regression Analysis; D013398:Sudden Infant Death
D013007:Growth Hormone-Releasing Hormone