Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A.

Abstract

Objective: GH deficiency (GHD) in adults is associated with adverse effects on metabolism and increased cardiovascular risk. Pregnancy-associated plasma protein-A (PAPP-A) is a protease that promotes IGF-I availability in vascular tissues. PAPP-A levels appear to correlate with carotid intima-media thickness and have been proposed as an early predictor of cardiac events. The aim of our study was to evaluate PAPP-A levels in GHD adults at baseline and after GH replacement and correlate them with changes in body composition, lipid profile, glucose homeostasis, inflammatory markers and in leptin and adiponectin. Patients and methods: Fourteen GHD adults were evaluated at baseline and after 1 year of GH therapy. All patients were compared at baseline with 28 age-, sex-and body mass index (BMI)-matched control subjects. Results: At baseline, GHD adults showed higher PAPP-A levels (PZ0.03) and higher leptin (PZ0.04), fibrinogen (PZ0.002) and highly sensitive C-reactive protein (PZ0.01) values than controls. Therapy with GH reduced PAPP-A (PZ0.03) and fibrinogen levels (PZ0.002) while increased BMI (PZ0.01) and reduced waist-hip ratio (WHR; PZ0.05) were observed. Insulin and homeostasis model assessment of insulin resistance index increased after treatment (P!0.004/PZ0.007), without changes in leptin or adiponectin levels. PAPP-A values correlated positively with BMI and WHR and negatively with adiponectin before and after treatment, with no correlation with glucose homeostasis parameters, lipid profile or leptin. Conclusions: Our study suggests that PAPP-A expression is increased in GHD adults, and that 1 year of GH replacement therapy is able to reduce PAPP-A levels in this population. However, further studies are required to determine whether this decrease correlates with an improvement in atherosclerosis.European Journal of Endocrinology 158 483-490

Impact of adult growth hormone deficiency on metabolic profile and cardiovascular risk [Review]

“…Further studies will be needed in order to evaluate the effectiveness of GH treatment in decreasing cardiovascular risk in GHD. Moreover, it has been shown that values of pregnancy-associated plasma protein A (PAPP-A), a metalloproteinase secreted by artery smooth muscle cells and commonly used as an atherosclerosis marker, are increased in GHD patients compared to healthy controls and are brought within normality range after GH replacement therapy [66]. Even the study by Joaquin et al confirmed the increase of PAPP-A and CRP levels in GHD [66]; that work seems to suggest the existence of a causal mechanism between the reduction of IGF-1 levels and the increase of PAPP-A, also leading to hypothesize that PAPP-A could have a role in the development of atherogenic process of GHD [67] (Fig.…”

Growth Hormone Deficiency in Prepubertal Children: Predictive Markers of Cardiovascular Disease

“…The most common example resides in the elevation of pregnancy-associated plasma protein A (PAPP-A) levels in GHD adults [21]. PAPP-A is a member of the matrix metalloproteinase family and it has been included among markers of CV risk being associated both with the presence of carotid atherosclerosis and acute coronary syndrome [7].…”

Serum leptin concentrations in adolescents and young adults with growth hormone deficiency

“…W badaniach in vivo przeprowadzonych na różnych gatunkach zwierząt obserwowano zarówno brak wpływu GH na ekspresję leptyny w adipocytach [33], jak i jego działa-nie pobudzające [31] lub hamujące [32]. Również doniesienia dotyczące wpływu niedoboru GH na stężenia LEP u ludzi nie są spójne [33][34][35][36][37][38][39][40][41]. Brakuje prac dotyczących zachowania się stężeń leptyny w grupie młodzieży i młodych dorosłych w tzw.…”

“…Z kolei inni badacze stwierdzili, że u dorosłych pacjentów z AO-GHD stężenia LEP we krwi są podwyższone w porównaniu z grupą osób zdrowych o podobnym BMI [38,39]. Różnice te okazały się także istotne po przeliczeniu uzyskanych wyników na zawartość procentową i masę tkanki tłusz-czowej badanych [39].…”

“…W badaniach przeprowadzonych na zwierzętach oraz u ludzi wykazano bowiem, że GH zwiększa ekspresję rozpuszczalnego receptora leptynowego, powodując spadek stężenia wolnej leptyny we krwi [38,50]. Można zatem przypuszczać, że w niedoborze GH stężenia wolnej leptyny we krwi wzrastają, co może świad-czyć o rozwoju leptynooporności [51].…”