The effects of GH and hormone replacement therapy on serum concentrations of mannan-binding lectin, surfactant protein D and vitamin D binding protein in Turner syndrome

Abstract

Objective: Studies in animals and humans indicate that growth hormone (GH) and insulin-like growth factor-I (IGF-I) modulate immune function. Recently, it was reported that GH therapy increased the level of mannan-binding lectin (MBL) in normal patients, and that treatment of acromegalics with pegvisomant decreased the levels of MBL. The effect on MBL was thought to be due to a specific action of GH, since IGF-I treatment did not affect MBL. Whether it is advantageous or not to have high or low levels of MBL is not known. Likewise, it is not clear how the modifications induced by GH affect immune function. In the present study we examined whether GH or hormone replacement therapy (HRT) in Turner syndrome (TS) influence the serum concentrations of MBL and two other proteins partaking in the innate immune defence, surfactant protein D (SP-D) and vitamin D binding protein (DBP). Design: Study 1: a double-blind crossover study of 12 healthy TS adolescents examined during treatment with either placebo or GH for 2 months, and compared with a control group. Study 2: tripleblind crossover study of 9 healthy TS adolescents randomized to treatment with placebo, GH or GH þ 17b-estradiol. Study 3: 60 adult TS patients (55 received HRT) compared with 59 age-matched controls. Study 4: 27 patients with TS were examined before and during sex hormone replacement with 17b-estradiol and norethisterone and compared with age-matched controls (n ¼ 24). Methods: Measurement of MBL, SP-D, DBP, and other inflammation markers. Results: Study 1: the levels of MBL (P ¼ 0.002) and SP-D (P ¼ 0.012) increased during GH treatment, whereas no changes were observed in comparison with controls. DBP was unchanged by GH, but was significantly higher in TS compared with controls (P ¼ 0.017). Study 2: treatment with GH increased MBL (P ¼ 0.045) and SP-D (P ¼ 0.05) concentrations in TS, while treatment with GH þ 17b-estradiol did not increase levels further. DBP was unchanged by treatment. Study 3: levels of MBL, SP-D, and DBP were similar in adult TS and control subjects. Study 4: DBP levels decreased in response to HRT, while MBL and SPD levels were unchanged. Levels of all three plasma proteins were similar to controls. Conclusion: We show that treatment with GH significantly increases MBL and SP-D concentrations in TS, while HRT marginally decreases DBP. Whether the present findings, suggesting a link between the endocrine and the immune system, have clinical consequences needs to be studied further. European Journal of Endocrinology 150 355-362

Body composition is distinctly altered in Turner syndrome: relations to glucose metabolism, circulating adipokines, and endothelial adhesion molecules

“…Combined with previous studies showing slightly elevated levels of CRP (18) and IL-6 (17), a picture of a chronic low-grade inflammatory state emerges. None of the cytokines were related to body composition.…”

“…Adhesion factors are secreted from endothelial cells and levels are increased in response to insults to the vasculature. A recent study has implicated an increased level of interleukin (IL) 6 in TS (17), and we have previously shown in different populations of females with TS that C-reactive protein (CRP) is discretely increased (18), pointing towards an activated inflammatory state.…”

Novel function of recombinant pituitary adenylate cyclase-activating polypeptide as stimulator of innate immunity in African catfish (Clarias gariepinus) fry

“…MBL mediates the lectin pathway of the complement system in mammals [50]. The hormonal regulation of mannan-binding lectin has been studied in humans [51,52]. These studies suggest that MBL synthesis in humans may be increased by thyroid hormone and GH.…”

Serum Levels of Mannose-Binding Lectin and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women

“…18,24 Endocrine status plays an important role in the regulation of MBL levels. 30,31 Hormonal differences and cardiovascular disease are an ongoing topic of research. Anti-inflammatory properties of estrogen have sparked much interest and may comprise complement activation.…”