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.
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).


METHODS
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: triple-blind crossover study of 9 healthy TS adolescents randomized to treatment with placebo, GH or GH+17beta-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 17beta-estradiol and norethisterone and compared with age-matched controls (n=24).


METHODS
Measurement of MBL, SP-D, DBP, and other inflammation markers.


RESULTS
Study 1: the levels of MBL (P=0.002) and SP-D (P=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=0.017). Study 2: treatment with GH increased MBL (P=0.045) and SP-D (P=0.05) concentrations in TS, while treatment with GH+17beta-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.


CONCLUSIONS
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.
Gravholt
Claus Højbjerg
CH
Medical Department M (Endocrinology and Diabetes) and Medical Research Laboratories, Arhus Kommunehospital, Arhus University Hospital, 8000 Arhus C, Denmark. ch.gravholt@dadlnet.dk
Leth-Larsen
Rikke
R
Lauridsen
Anna Lis
AL
Thiel
Steffen
S
Hansen
Troels Krarup
TK
Holmskov
Uffe
U
Naeraa
Rune Weis
RW
Christiansen
Jens Sandahl
JS
D000293:Adolescent; D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004958:Estradiol / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D006242:Haptoglobins / Q000378:metabolism; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D037601:Mannose-Binding Lectin / Q000097:blood*; D008875:Middle Aged; D009640:Norethindrone / Q000627:therapeutic use; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood*; D014168:Transferrin / Q000378:metabolism; D014424:Turner Syndrome / Q000097:blood* / Q000188:drug therapy*; D014809:Vitamin D-Binding Protein / Q000097:blood*
D006242:Haptoglobins; D037601:Mannose-Binding Lectin; D037663:Pulmonary Surfactant-Associated Protein D; D014168:Transferrin; D014809:Vitamin D-Binding Protein; D019382:Human Growth Hormone; D004958:Estradiol; D002097:C-Reactive Protein; D009640:Norethindrone