title: 11β-Hydroxysteroid dehydrogenase type 1 activity in short small-for-GA children and in response to GH therapy.
abstract: Small for GA (SGA) children are at risk for developing the metabolic syndrome. Those who do not catch up, and remain short (SSGA), may benefit from GH therapy. 11β Hydroxysteroid dehydrogenase type 1 (11β-HSD-1) is expressed in visceral fat and is implicated in metabolic morbidity. We hypothesized that SSGA children will have increased basal and glucocorticoid (GC)-stimulated 11β-HSD-1 activity. Twenty SSGA children, aged 7.1 ± 1 y (mean ± SD), were studied before and while on GH therapy and compared with 12 normal age-matched controls. 11β-HSD-1 activity was evaluated by gas chromatography mass spectrometry (GCMS) of urinary steroid product/substrate ratios. GC-stimulated 11β-HSD-1 activity was assessed after overnight dexamethazone (DEX), by oral cortisone conversion to cortisol. In SSGA children, 11β-HSD-1 activity was lower (p < 0.05) and GC-stimulated activity enhanced. SSGA children had maximal cortisol generation of 883 ± 108 compared with 690 ± 63 nmol/L in controls (p < 0.04). GH treatment suppressed 11β-HSD-1 activity. GC-stimulated enzyme activity correlated negatively with GA (r = -0.53, p < 0.01) and birth weight (r = -0.55, p < 0.01). SSGA is associated with enhanced GC-stimulated 11β-HSD-1 activity. This may be programmed in utero, as it is not a function of body composition or secondary metabolic derangement. GH therapy normalizes GC-stimulated 11β-HSD-1 activity.
authors.affiliation: Pediatric Endocrinology, Meyer Children's Hospital, Haifa 31096, Israel. zuckerln@netvision.net.il
authors.forename: Nehama
authors.initials: N
authors.lastname: Zuckerman-Levin
authors.forename: Larisa
authors.initials: L
authors.lastname: Tsivlin
authors.forename: Carlos
authors.initials: C
authors.lastname: Knopf
authors.forename: Oshrat
authors.initials: O
authors.lastname: Flor
authors.forename: Zila
authors.initials: Z
authors.lastname: Shen-Orr
authors.forename: Moshe
authors.initials: M
authors.lastname: Levin
authors.forename: Ze'ev
authors.initials: Z
authors.lastname: Hochberg
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000378:metabolism* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone; D008401:Gas Chromatography-Mass Spectrometry; D005938:Glucocorticoids / Q000378:metabolism; D006130:Growth Disorders / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D019382:Human Growth Hormone; D003907:Dexamethasone; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone