Growth hormone prevents steroid-induced growth depression in health and uremia.
Treatment with supraphysiological doses of corticosteroids results in protein wasting and impairment of growth, whereas exogenous growth hormone (GH) causes anabolism and improvement of growth. We wanted to know whether the growth depressing effects of methylprednisolone (MP) are more expressed in an organism which is chronically diseased and whether these effects can be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH). MP in doses from 1 to 9 mg/kg/day caused a dose dependent reduction of length gain, weight gain and weight gain/food intake ratio in 140 g healthy female Sprague-Dawley rats. Food intake was not affected by MP. This points to a change in food metabolism as a mechanism for growth impairment. In addition, treatment with MP inhibited endogenous GH secretion, documented by serum GH concentration profiles over seven hours, decreased IGF-1 serum concentration and disturbed growth cartilage plate architecture. Concomitant treatment with 2.5 to 20 IU/rhGH/kg/day prevented the negative effects of MP on growth in a dose dependent manner and normalized growth plate architecture. In uremic rats in which food efficiency and growth was already reduced, 6 mg MP/kg/day further decreased length gain and prevented weight gain completely by bringing the weight gain/food conversion ratio to the nadir. All effects of MP including reduction of muscle mass could be prevented by concomitant treatment with 10 IU rhGH/kg/day. The effects of MP and rhGH on food efficiency and growth in uremic animals were numerically nearly identical to those in pair fed ad libitum fed controls, but this may be more relevant in the diseased organism in which basal growth is already suppressed.
Kovàcs
G
G
Division Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
Fine
R N
RN
Worgall
S
S
Schaefer
F
F
Hunziker
E B
EB
Skottner-Lindun
A
A
Mehls
O
O
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006130:Growth Disorders / Q000209:etiology / Q000517:prevention & control*; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D008775:Methylprednisolone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014511:Uremia / Q000150:complications / Q000188:drug therapy / Q000473:pathology
D013006:Growth Hormone; D008775:Methylprednisolone