Metabolic Effects of Human Growth Hormone and of Estrogens in Boys with Duchenne Muscular Dystrophy

Abstract

A B S T R A C T Metabolic balance studies were conducted in seven boys with Duchenne-type muscular dystrophy, and in six normal boys of similar age, during a 12 day control period and during a 12 day period of treatment with human growth hormone (HGH) at the following doses: 0.0168, 0.0532, and 0.168 U/kg body weight (BW)f per day (doses A, B, and C, respectively). In five of the six normals, dose C caused positive balances in N, P, Na, and K; doses B and A had anabolic effects in two and one normal subjects, respectively. In six of the seven Duchenne cases, dose C caused negative balances of N and K, and sometimes of P. Negative balances were produced in three of the Duchenne subjects by dose B, and in one by dose A. None of the dystrophy cases exhibited an anabolic response to any dosage of HGH tested.The release of endogenous HGH in response to insulin, after 2 days' pretreatment with diethylstilbestrol, was similar in both groups of subjects. In the course of these tests, a marked anabolic effect of diethylstilbestrol in the Duchenne patients was apparent. Therefore metabolic balance studies were repeated, in both Duchenne and normal cases, during a 12 day control period and during 12 days of treatment with diethylstilbestrol (0.106 mg/kg BW1 per day). In three of the normal children, diethylstilbestrol had no effect on the elemental balances; in two cases, a retention of Na was observed. In all seven Duchenne cases, diethylstilbestrol caused positive balances in N. P, Na, and K. Ethinyl estradiol (0.0106 mg/kg BW1 per day) produced positive N, P, Na, and

Metabolic Effects of Plasmin Digests of Human Growth Hormone in the Rat and Man

“…Significant effects on P, Na, and K balance occurred with less regularity: dose A was ineffective in three trials; dose B caused significant P, Na, and K retention in only zero, one, and one of eight subjects; dose C stimulated retention of these elements in four, six, and three of eight persons, respectively. Weight gain also occurred.2 Ratios of AN, ANa, and AK (36) showed about one-half the weight gain to represent protoplasm and about one-half extracellular fluid. Dose C of hGH caused a significant (P < 0.05) reduction in fasting plasma AAN at days 5-7 of the 7-day course of treatment in each of three subjects but did not alter fasting FFA level significantly.…”

Evolving Therapeutic Strategies for Duchenne Muscular Dystrophy: Targeting Downstream Events

“…An alternative approach for shifting dystrophin-deficient muscle toward a positive protein balance has tested whether systemic administration of growth factors can maintain muscle mass and function. Based on early success that showed exogenous GH can cause a positive nitrogen balance in myotonic dystrophy patients (18), the possibility that GH could have similar effects on DMD boys was tested (19). However, 12 d of GH treatment to seven DMD patients unexpectedly produced undesired, catabolic effects.…”

Responsiveness of Growth Hormone-Deficient Children to Human Growth Hormone EFFECT OF REPLACEMENT THERAPY FOR ONE YEAR

“…2). But the rate was highest (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) cm/yr) during the first 3-6 mo and then declined (0-8 cm/yr). In all six cases, the inflection in the growth curve occurred between 3 and 7 mo.…”

“…This was accompanied, moreover, by acute negative balance of other intracellular (K and P) and extracellular (Na) elements and by loss of body weight. From the ratios of the negative balances of N, P, Na, and K, it can be calculated (15) that the loss of body weight represented about 50% intracellular protoplasm and 50% extracellular fluid. These observations, although made in GHdeficient subjects during and after replacement treatment with exogenous GH, suggest that in normal individuals the endogenous hormone is indeed involved in the continuing regulation of protein and mineral metabolism.…”