Mariano Castro-Magana

Effects of zinc deficiency and castration on fatty acid composition and desaturation in rats

The effects of zinc deficiency and testosterone on fatty acid composition of plasma lipids and microsomes of liver, intestine and testes were studied. The activities of fatty acid desaturase (Δ6 and Δ5) in rat liver and testes were also measured. A significant decrease in the level of arachidonic acid was observed in plasma of normal rats fed the zinc-deficient diet. Castration significantly decreased arachidonic acid but increased 20∶3 fatty acid, which is negligible in normal rats. Testosterone and zinc administration restored arachidonic acid to normal values. Zinc deficiency does not significantly change the fatty acid profile in liver, but castration decreased both arachidonic and 22∶6 fatty acid. Intestinal mucosal microsomes showed that the predominant fatty acid in this tissue, palmitic acid, is independent of zinc status, whereas polyunsaturated fatty acids 18∶2 and 20∶4 were decreased by zinc-deficient diet or castration. Zinc deficiency sharply decreased 22∶5 fatty acid and to some extent, other polyunsaturated fatty acids in testis microsomes. These changes in fatty acids are in agreement with increased Δ9 desaturation and decreased Δ5 desaturase activity. In testes, both Δ6 and Δ5 desaturase activities are decreased in zinc deficiency. It appears that zinc influences the conversion of linoleic to arachidonic acid, whereas testosterone influences Δ6 desaturase activity. The data suggest that zinc deficiency may be one of the important factors in the causation of polyunsaturated fatty acid deficiency, which in turn, may induce serum hypertriglyceridemia.

Final adult height in children with Prader-Willi syndrome with and without human growth hormone treatment.

Short stature is characteristic of children with Prader–Willi syndrome (PWS). While previous studies have demonstrated acceleration of linear height velocity with growth hormone (GH) treatment, the long‐term benefit on final adult height (AH) has not been reported. The objective of this study was to compare AH attained in PWS subjects with and without GH treatment. We reviewed the records of 21 children (aged 8.3u2009±u20092.7 years) with PWS and confirmed GH deficiency that attained AH after receiving human GH treatment (0.25u2009±u20090.06 mg/kg/week) for a period of 7.9u2009±u20091.7 years. A group of 39 non‐GH‐treated adults with matched initial height standard deviation score (SDS) at age 6.8u2009±u20091.3 years was used as control. In the GH‐treated group the mean initial height and AH‐SDS was −1.9u2009±u20091.7 and −0.3u2009±u20091.2 respectively (Pu2009<u20090.0001), whereas the mean initial and AH‐SDS in the control group was −1.9u2009±u20091.3 and −3.1u2009±u20091 respectively (Pu2009<u20090.0001). Scoliosis was seen in 43% and 39% in the GH‐treated and control group respectively. Premature adrenarche (PA) was noticed in 57% of GH‐treated group. Six subjects in the control group but none of the GH‐treated subjects developed type 2 diabetes mellitus. Our data show that administration of GH to children with PWS restores linear growth and final AH without significant adverse effects other than PA. Further studies will be necessary to determine related morbidity and mortality in individuals with PWS that reached final AH with or without GH treatment.

Zinc deficiency-induced changes in the composition of microsomal membranes and in the enzymatic regulation of glycerolipid synthesis

The effects of zinc deficiency and/or castration on the lipid composition of microsomal membranes of liver, small intestine and testes were studied in rats. The results showed that feeding a zinc-deficient diet to castrated rats decreased phospholipid content and consequently increased the cholesterol-to-phospholipid ratio in liver microsomes. An increase in cholesterol-to-phospholipid ratio occurred also in small intestine and testes microsomes from rats fed the zinc-deficient diet. It is postulated, therefore, that zinc deficiency alters the lipid composition and fluidity of microsomal membranes. Zinc deficiency also affected the activities of the enzymes involved in the formation of triglycerides and phospholipids. There was a large increase in total and specific activity of phosphatidate phosphatase and the changes in the total activity of choline phosphotransferase correlated well with the changes observed in serum or liver triglycerides and phospholipids. Stearoyl CoA desaturase, which is a control enzyme for hepatic lipogenesis, was also increased by more than 200% in zinc-deficient states, as was the diglyceride content of hepatic microsomes. These results indicate that the increased synthesis of triglycerides and phospholipids in zinc deficiency may be due to the increased availability of substrates as well as to increased activities of the enzymes involved in these processes.

Effect of prolonged clonidine administration on growth hormone concentrations and rate of linear growth in children with constitutional growth delay

Sixteen prepubertal children with constitutional growth delay (10 boys and six girls, mean age 7.2 +/- 2.1 years) were administered a daily dose of clonidine (0.15 mg/m2) for a period of 1 year. Growth hormone levels, plasma somatomedin C, and linear growth rate were significantly increased at the end of the treatment. Six of the children maintained the higher growth rate even 6 months after treatment. These and other studies suggest that prolonged stimulation of the hypothalamus by clonidine may ameliorate the impairment of growth hormone release seen in some children with constitutional growth delay. Because of the low cost and the convenience of the oral route, administration of clonidine could be a mode of treatment in some children with poor growth.

Improvement of Leydig cell function in male adolescents after varicocelectomy

The incidence of varicoceles in adolescent boys has been reported to range from 5.7% at 10 years of age to 19.3% at age 14 years, with a mean of 16.2% for the whole group of boys aged 10 to i9 years. Oster 1 found no varicoceles before the age of 10 years among 1072 Danish schoolboys. After adolescence, the incidence of varicoceles remains constant. Steeno et al. 2 reported that 81% of school-age adolescents with visible varicoceles already had a decrease in testicular volume, consistency, or both. In fact, a pantesticular defect involving testosterone production and spermatogenesis has been reported ~in adult men with varicoceles. 3 However, there have been no studies of the endocrine function of the testes in male adolescents. We studied the hypothalamicpituitary-testicular axis in five male adolescents, aged 17 to 20 years, with visible varicoceles. The effect of Varicocelectomy on the endocrine function of the testes was also evaluated. METHODS Patients. Our patients were five male adolescents, aged 17 to 20 years, who were seen in the pediatric endocrine clinic for evaluation of testicular function. All these patients had visible left-sided varicoceles, big enough so that the mass Of tortuous veins impeded examination of the testicle when the patients were in the upright position; the varicoceles were graded as severe. Two of these patients also had right-sided varicoceles graded as moderate, according to the classifica

425 EFFECTS OF TESTOSTERONE ON ZINC METABOLISM IN RATS

We have measured Zinc (Zn) levels in different tissues of castrated rats (CR) fed purified diet containing 100 pp Zn for 6 wks with and without injection of testosterone (T) enanthate (20 mg IM) 2 wks prior to sacrifice. CR had very low serum T (0.6 ± 0.1 ng/ml) as compared with the controls (8.2 ± 0.7 ng/ml) and T administration restored serum T to normal levels (9.1 ± 1.1 ng/ml).After castration, serum and tissue Zn levels were significantly decreased with concomitant increase in urinary Zn (see Table). Administration of T to CR increased the serum and tissue Zn levels almost to the normal level. Since food intake was similar in all groups, T in CR may have increased Zn retention. These results strongly suggest a positive relationship between Zn and T metabolism.

Zinc deficiency in achondroplastic children and their parents.

Using atomic absorption spectrophotometry, we have assayed zinc and copper concentrations in the hair of children with typical achondroplasia, familial short stature, or constitutional growth delay, and of unaffected parents of achondroplastic children and healthy adults of similar age and sex as the parents (Table). Specimens consisted of the terminal 2 to 3 inches of hair, obtained from the posterior scalp. Duplicate 60 to 80 mg hair specimens were digested in concentrated nitric:perchloric (3:1) acid mixture. The results are the mean of at least two determinations per specimen. The achondroplastic children were all confirmed as typical examples by physical examination and radiographs of skull, spine, long bones, and pelvis. Several of the parents were noted to have white flecks in their fingernails, which has been reported to be associated with zinc deficiency. The data indicate significantly reduced zinc and increased copper values, and reduced zinc:copper ratio, in the hair of parents and children with achondroplasia.

909 ZINIC LEVELS IU ONE CASE OF FETAL ALCOHOL SYNDROME

Concentration of zinc (Zn) in hair, urine and serum were measured by atomic absorption spectrophotometry in one 14-month old girl with typical features of Fetal Alcohol Syndrome (FAS) (peculiar facies, congenital malformations, pre and post natal growth deficiency). She was born to an alcoholic woman who continued drinking heavily throughout her pregnancy. Zinc level was low in hair (66 μg/g) and urine (266.8 μg/g of creatinine) but normal in serum(95 μg%), reflecting probable chronic depletion of Zn. (Normal values are: hair 193 ± 18 μg/g, serum 75-160 μg%, urine 400-600 μg/g.) It has been shown that the offspring of Zn-deficient rats have marked growth retardation and high incidence of congenital malformation, some of which are similar to those seen in FAS. Alcoholic patients have been found to lose increased amounts of zinc in urine. Therefore, it is tempting to speculate that congenital Zn deficiency plays an important role in the pathogenesis of this syndrome.

405 ZINC LEVELS IN CHILDREN WITH GROWTH RETARDATION

Concentration of zinc in hair and serum of children with short stature (familial or constitutional) was measured by atomic absorption spectrophotometry. Some of them were treated with methyltestosterone (MT), 10 mg. daily.Our Zn values were similar to those reported for normal children. Nevertheless, children receiving MT had higher Zn levels than the children without medication. Since Zn deficiency is associated with growth retardation, these results raise the question of whether increased Zn retention may be one of the mechanisms by which androgens accelerate growth. We were unable to find any significant difference between the Zn levels from children with familial short stature and those from children with constitutional growth delay.