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Biomedical subjects

J M Gertner

Publications and source records attributed to J M Gertner.

At least 19 recordsLinked to original sources
PubMed1992

Abnormal 1,25-dihydroxyvitamin D metabolism in preeclampsia.

We previously reported that preeclampsia is associated with hypocalciuria (N Engl J Med 1987; 316:715). The purpose of this study was to determine whether alterations in calcium regulatory hormones are present in preeclampsia and, if so, whether they are responsible for hypocalciuria. Thirty-two pregnant women were studied in the second and third trimesters of pregnancy (11 women with preeclampsia, nine with chronic hypertension, and 12 normotensive women). 1,25-Dihydroxyvitamin D, C-terminal parathyroid hormone, ionized calcium, and urinary calcium excretion were measured. 1,25-Dihydroxyvitamin D was significantly lower in the women with preeclampsia in the third trimester when the disease developed (37.8 +/- 15 pg/ml) than in women with chronic hypertension (75 +/- 15 pg/ml, p less than 0.05) and normal women (65 +/- 10 pg/ml, p less than 0.05). Parathyroid hormone was higher, but not significantly, in those with preeclampsia. Ionized calcium was not significantly different among the three groups. Urinary calcium excretion was abnormally low for pregnancy (less than 50 mg/24 hr) in all but one women with preeclampsia. We conclude that 1,25-dihydroxyvitamin D is reduced in preeclampsia and may lead to hypocalciuria by causing decreased intestinal absorption of calcium, stimulation of parathyroid hormone, and increased distal renal tubular resorption of calcium. The cause of reduced 1,25-dihydroxyvitamin D in preeclampsia is unknown and may be due to either diminished renal or placental production of the hormone.

Calcitriol↗
PubMed1992

Growth hormone actions on fat distribution and metabolism.

The secretion of growth hormone (GH) and the mass and distribution of body fat are linked through a complex series of interactions. There is increasing evidence that a GH/fat cycle exists and that elements of this cycle may possess regulatory functions. The essential elements of the cycle are: (1) GH-deficient individuals are often obese and lose body fat when they are treated; GH is lipolytic in vitro and causes an acute release of free fatty acids (FFA) when administered in vivo; (3) circulating FFA inhibit the pituitary release of GH by most secretagogues, including growth hormone releasing hormone, and (4) the obese state is characterized by a defect in GH release which can be reversed by weight loss.

Adipose Tissue↗
PubMed1992

Effects of systemic growth hormone (GH) administration on regional adipose tissue in children with non-GH-deficient short stature.

Chronic administration of exogenous GH to GH-deficient children is associated with a selective depletion of the abdominal sc fat depot and a resultant relative increase in gluteal, relative to abdominal, adipocyte lipid content. In GH-deficient children, the degree of this change in relative lipid content per adipocyte appears to be correlated with decreases in sensitivity of abdominal subcutaneous fat to the antilipolytic action of insulin. We studied abdominal and gluteal sc adipose tissue from 10 children with short stature (height less than 5% ile, growth velocity less than 5 cm/yr, bone age delayed at least 2 yr), who were not GH deficient based upon provocative testing (non-GH-deficient short stature) 1) before beginning and 2) after 3 months of therapy with exogenous GH (Humatrope, 0.1 mg/kg sc 3 times/week). In abdominal and gluteal adipocytes, we measured lipid content, rates of reesterification of fatty acids released by ongoing lipolysis and rates of in vitro lipolysis and lipogenesis in response to insulin, adenosine, and various adrenoreceptor agonists. These biochemical measures were correlated with measures of statural growth and adipose tissue distribution in each subject. We found that GH therapy was associated with a significant reduction in abdominal adipocyte size (0.48 microgram +/- 0.08 lipid per cell prior to therapy vs. 0.43 microgram +/- 0.08 lipid per cell after therapy, P less than 0.05) and a significant increase in responsiveness of gluteal sc adipose tissue to the lipogenic actions of insulin. The significant correlations of changes in abdominal adipocyte volume with changes in regional adipose tissue insulin sensitivity that were noted in GH-deficient children were not noted in this subject population, perhaps due to effects of endogenous GH on pretreatment insulin responsiveness of adipose tissue. These data reaffirm that GH has site-specific effects on regional adipose tissue depots.

Abdomen↗
PubMed1992

Insulin insensitivity in adrenal hyperplasia due to nonclassical steroid 21-hydroxylase deficiency.

To determine whether hyperandrogenism caused by an inborn error of adrenal steroidogenesis could produce insulin resistance, we examined insulin sensitivity in females with 21-hydroxylase deficiency. Minimal modelling was used to analyze the results of tolbutamide-modified, frequently sampled, iv glucose tolerance testing. Insulin sensitivity [Si; (min-1) (microU/mL)-1] was plotted against body mass index (BMI; defined as kilograms per m2). Six patients with nonclassical 21-hydroxylase deficiency (mean age, 27 yr; mean BMI, 23.2) underwent testing. None of these patients was in active puberty, nor was any patient being treated with glucocorticoids at the time of the study. Twelve eumenorrheic nonhyperandrogenic young adult female control subjects (mean age, 27 yr; mean BMI, 22.4) were also tested. The basal 17-hydroxyprogesterone concentration, but not the total serum testosterone level, was significantly different in the two groups (mean +/- SEM, 11,987 +/- 2,761 vs. 4,059 +/- 802 pmol/L; P < 0.05). As a group the patients' Si values were significantly lower than those of the controls (mean +/- SEM, 4.1 +/- 0.6 vs. 9.7 +/- 1.2; P < 0.05). There was no correlation between Si and basal serum 17-hydroxyprogesterone, testosterone, delta 4-androstenedione, or dehydroepiandrosterone. We conclude that chronic hypersecretion of androgen precursors due to an inborn error of metabolism can induce a reduction in insulin sensitivity.

Adolescent↗
PubMed1991

Growth hormone therapy in hypophosphatemic rickets.

The effects of growth hormone therapy on the biochemical measures of bone metabolism were studied in 11 children aged 3.5 to 17 years who had familial hypophosphatemic rickets; five were male. Subjects were maintained on a regimen of stable doses of conventional therapy (calcitriol and phosphate). Subjects were studied at baseline receiving conventional therapy and during three sequential treatment periods: no therapy (4 weeks), growth hormone only (0.05 mg/kg per day for 4 weeks), and conventional therapy plus growth hormone (2 weeks). The nine youngest subjects were continued on a regimen of triple therapy for an additional 24 weeks. Serum phosphate averaged 0.93 +/- 0.13 mmol/L (mean +/- SD) at entry and decreased when the subjects were not receiving any therapy. During the 4 weeks of growth hormone only treatment, phosphate rose in all 11 subjects (0.70 +/- 0.08 mmol/L to 0.83 +/- 0.08 mmol/L). With triple therapy, phosphate remained higher than with no therapy. Calcitriol, osteocalcin, and parathyroid hormone increased as the subjects received growth hormone alone. Insulinlike growth factor I z scores rose significantly in response to growth hormone therapy alone. All nine subjects receiving 6 months of triple therapy increased their growth rate z scores. Exogenous growth hormone therapy may be useful in familial hypophosphatemic rickets.

Adolescent↗
PubMed1990

Disorders of calcium and phosphorus homeostasis.

Calcium and phosphorus are, respectively, the fifth and sixth most abundant elements in the body; both play vital roles in a multitude of physiologic systems. Because the great bulk of these elements is found in the skeleton, a large part of the discussion of calcium and phosphorus metabolism focuses on skeletal disorders, the impact of which falls heavily on young children. This article reviews the physiology of calcium and phosphorus, the skeletal and systemic consequences of disorders of vitamin D nutrition and metabolism, and the metabolic bone disease of prematurity.

Bone Diseases, Metabolic↗
PubMed1990

Calcium, parathyroid hormone, and vitamin D in the "prehypertensive" Dahl salt-sensitive rat.

The purpose of this study was to determine if alterations of calcium and calcium regulating hormones precede the onset of NaCl-induced hypertension in the Dahl salt-sensitive (S) rat. After a 5-day balance study, serum ionized calcium, parathyroid hormone (PTH), and 1,25-dihydroxy vitamin D concentrations were measured in Dahl-S and salt-resistant (R) rats that had been maintained on a "normal" (1%) or high (7%) NaCl intake. Blood pressure was higher in Dahl-S than Dahl-R (P less than .01), but was not affected by 5 days of high NaCl. On both NaCl intakes, urine calcium excretion was increased, serum calcium was decreased, and serum PTH and 1,25 dihydroxy vitamin D were increased in Dahl-S compared to Dahl-R (P less than .01). On the high NaCl intake, fecal calcium was greater in Dahl-S than in Dahl-R, and net 5-day calcium balance was less positive in Dahl-S (P less than .05). Thus, alterations of calcium, PTH, and vitamin D precede NaCl-induced hypertension in Dahl-S. These alterations may contribute to the development of hypertension in this animal model.

Animals↗
PubMed1990

Pyridostigmine does not reverse dexamethasone-induced growth hormone inhibition.

Glucocorticoids inhibit the growth hormone (GH) response to a variety of stimuli, including GH-releasing hormone (GHRH) in vivo, but they increase GHRH-stimulated GH secretion when added, in vitro, to animal and human pituitary cells. This discrepancy has led to the hypothesis that glucocorticoids act in vivo by increasing somatostatin secretion from the hypothalamus. To examine this hypothesis, we used a cholinergic drug, pyridostigmine (PD), which reduces hypothalamic somatostatin secretion. Eight normal volunteers were studied. They underwent four tests: (1) GHRH test; (2) Dex + GHRH (GHRH test after treatment the night before, with dexamethasone (Dex)); (3) PD + GHRH; (4) Dex + PD + GHRH. Dex significantly inhibited the GH response to GHRH expressed as area under the GH/time curve (AUC, microgram/1/min) (mean +/- SEM = 895.2 +/- 196.6 vs 1970.9 +/- 600.1, P less than 0.05). PD significantly increased the AUC of GH secretion in PD + GHRH compared with GHRH alone (3541.2 +/- 571.3 vs 1970.9 +/- 600.1, P less than 0.01) but by no means restored completely the normal GH response to GHRH, when given to Dex-pretreated subjects. Furthermore, the mean AUC of Dex + PD + GHRH was significantly lower than that of PD + GHRH (1621.7 +/- 500.6 vs 3541.2 +/- 571.3, P less than 0.01), demonstrating that Dex continues to exert its inhibitory effect on GH secretion in the presence of PD. These results suggest that glucocorticoid-induced GH inhibition does not act solely through an increase in hypothalamic somatostatin secretion.

Adult↗
PubMed1990

Permissive action of growth hormone on the renal response to dietary phosphorus deprivation.

Animal studies have shown that GH is necessary for the increased renal production of calcitriol during dietary phosphorus deprivation (PD). These studies suggest that this adaptive change in vitamin D metabolism is mediated through insulin-like growth factor-I (IGF-I) and/or insulin. We subjected 16 GH-deficient children to 96 h of severe dietary PD twice, first before and again during recombinant GH replacement. Half of the children received low dose and half received high dose replacement with recombinant GH. We measured renal tubular reabsorption maximum for phosphate corrected for glomerular filtration rate (TmP/GFR), PTH, IGF-I, calcidiol, and calcitriol pre- and postdietary PD, both off and on GH. We also assessed insulin secretion during an oral glucose load (OGTT) off and on GH. Basal PTH, calcidiol, calcitriol, and fasting blood sugar were unaffected by GH therapy. PD did not affect PTH or calcidiol either off or on GH. Basal TmP/GFR rose on GH therapy (4.8 +/- 0.2 to 6.3 +/- 0.4 mg/dL) and with PD (4.8 +/- 0.2 to 5.7 +/- 0.2 mg/dL off and 6.3 +/- 0.4 to 7.8 +/- 0.3 mg/dL on GH). The increments due to PD and GH therapy were additive. The increments on GH were independent of the GH dose. Before GH replacement, calcitriol did not rise during PD (22.3 +/- 2.1 to 23.3 +/- 1.9 pg/mL), but during GH therapy, PD caused a significant rise in calcitriol (23.8 +/- 2.5 to 33.3 +/- 2.4 pg/mL; P less than 0.0001). The increment in calcitriol during PD was significantly greater in the high dose than it was in the low dose group (11.7 +/- 1.5 vs. 7.2 +/- 1.6 pg/mL; P less than 0.05). GH therapy caused a rise in the IGF-I level that was significantly greater in the high dose (0.26 +/- 0.03 to 3.15 +/- 0.56 U/mL) than in the low dose (0.27 +/- 0.02 to 0.68 +/- 0.13 U/mL) group. Insulin in response to OGTT was significantly greater after GH therapy (4155 +/- 600 microU/mL.min off GH; 6504 +/- 1153 microU/mL.min on GH), although there was no difference between the low and high dose groups. Regression analysis demonstrated a correlation between the change in calcitriol during PD and the IGF-I level (r = 0.83). There was no correlation between insulin levels and the change in calcitriol or between IGF-I or insulin levels and the increment in TmP/GFR during GH therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1990

Osteogenesis imperfecta.

Osteogenesis imperfecta describes a group of heritable disorders characterized by excessive bony fragility and reduced skeletal mass. It is classified in terms of its clinical manifestations, but our understanding of the underlying genetic defects in collagen synthesis is increasing rapidly. The nonoperative and surgical orthopedic approaches to osteogenesis imperfecta aim at the maximum preservation of limb strength and the correction of deformities. Various pharmacologic agents have been administered to patients with osteogenesis imperfecta, but to date, none have proved effective in controlled trials. Prenatal diagnosis has been attempted and seems certain to assume greater importance as knowledge of the molecular genetic basis of the disease increases.

Child↗
PubMed1989

Acute inhibition of somatotroph response to human growth hormone-releasing hormone 1-44 occurs following three hours but not one hour of growth hormone infusion.

Our previous studies have demonstrated that a short-term (three hour) infusion of methionyl human growth hormone (met-hGH, 2 micrograms/kg/h) is associated with a rise in serum concentrations of free fatty acids and glycerol, and a blunting of somatotroph response to human growth hormone releasing hormone 1-44 (GRH) in normal volunteers. To gain more information on the time course of this blunting, and to determine whether it could be temporally dissociated from the GH-induced rise in serum concentrations of lipolytic products, the response to GRH (0.3 micrograms/kg) was measured in five normal adult volunteers from hours 1.0 to 3.5 of a 3.5-hour infusion of saline or met-hGH 2 micrograms/kg/h. Somatotroph response to the same dose of GRH from hours 3.0 to 5.5 of a longer (5.5-hour) infusion of saline or met-hGH (2 micrograms/kg/h) in five other volunteers was used for comparison. There was a significant blunting of somatotroph response following three hours, but not one hour of met-hGH infusion. The longer infusion was associated with a significant rise in serum concentrations of free fatty acids, and the shorter met-hGH infusion was too brief to provoke such a rise. Neither met-hGH infusion was associated with a significant rise in serum concentrations of glycerol, insulin, glucose, or insulin-like growth factors (IGF). This study provides further evidence that there is an association between circulating FFA and somatotroph function and suggests that FFA may act as messengers, which provide information to central systems regarding the energy balance of the organism.

Adult↗
PubMed1989

Recombinant growth hormone enhances muscle myosin heavy-chain mRNA accumulation and amino acid accrual in humans.

A potentially lethal complication of trauma, malignancy, and infection is a progressive erosion of muscle protein mass that is not readily reversed by nutritional support. Growth hormone is capable of improving total body nitrogen balance, but its role in myofibrillar protein synthesis in humans is unknown. The acute, in situ muscle protein response to an infusion of methionyl human growth hormone was investigated in the limbs of nutritionally depleted subjects during a period of intravenous refeeding. A 6-hr methionyl growth hormone infusion achieved steady-state serum levels comparable to normal physiologic peaks and was associated with a significant increase in limb amino acid uptake, without a change in body amino acid oxidation. Myosin heavy-chain mRNA levels, measured by quantitative dot blot hybridization, were also significantly elevated after growth hormone administration. The data indicate that methionyl growth hormone can induce intracellular amino acid accrual and increased levels of myofibrillar protein mRNA during hospitalized nutritional support and suggest growth hormone to be a potential therapy of lean body wasting.

Adult↗
PubMed1989

Calcium and calcium regulating hormones in the "prehypertensive" Dahl salt sensitive rat (calcium and salt sensitive hypertension).

The purpose of this study was to determine if alterations of calcium and calcium regulating hormones precede the onset of NaCl induced hypertension in the Dahl salt sensitive (S) rat. After a 5 day balance study, serum ionized calcium, PTH, and 1,25 dihydroxy vitamin D concentrations were measured in Dahl-S and salt resistant (R) rats that had been maintained on a "normal" (1%) or high (7%) NaCl intake. Blood pressure was higher in Dahl-S than R (P less than .01), but was not affected by 5 days of high NaCl. On both NaCl intakes, urine calcium excretion was increased, serum calcium was decreased, and serum PTH and 1,25 dihydroxy vitamin D were increased in Dahl-S compared to Dahl-R (P less than .01). On the high NaCl intake, fecal calcium was greater in Dahl-S than in Dahl-R, and net 5 day calcium balance was less positive in Dahl-S (P less than .05). In contrast to NaCl, a high dietary intake of sodium with anions other than chloride (NaAA) fails to produce hypertension in the Dahl-S rat. NaAA loading resulted in decreased urine calcium excretion (P less than .01), and after 5 days of the high NaAA diet, serum calcium and PTH did not differ in Dahl-S and Dahl-R. Thus, alterations of calcium, PTH, and vitamin D precede NaCl-induced hypertension in Dahl-S. These alterations may contribute to the development of hypertension in this animal model.

Animals↗
PubMed1989

Intravenous refeeding blocks growth hormone (GH)-provoked rises in serum free fatty acids and blunting of somatotroph response to GH-releasing hormone in normal men.

We measured the serum GH responses to GHRH (1 micrograms/kg) in six normal men who had been rendered hyperinsulinemic and hypolipidemic by 10 days of total parenteral nutrition (TPN subjects) with a 25% dextrose-amino acid solution. The men underwent GHRH testing after 3 h of infusion of NaCl or Met-human (h) GH (2 micrograms/kg.h). The results of these tests were compared with those of five men tested in the post-absorptive state (PA subjects). The serum GH response to GHRH during NaCl infusion was significantly lower in the TPN subjects than in the PA subjects. During the Met-hGH infusion, the serum GH response to GHRH in the PA subjects was significantly lower than that after the NaCl infusion, whereas in the TPN subjects the response was similar to that during the NaCl infusion. The mean integrated areas under the GH response-time curve after GHRH treatment were 3963 +/- 2086 min/micrograms.L following NaCl infusion and 413 +/- 64 min/micrograms.L following Met-hGH infusion in PA subjects; they were 1127 +/- 500 min/micrograms.L following NaCl infusion and 1456 +/- 682 min/micrograms.L during Met-hGH infusion in the TPN subjects. The Met-hGH infusions resulted in a significant increase in serum FFA concentrations in the PA, but not the TPN, subjects. These results suggest that hyperalimentation induces a metabolic background which inhibits GH secretion, as manifested by a diminished serum GH response to GHRH administered after NaCl infusion. The absent FFA response to Met-hGH infusion in the TPN subjects may explain why the Met-hGH infusion in them did not result in a reduced serum GH response to GHRH as occurred in the PA subjects. Hence, FFA may play an important role in the effects of short term Met-hGH infusion on GH secretion.

Adult↗
PubMed1989

Metabolic clearance rates of synthetic human growth hormone in children, adult women, and adult men.

The MCR of biosynthetic human GH was studied in 12 prepubertal children, 9 adult women, and 13 adult men. Subjects received a constant infusion of biosynthetic GH, and clearance was calculated by dividing the infusion rates by steady state serum concentrations of GH. We found that adult men have a significantly more rapid MCR of human GH than women (125.2 +/- 7.6 mL/min.m2 in men; 89.4 +/- 7.7 mL/min.m2 in women) and that both men and women have a significantly more rapid MCR of human GH than prepubertal children (66.8 +/- 7.7 mL/min.m2). Sex differences in GH clearance rates may account at least in part for the lower mean serum GH concentrations in pubertal, but not prepubertal, males compared to those in females. The differences in clearance between prepubertal children and adult women and men suggest that the male-female differences in GH clearance are due to androgen effects on GH clearance or on the relative proportions of free and protein-bound GH in serum.

Adult↗
PubMed1989

Effects of systemic growth hormone (GH) administration on regional adipose tissue distribution and metabolism in GH-deficient children.

Chronic administration of exogenous GH to GH-deficient children is associated with a redistribution of adipose tissue from an abdominal (android) to a more peripheral (gynoid) distribution. We studied abdominal and gluteal sc adipose tissue from seven GH-deficient children 1) before beginning and 2) after 3 months of therapy with exogenous GH (0.1 mg/kg, sc, three times per week). In abdominal and gluteal adipocytes, we measured lipid content and rates of in vitro lipolysis and lipogenesis in response to insulin and various adrenoreceptor agonists. These results were correlated with measures of statural growth and adipose tissue distribution in each subject. We found that GH therapy was associated with a significant reduction in abdominal adipocyte size (0.68 +/- 0.09 micrograms lipid/cell before therapy vs. 0.49 +/- 0.07 after therapy; P less than 0.05), a significant reduction in overall basal rates of lipogenesis (0.43 +/- 0.06 mumol [14C]acylglyceride synthesized/10(6) cells.2 h before therapy vs. 0.27 +/- 0.09 after therapy), and with variable desensitization of abdominal sc adipose tissue to the antilipolytic effect of insulin. The extent of this decrease in insulin action was significantly correlated with changes in abdominal adipocyte lipid content (r = 0.77; P less than 0.05), and with the changes in the anatomical distribution of fat during the study period (r = 0.97; P less than 0.001), as measured by the relative lipid content per adipocyte at each site. We conclude that the site-specific changes in adipose distribution during GH administration are due in part to anatomical site-specific GH-mediated changes in insulin responsiveness of adipose tissue and that exogenous GH therapy is associated with a decrease in de novo triglyceride synthesis in GH-deficient children.

Adipose Tissue↗
PubMed1989

Growth and final height in classical and nonclassical 21-hydroxylase deficiency.

Final height was evaluated in 47 patients with classical 21-hydroxylase treated since diagnosis, and in 29 patients with nonclassical (NC) 21-hydroxylase deficiency who had never been treated before reaching final adult height. Classical patients achieved final heights consistently below the mean for the general population, and in all but four cases these patients also failed to attain the individual height expectation based on midparental height. Analysis of these results with regard to (1) clinical form (i.e. salt-wasting [SW] or simple virilizing [SV]) and (2) degree of hormonal control (i.e. good or poor) indicates that neither factor seems to affect the height outcome. Final height in NC patients, while significantly greater than for classical patients, was below the general population mean, and individual final heights were also significantly below expectation based on midparental height. In another group of NC patients who were still growing, some of whom were on courses of treatment and some under observation only, height at the time of diagnosis was compared with the most recent height prediction. Reduction of growth potential appeared to be somewhat lessened in the treated group, from which we tentatively suggest that treatment should be considered in NC patients even in the absence of clinical signs of androgenism.

Adolescent↗