Effect Of Growth Hormone Administration Research Articles

Effect of growth hormone administration on ameliorating pregnancy outcome in women with advanced maternal age and exploration of its optimized utilization.

Age-related fertility decay is a great challenge for clinicians. Growth hormone (GH) supplementation has been studied as an adjuvant since late 1980s. However, it has not come to a consensus on the GH administration due to the ambiguous efficacy among studies with different enrolled population and dosage regime. A self-controlled retrospective study was conducted on women with advanced maternal age who underwent at least a previous cycle without GH (GH-) and a subsequent cycle with GH co-treatment (GH+). The ovarian stimulation parameters and outcomes were compared between the two cycles and logistical analysis was applied to further explore the association between GH administration protocol as well as other clinical parameters and cumulative live birth in GH+cycle. A total of 150 women aged 35-43 were included. The number of oocytes retrieved, MII oocytes, 2PNs, transferrable embryos and good-quality embryos in GH+ significantly increased (p < 0.001). The proportion of cycles with no transferrable embryos was significantly reduced in GH+ cycle compared with previous GH- cycle (3 vs. 32; p < 0.001). GH co-treatment cycles showed significantly higher clinical pregnancy rates (43.75% vs. 6.06%; 38.35% vs. 12.04%, p < 0.001), live birth rates (29.17% vs. 0; 27.07% vs. 0, p < 0.001) in both fresh and frozen-thawed embryo transfer cycle. Cumulative live birth rate of the GH+ cycle reached 33.33%. Use of GH prior to Gn stimulation and lasting until the hCG day seemed to achieve a higher successful live birth rate (OR 2.312, 95%CI 1.074-5.163, p=0.032). GH supplementation could ameliorate pregnancy outcome in women with advanced maternal age. Dosage regimen of long-term pretreatment prior to Gn stimulation (4 IU every other day) and 4 IU per day until hCG day may of greater efficacy compared with concurrent administration with Gn. Additionally, it's worthy of exploring whether an individualized dosage regimen based on the IGF or IGFBP level of patient would be more reasonable and effective. More well-designed prospective trials with large sample size and fundamental experiments on the mechanism are required to testify findings above.

Abstract #1319148: Effect of Growth Hormone Administration in a Patient With Achondroplasia

Treatment of short stature in a patient with achondroplasia.

Effect of growth hormone administration on ICSI outcomes in patients with polycystic ovary syndrome and recurrent implantation failure: A retrospective cross-over study.

Recurrent implantation failure (RIF) may be observed in some young women with polycystic ovary syndrome (PCOS) after in-vitro fertilization (IVF) [1]. The observation that administration of growth hormone (GH) during ovarian stimulation may improve IVF outcomes, not only in women aged >40 years [2] but also in younger women with RIF [3], led us to consider the use of GH therapy in women with RIF, independently of their age.

Body fat distribution and circulating adipsin are related to metabolic risks in adult patients with newly diagnosed growth hormone deficiency and improve after treatment

ObjectiveThe relationships between body fat distribution, the adipokine adipsin and metabolic risks were assessed in patients with adult growth hormone deficiency (AGHD) before and after growth hormone (GH) treatment. MethodsSixty newly diagnosed AGHD patients were included in our study, 24 of whom were evaluated after at least one year of GH treatment. Anthropometric parameters, glucolipid metabolism and the adipokine adipsin were measured. Visceral adipose tissue (VAT) and body composition were evaluated using a dual-energy X-ray-absorptiometry (DXA) scanner. ResultsAt baseline, the higher VAT group had worse glucolipid metabolism parameters. Basal GH was negatively associated with VAT (r=-0.277, p = 0.045), while minimal correlations were found with fat mass depots, such as limbs and trunk fat (all p > 0.05). Adipsin was correlated with total body fat (r = 0.543, p < 0.001), VAT (r = 0.563, p < 0.001) and insulin resistance (r = 0.353, p = 0.006). The effect of GH administration on fat distribution was mainly reflected in the reduction in VAT. Partial improvements were found in lipid profiles, including increased high-density lipoprotein (HDL) and decreases in triglycerides (TGs) and lipoprotein(a), while glucose metabolism showed little change. The adipsin level also decreased significantly. The best predictors of VAT at baseline were trunk fat and IGF-I, and after treatment, VAT was predicted by decreased adipsin and an increase in lean mass. Conclusions(1) VAT is an important metabolic risk factor for AGHD patients. (2) GH treatment decreased body fat predominantly in the visceral and central fat depots. (3) The lipid profiles partially improved after treatment, while glucose metabolism showed little change.

The Effect of GH Administration on Oocyte and Zygote Quality in Young Women With Repeated Implantation Failure After IVF.

Growth hormone (GH) has been shown to improve implantation and live birth rates in women of >40 years of age treated by in vitro fertilization (IVF). This effect was initially attributed to a GH effect on oocyte quality, but later studies showed that GH can also improve uterine receptivity for embryo implantation. As to younger women with previous failures of embryo implantation after IVF, data reported in the literature are ambiguous. This retrospective study focused on this latter category of women, comparing the numbers and morphological appearance of oocytes recovered from women with two previous IVF failures, aged between 30 and 39 years and treated with GH, with a comparable group of women without GH treatment. These results were complemented with the analysis of morphological markers of zygote and embryo quality and IVF clinical outcomes in both groups. The oocytes, zygotes and embryos from women treated with GH showed better morphological scores, and their uterine transfer resulted in more implantations, pregnancies and live births, as compared with the untreated group. It is concluded that the improvement of IVF outcomes in women with previous repeated IVF failures by exogenous GH administration is, at least partly, related to an increase in oocyte developmental potential. The statistically evident improvement of oocyte and embryo quality is the main finding of this study. Its weakness is its retrospective nature.

Effect of Growth Hormone Administration on the Mass and Strength of Muscles in Healthy Young Adults: A Systematic Review and Meta-Analysis

The growth hormone (GH) is prohibited for use by athletes, while its anabolic effect on muscle tissue is still debated. The review provides a systematic evaluation of the GH effects on the body composition and strength parameters in well-trained healthy young subjects. A meta-analysis of published data from randomized controlled trials (RCTs) was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled results of 11 RCTs showed that GH administration significantly increases the lean body mass (2.72, 95% CI: 2.02; 3.38, p < 0.01), total water content (1.10, 95% CI: 0.54; 1.66, p < 0.01), and extracellular water (1.78, 95% CI: 1.04; 2.52, p < 0.01) and reduces the fat mass (–0.67, 95% CI: –0.93; –0.40, p < 0.01) without changing the muscle protein synthesis rate (0.00, 95% CI: –0.01; 0.02, p = 0.70) and muscle strength (–0.02, 95% CI: –0.05; 0.02, p = 0.36) as compared with placebo. A conclusion was made that GH administration can improve the body composition in healthy young subject by exerting a significant lipolytic effect without causing hypertrophy of muscle fibers. The increase in lean body mass is due to an accumulation of extracellular water.

The Effect of Growth Hormone Administration on the Regulation of Mitochondrial Apoptosis in-Vivo.

The purpose of this study was to determine whether recombinant human growth hormone (rhGH) would show any significant effects on the expression of apoptosis regulating proteins in peripheral blood mononuclear cells (PBMCs). Additionally, the potential for post-transcriptional regulation of gene expression by miRNA was assessed in two cellular compartments, the cytosol and the mitochondria. Ten male subjects were subcutaneously injected with either rhGH (1 mg) or saline (0.9%) for seven consecutive days in a double-blinded fashion. Blood sampling was undertaken prior to treatment administration and over a period of three weeks following treatment cessation. Bcl-2 and Bak gene and protein expression levels were measured in PBMCs, while attention was also directed to the expression of miR-181a and miR-125b, known translational inhibitors of Bcl-2 and Bak respectively. Results showed that rhGH significantly decreased Bak protein concentrations compared to placebo samples for up to 8 days post treatment. While cytosolic miRNA expression was not found to be significantly affected by rhGH, measurement of the expression of miR-125b in mitochondrial fractions showed a significant down-regulation eight days post-rhGH administration. These findings suggest that rhGH induces short-term anti-apoptotic effects which may be partially mediated through a novel pathway that alters the concentration of mitochondrially-associated miRNAs.

Tendon and skeletal muscle matrix gene expression and functional responses to immobilisation and rehabilitation in young males: effect of growth hormone administration

We examined the effect of growth hormone (GH) on connective tissue of tendon and skeletal muscle during immobilisation and re-training in humans. Young men (20-30 years; n = 20) were randomly assigned to daily recombinant human GH (rhGH) (33-50 μg kg(-1) day(-1)) or placebo (Plc), and had one leg immobilised for 2 weeks, followed by 6 weeks of strength training. The cross-sectional area (CSA), maximal muscle strength (maximal voluntary contraction, MVC) and biomechanical properties of the quadriceps muscle and patellar tendon were determined. Muscle and tendon biopsies were analysed for mRNA of collagen (COL1A1/3A1), insulin-like growth factors (IGF-1Ea/Ec), lysyl oxidase (LOX), matrix metalloproteases (MMP-2 and MMP-9), decorin and tenascin-C. Fibril morphology was analysed by transmission electron microscopy (TEM) to detect changes in the fibril diameter distribution. In muscle, CSA and MVC declined with immobilisation and recovered with rehabilitation similarly in both groups. Likewise, both groups showed increased IGF-1Ea/Ec and COL1A1/3A1 expression in muscle during re-training after immobilisation compared with baseline, and the increase was more pronounced when subjects received GH. The tendon CSA did not change during immobilisation, but increased in both groups during 6 weeks of rehabilitation (∼14%). A decline in tendon stiffness after immobilisation was observed only in the Plc group, and an increase during 6 weeks of rehabilitation was observed only in the GH group. IGF-1Ea and COL1A1/3A1 mRNA increased with immobilisation in the GH group only, and LOX mRNA was higher in the GH group than in the Plc group after immobilisation. Both groups showed an increase in MMP-2 with immobilisation, whereas no changes in MMP-9, decorin and tenascin-C were observed. The tendon fibril diameter distribution remained unchanged in both groups. In conclusion, GH stimulates collagen expression in both skeletal muscle and tendon, abolishes the normal inactivity-related decline in tendon stiffness and LOX, and results in increased tendon CSA and stiffness during rehabilitation. GH has a matrix-stabilising effect during periods of inactivity and rehabilitation in humans.

Effect of growth hormone administration to mature miniature Brahman cattle treated with or without insulin on circulating concentrations of insulin-like growth factor-I and other metabolic hormones and metabolites

Previously, we determined that a primary cause of proportional stunted growth in a line of Brahman cattle was related to an apparent refractoriness in metabolic response to GH in young animals. The objective of this study was to determine the effect of administration of GH, insulin (INS), and GH plus INS to mature miniature Brahman cows (n = 6; 9.7 ± 2.06 y; 391 ± 48.6 kg) and bulls (n = 8; 9.4 ± 2.00 y; 441 ± 54.0 kg) on circulating concentrations of metabolic hormones and metabolites, primarily IGF-I and IGF-I binding proteins. We hypothesized that IGF-I secretion could be enhanced by concomitant administration of exogenous GH and INS, and neither alone would be effective. Animals were allotted to a modified crossover design that included four treatments: control (CON), GH, INS, and GH + INS. At the start of the study, one-half of the cattle were administered GH (Posilac; 14-d slow release) and the other one-half served as CON for 7 d. Beginning on day 8, and for 7 d, INS (Novolin L) was administered (0.125 IU/kg BW) twice daily (7:00 AM and 7:00 PM) to all animals; hence, the INS and GH + INS treatments. Cattle were rested for 14 d and then were switched to the reciprocal crossover treatments. Blood samples were collected at 12-hour intervals during the study. Compared with CON, GH treatment increased ( P < 0.01) mean plasma concentrations of GH (11.1 vs 15.7 ± 0.94 ng/mL), INS (0.48 vs 1.00 ± 0.081 ng/mL), IGF-I (191.3 vs 319.3 ± 29.59 ng/mL), and glucose (73.9 vs 83.4 ± 2.12 mg/dL) but decreased ( P < 0.05) plasma urea nitrogen (14.2 vs 11.5 ± 0.75 mg/dL). Compared with INS, GH + INS treatment increased ( P < 0.05) mean plasma concentration of INS (0.71 vs 0.96 ± 0.081 ng/mL), IGF-I (228.7 vs 392.3 ± 29.74 ng/mL), and glucose (48.1 vs 66.7 ± 2.12 mg/dL), decreased ( P < 0.01) plasma urea nitrogen (13.6 vs 10.4 ± 0.76 mg/dL), and did not affect GH (13.5 vs 12.7 ± 0.95 ng/mL). In the miniature Brahman model, both the GH and GH + INS treatments dramatically increased circulating concentrations of IGF-I in mature cattle, suggesting that this line of Brahman cattle is capable of responding to bioactive GH.

Evaluation of Final Height and Parentally Adjusted Height Deficit in Isolated Growth Hormone Deficient Children With or Without Short Parents

Abstract:Parental height is an important factor for predicting growth hormone (GH) effectiveness in children with GH deficiency (GHD). The aim of the study was to evaluate the effect of GH administration on final height in 2 groups of isolated GHD children, those with short parents or normal height

Effect of growth hormone on serum lipoproteins in growth hormone deficiency.

The effect of growth hormone treatment on the plasma lipoproteins was studied in 13 growth hormone deficient children. The pretreatment total cholesterol level was moderately (p less than 0.05) higher in growth hormone deficiency and it decreased significantly under the effect of growth hormone administration. This decrease was due to the reduction of HDL-cholesterol in the first week and to the decrease of LDL-cholesterol after one month of treatment. The level of LDL-cholesterol returned to normal at one month. The plasma triglyceride level increased significantly under the effect of growth hormone in the first week and returned to normal after one month. This change was due to the increase of VLDL-triglyceride level. There was no difference in the cholesterol and triglyceride concentrations of growth hormone deficient children with normal or subnormal plasma thyroxine concentrations.

No effect of growth hormone administration on substrate oxidation during exercise in young, lean men

The purpose of this study was to examine the effects of increased fat availability induced by growth hormone (GH) administration on the oxidative metabolism during exercise. Seven well-trained males (age 25 +/- 2 years (mean +/- S.E.M.); peak oxygen consumption : 62 +/- 1 ml min(-1) kg(-1) (completed four randomised trials: 120 min bicycling at 55% 4 h after receiving either 7.5 IU (2.5 mg) GH or placebo (Plc), and during rest after receiving either GH or Plc. In all studies a standardized meal was given 2 h after GH or Plc injection. GH administration resulted in an approximately 60-fold increase in serum GH concentration at rest (P < 0.0001) and during exercise (P < 0.0001). The increase in serum GH was followed by an increase in circulating glycerol at rest (8%, P < 0.0001). When combined with exercise the increase in plasma glycerol was more pronounced (GH: 716% of baseline versus Plc: 328%, P < 0.0001). However, this increase in fat mobilization did not increase fat oxidation during exercise (indirect calorimetry). In conclusion, GH administration combined with aerobic exercise increased lipolytic parameters substantially more than exercise alone, but did not further augment whole body fat oxidation.

Effect of Recombinant Human Growth Hormone on Age-Related Hepatocyte Changes in Old Male and Female Wistar Rats

Aging induces changes in several organs, such as the liver, and this process might be due to damage caused by free radicals and inflammatory mediators. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis shows a reduction with age, and this fact could be associated with some age-related changes. The aim of this study was to investigate the effect of GH administration on age-induced alterations in hepatocytes. Two and twenty two month-old male and female Wistar rats were used. Old rats were treated with human recombinant GH for 10 wk. At the end of the treatment, hepatocytes were isolated from the liver and cultured, and different parameters were measured in cells and medium. Plasma IGF-1 was also measured. Aging significantly decreased plasma IGF-1 in males. In females, plasma IGF-1 was also reduced, but not significantly. GH treatment restored plasma IGF-1 levels to values similar to young males. Aging was associated with a significant increase in lipid peroxidation (LPO), nitric oxide (NO), carbon monoxide (CO) and cyclic guanosyl-monophosphate (cGMP), as well as a reduction in adenosyl triphosphate (ATP) and phosphatidylcholine (PC) synthesis. GH administration partially prevented all these changes in males. In females, some of the parameters were significantly improved by GH (ATP, CO, cGMP), while others showed a tendency to improvement, although differences did not reach significance. In conclusion, GH administration could exert beneficial effects against age-related changes in hepatocytes, mainly in males.

On the mechanism of growth hormone-induced stimulation of renal acidification in humans: effect of dietary NaCl

Sustained administration of growth hormone (GH) to human subjects with NH4Cl-induced chronic metabolic acidosis (CMA) results in a large (4.5±0.5 mmol/l) increase in the plasma HCO3- concentration, as mediated by a large increase in renal net acid excretion. The renal mechanism(s) responsible for the potent stimulation of renal hydrogen ion secretion by GH remain to be elucidated. Accordingly, we have assessed the Na+ dependence of prolonged GH-stimulated renal acidification in four normal NaCl-restricted subjects (Na+ intake 0.3 mmol⋅kg-1⋅day-1) during CMA (4.2 mmol of NH4Cl⋅kg-1⋅day-1 for 7 days), CMA plus GH (0.1 unit/kg every 12 h for 5 days) and then CMA plus GH plus NaCl (1.7 mmol⋅kg-1⋅day-1 for 6 days). During CMA, urine Na+ excretion averaged 22.4±4.1 mmol/24 h. In response to GH administration, urinary net acid excretion was essentially unchanged, and the accumulated increment over 5 days of GH treatment was not different from zero (14±12 mmol; not significant). The plasma HCO3- concentration increased only slightly, from 14.2±0.8 to 15.0±1.1 mmol/l (P &lt; 0.05). Despite the constraint on net acid excretion imposed by NaCl restriction, renal ammonia production increased, as suggested by increases in urine pH from 5.58±0.05 to 5.82±0.04 (P &lt; 0.005) and unchanged NH4+ excretion (202±17 to 211±19 mmol/24 h; not significant). In response to dietary NaCl, urine pH decreased to 5.27±0.1 (P &lt; 0.001) and a large increment in net acid excretion accumulated (233±20 mmol; P &lt; 0.05), in association with an increase in plasma HCO3- to 18.7±1.3 mmol/l (P &lt; 0.001), a plasma HCO3- value similar to that reported previously in salt-replete, NH4Cl-fed subjects. These results demonstrate for the first time in any species that the acid excretory effect of GH administration is critically dependent on the availability of a surfeit of Na+ for tubular reabsorption. GH and/or insulin-like growth factor-1 affect renal acid excretion proximally (by stimulation of NH3 production) and by a Na+-transport-dependent mechanism in the collecting duct (voltage-driven acidification) in humans. The present results indicate that an isolated increase in renal NH3 production is insufficient to obligate an increase in net acid excretion.

On the mechanism of growth hormone-induced stimulation of renal acidification in humans: effect of dietary NaCl

Sustained administration of growth hormone (GH) to human subjects with NH(4)Cl-induced chronic metabolic acidosis (CMA) results in a large (4.5+/-0.5 mmol/l) increase in the plasma HCO(3-) concentration, as mediated by a large increase in renal net acid excretion. The renal mechanism(s) responsible for the potent stimulation of renal hydrogen ion secretion by GH remain to be elucidated. Accordingly, we have assessed the Na(+) dependence of prolonged GH-stimulated renal acidification in four normal NaCl-restricted subjects (Na(+) intake 0.3 mmol x kg(-1) x day(-1)) during CMA (4.2 mmol of NH(4)Cl x kg(-1) x day(-1) for 7 days), CMA plus GH (0.1 unit/kg every 12 h for 5 days) and then CMA plus GH plus NaCl (1.7 mmol x kg(-1) x day(-1) for 6 days). During CMA, urine Na(+) excretion averaged 22.4+/-4.1 mmol/24 h. In response to GH administration, urinary net acid excretion was essentially unchanged, and the accumulated increment over 5 days of GH treatment was not different from zero (14+/-12 mmol; not significant). The plasma HCO(3)(-) concentration increased only slightly, from 14.2+/-0.8 to 15.0+/-1.1 mmol/l (P<0.05). Despite the constraint on net acid excretion imposed by NaCl restriction, renal ammonia production increased, as suggested by increases in urine pH from 5.58+/-0.05 to 5.82+/-0.04 (P<0.005) and unchanged NH(4)(+) excretion (202+/-17 to 211+/-19 mmol/24 h; not significant). In response to dietary NaCl, urine pH decreased to 5.27+/-0.1 (P<0.001) and a large increment in net acid excretion accumulated (233+/-20 mmol; P<0.05), in association with an increase in plasma HCO(3-) to 18.7+/-1.3 mmol/l (P<0.001), a plasma HCO(3-) value similar to that reported previously in salt-replete, NH(4)Cl- fed subjects. These results demonstrate for the first time in any species that the acid excretory effect of GH administration is critically dependent on the availability of a surfeit of Na(+) for tubular reabsorption. GH and/or insulin-like growth factor-1 affect renal acid excretion proximally (by stimulation of NH(3) production) and by a Na(+)-transport-dependent mechanism in the collecting duct (voltage-driven acidification) in humans. The present results indicate that an isolated increase in renal NH(3) production is insufficient to obligate an increase in net acid excretion.

Effect of growth hormone administration on IGF binding protein-3 mRNA levels in porcine tissues.

The effect of short-term GH treatment on steady-state insulin-like growth factor binding protein-3 (IGFBP-3) mRNA levels in liver, kidney, longissimus dorsi muscle, stomach and jejunum was examined in pigs. Ten female crossbred pigs were allocated to either saline or GH (70 microg/kg/day) treatment by subcutaneous injection for 4 days. They were allowed to feed ad libitum, and were weighed daily. At the end of the treatment period, the pigs were slaughtered and samples of liver, kidney, skeletal muscle, stomach and jejunum were collected and total RNA was extracted. Steady-state levels of IGFBP-3 mRNA were quantified by RNase protection assay and were compared with the level of IGF-I class 1 and class 2 transcripts. IGFBP-3 mRNA increased in response to GH in both liver and kidney, but not in the other tissues sampled. Hepatic IGF-I mRNA responded to short-term GH treatment with a fourfold increase in IGF-I class 1 mRNA and an eightfold increase in IGF-I class 2 mRNA, which was liver specific. IGF-I class 1 mRNA was not responsive to GH treatment in other tissues. The short-term nature of this treatment suggests that the increase in hepatic IGFBP-3 and IGF-I transcripts is a relatively early response to treatment with GH, and that the increase in plasma concentrations of IGFBP-3 in response to GH are derived from the liver, the kidney, or both.

Growth hormone treatment of short children born small for gestational age: metanalysis of four independent, randomized, controlled, multicentre studies

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. The effect of GH administration was evaluated over 2 years in short prepubertal children born SGA. The children (n = 244), who were taking part in four independent multicentre studies, had been randomly allocated to groups receiving either no treatment or GH treatment at a daily dose of 0.1, 0.2 or 0.3 IU/kg (0.033, 0.067 or 0.1 mg/kg) s.c. At birth, their mean length SD score (SDS) was -3.6 and their mean weight SDS -2.6; at the start of the study, mean age was 5.2 years, bone age 3.8 years, height SDS -3.3, height SDS adjusted for parental height -2.4, weight SDS -4.7 and body mass index (BMI) SDS -1.4. The untreated children had a low-normal growth velocity and poor weight gain. Although bone maturation progressed more slowly than chronological age, final height prognosis tended to decrease, according to height SDS for bone age, GH treatment induced a dose-dependent effect on growth, up to a near doubling of height velocity and weight gain; BMI SDS was not altered. Bone maturation was also accelerated differentially; however, final height prognosis increased in all GH treatment groups. The more pronounced growth responses were observed in younger children with a lower height and weight SDS. In conclusion, GH administration is a promising therapy for normalizing short stature and low weight after insufficient catch-up growth in children born SGA. Long-term strategies incorporating GH therapy now remain to be established.

Growth hormone normalizes low-density lipoprotein receptor gene expression in hypothyroid rats

Hypothyroidism leads to a decreased activity of the low-density lipoprotein (LDL) receptor, which contributes to the hypercholesterolemia frequently seen during hypothyroidism. It is not known whether the decreased activity of the LDL receptor is directly due to the absence of thyroid hormone, or secondary to a deficiency of growth hormone (GH). Therefore, the effect of GH administration on LDL receptor activity was studied in hypothyroid rats. Following induction of hypothyroidism, the level of LDL receptor mRNA was significantly decreased in liver homogenates to 31% ± 6% of the control value. LDL binding to liver cell membranes and plasma membranes decreased during hypothyroidism to approximately 65% of the control value. The effect of hypothyroidism on the hepatic LDL receptor was reflected in a significantly increased half-life of 125I-LDL of 29 hours in controls versus 48 hours in hypothyroid rats. Treatment of hypothyroid rats with human GH (hGH) resulted in normalization of both the amount of hepatic LDL receptor mRNA and LDL binding on liver cell membranes. The plasma half-life of human 125I-labeled LDL decreased during GH substitution but did not normalize. GH treatment significantly reduced plasma LDL cholesterol levels by 36% ( P < .05, n = 8), to levels that were still higher than in control animals. These data indicate that at least part of the decreased LDL receptor activity during hypothyroidism is secondary to GH deficiency.

Effect of Growth Hormone Administration on Thymus Size, Peripheral T Lymphocyte and T Lymphocyte Subsets in Growth Hormone Deficiency

Experimental evidence suggests that growth hormone (GH) has an important role in the development of T lymphocytes within the thymus. In this study, we investigated the effect of 3-month therapy with GH on the peripheral T lymphocytes, T lymphocyte subsets and thymus size with magnetic resonance imaging measurement of GH-deficient children. We found that GH-deficient chlidren had smaller thymi when compared with healthy age-matched children, but their peripheral T lymphocytes and T lymphocte subsets were within normal range. There were no change in the total peripheral T lymphocytes and T lymphocte subtsets, but thymus size significantly increased wtih GH administration. These findings suggest that GH acts as a thymopoietic agent wtithout any effect on the number of peripheral T lymhocytes.

Effect of fasting and growth hormone (GH) administration on gh receptor (GHR) messenger ribonucleic acid (mRNA) and GH-binding protein (GHBP) mRNA levels in male rats

To elucidate whether GHR and GHBP are coordinately regulated or not, we studied the effect of fasting with or without GH administration on the GHR and GHBP mRNAs in the liver as well as in extrahepatic tissues in rats. Tissues were collected from 7-week-old male rats by decapitation 1, 3, and 7 days after the start of fasting. Liver GHR mRNA levels were not affected 1 day after the start of fasting but progressively decreased for the subsequent 3 and 7 days of fasting as compared with those in control rats fed ad libitum. In contrast, liver GHBP mRNA levels significantly rose after 1 day fasting, returned to the control level after 3 days and further reduced after 7 days of fasting. Changes in GHBP mRNA level after fasting were different among the tissues. A transient increase in GHBP mRNA levels was observed in muscle and heart as well as liver, while the GHBP mRNA levels in fat tissues did not change throughout 7 days of fasting. Next, bovine GH(bGH) was administered ip to the fasted rats and control fed rats for either 1 day(100mg, tid) or 5 days(150mg, daily). In fed rats, liver GHR mRNA level was significantly increased by 1 day bGH treatment, but after 5 days treatment with bGH it was not different from the level in saline-injected control. Accordingly, net increment of plasma IGF-I was 296.0 ng/ml with 1 day bGH treatment and 234.2 rig/ml with bGH administration for 5 days. In fasted rats, liver GHR mRNA level did not changed after 1 day treatment with bGH, but markedly decreased 5 days after bGH administration. Net increment of plasma IGF-I was slightly reduced to 284 ng/ml with 1 day treatment with bGH, and markedly decreased to 37.0 with bGH administration for 5 days. The effect of GH administration on liver GHBP mRNA level was virtually absent in either fasting or fed state. These findings suggest that GHR and GHBP mRNAs in the liver are expressed in different ways and that expression of GHBP mRNA is differently regulated among tissues.