Daily Growth Hormone Injections Research Articles

Differential effects of growth hormone and prednisolone on energy metabolism and leptin levels in humans

Short-term growth hormone (GH) exposure has been shown to stimulate energy expenditure (EE) without concomitant changes in body composition. To what extent this is related to thyroid function, sympathetic activity, hyperinsulinemia, or leptin secretion is unknown. It is also unknown whether the calorigenic effect of GH is influenced by glucocorticoids, which are known to antagonise the anabolic actions of GH. To pursue this, eight normal male subjects (aged 22 to 28 years; body mass index, 21.6 to 26.3 kg/m 2) were randomly studied during four 4-day treatment periods with (1) day subcutaneous (SC) placebo injections and placebo tablets, (2) daily SC GH injections (0.1 IU/kg · d) and placebo tables, (3) daily prednisolone administration (25 mg morning and evening) plus placebo injections, and (4) daily GH injections plus prednisolone administration. GH administration decreased plasma epinephrine significantly (mean ± SE, 34.7 ± 5.7 ng/L for control v 24.8 ± 5.8 for GH, P < .05), had no effect on plasma norepinephrine or serum leptin, and increased both free triiodothyronine (FT 3) levels (5.7 ± 0.3 pmol/L for control v 6.7 ± 0.3 for GH, P < .05) and resting EE ([REE] 1,861 ± 61 kcal/24 h for control v 1,996 ± 69 for GH, P < .05). Prednisolone administration did not affect epinephrine and REE, decreased norepinephrine (116 ± 13, P < .05) and FT 3 (4.7 ± 0.2, P < .05), and increased leptin (3.93 ± 0.71, P < .05). Concomitant GH and prednisolone administration increased REE (2.068 ± 85, P ± .05) and leptin (4.82 ± 0.93 P ± .05), had no effect on either epinephrine or norepinephrine, and decreased FT 3 (5.0 ± 85, P ± .05). Resting heart rate (HR) increased only during GH, whereas sympathetic nerve activity was unchanged in all studies. Our data suggest that (1) the calorigenic effect of GH is not mediated by changes in sympathetic activity or leptin secretion, (2) rapid elevations in leptin induced by glucocorticoids do not affect EE in humans, and (3) the acute calorigenic effects of GH are probably related to increased cardiac workload.

SEX-SPECIFIC EFFECTS OF GROWTH HORMONE ON HEPATIC 11 β-HYDROXYSTEROID DEHYDROGENASE ACTIVITY AND GENE EXPRESSION IN HYPOTHYROID RATS

To investigate the effects of growth hormone (GH) on 11 β-HSD 1, we determined changes in hepatic 11 β-HSD 1 activity in hypothyroid rats following treatment with subcutaneous (s.c) injection of GH for periods ranging from 24 h to 7 days. In male rats, hypothyroidism markedly reduced the hepatic 11 β-HSD 1 activity and serum testosterone levels (p < 0.01). Subcutaneous injection of GH once daily to male hypothyroid rats for 48 h inhibited hepatic 11 β-HSD 1 activity. However, the same daily dose of GH administered to male hypothyroid rats for 7 days, resulted in a marked increase in hepatic 11 β-HSD 1 activity and gene expression (p < 0.01). Furthermore, daily s.c injections of GH to castrated male hypothyroid rats for 7 days reduced hepatic 11 β-HSD 1 activity rather than inducing it, the same response seen in hypothyroid female rats. In addition, the treatment of castrated male hypothyroid rats with testosterone for 7 days significantly increased this enzyme activity (p < 0.01). The changes in hepatic 11 β-HSD 1 were demonstrated to be associated with the testes in hypothyroid male rats following treatment with GH for 7 days. Moreover, the prolonged exposure to GH required to induce hepatic 11 β-HSD 1 in intact hypothyroid male rats and the lack of a similar effect in castrated male hypothyroid rats suggests that this action is indirect and that it may be mediated by androgen production from Leydig cells of the testes and induced by the daily injections of GH. Treatment of hypothyroid male rats with GH at 6-h intervals, however, feminized the hepatic 11 β-HSD 1 gene expression.

Effects of growth hormone on serum lipids and lipoproteins: Possible significance of increased peripheral conversion of thyroxine to triiodothyronine

The role of growth hormone (GH) and thyroid hormone in the regulation of lipid and lipoprotein metabolism is not fully established. Furthermore, the possible linkage between the well-known GH-induced increase in peripheral thyroxine (T 4) to triiodothyronine (T 3) generation and the effects of GH on lipid and lipoprotein metabolism has not been elucidated. In this double-blind placebo-controlled study, we compared the effects of GH and T 3 administration alone and in combination on lipid and lipoprotein metabolism in a group of healthy young adults. The dose of T 3 was selected to mimic the T 3 increase seen during exogenous GH exposure. Eight normal male subjects (aged 21 to 27 years; body mass index, 21.11 to 27.17 kg/m 2) were randomly studied during four 10-day treatment periods with (1) daily subcutaneous placebo injections and placebo injections and placebo tablets, (2) daily subcutaneous GH injections (0.1 IU/kg · d) and placebo tablets, (3) daily T 3 administration (40 μg on even dates or 20 μg on uneven dates) plus placebo injections, and (4) daily GH injections plus T 3 administration. GH administration increased free T 3 (FT 3) to the same level as during T 3 administration. GH caused decreased levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol and increased levels of triglycerides (TG) and lipoprotein(a) (Lp(a)), but no changes in high-density lipoprotein (HDL) cholesterol and apolipoprotein B (apo B). T 3 administration caused no alteration in these parameters, except for decreased levels of TC comparable to those seen after GH administration. Combined GH and T 3 administration caused changes identical to those seen after GH administration, in addition to decreased apo B levels and a further decrease of TC levels. We conclude that GH and iodothyronines in the physiologic range exert distinct but disparate effects on lipids and lipoproteins, and do not support the hypothesis that the effects observed during GH administration are exclusively secondary to changes in peripheral T 3 levels.

Increased serum lipoprotein(a) concentrations after growth hormone (GH) treatment in patients with isolated GH deficiency.

Fourteen post-pubertal subjects (11 male, 3 female) with isolated growth hormone (GH) deficiency were treated with a low dose (0.125 U/kg for the first 4 weeks and thereafter 0.25 U/kg/week) daily sc GH injection for 1 year. Fasting blood samples were collected at entry into the study and subsequently at 3 monthly intervals for estimation of serum cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and lipoprotein(a) [Lp(a)]. Serum Lp(a) increased progressively during the treatment period (by analysis of variance) and was 41% higher at 12 months (P < 0.02) despite the fact that five patients showed little or no change. There was no significant change in any of the other lipid fractions. These observations are of concern as Lp(a) is an independent risk factor for cardiovascular disease and should introduce a cautionary note into the enthusiastic efforts to offer GH replacement to all GH deficient adults.

Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults. II. Effects on serum lipoproteins and lipoprotein and hepatic lipase activity

Recombinant human growth hormone (GH) administered as daily subcutaneous (SC) injections has been shown to affect serum lipoproteins in GH-deficient subjects. However, the effects of continuous infusion of GH on serum lipoproteins have not been investigated in GH-deficient adults. The aim of the present study was to compare effects of daily injections and continuous infusion of GH on lipoprotein metabolism. Recombinant human GH (0.25 U/kg/wk) was administered to nine GH-deficient adult men during a period of 14 days in two different ways, ie, as a daily SC injection at 8:00 pm and as a continuous SC infusion, with 1 month of washout between the treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatment (day 0) and on day 2 and day 14 of treatment. Abdominal SC adipose tissue lipoprotein lipase (LPL), postheparin plasma LPL, and hepatic lipase (HL) activity were measured 120 minutes after the intake of 100 g glucose. Adipose tissue LPL activity decreased and postheparin plasma HL activity increased after 14 days of GH treatment irrespective of the mode of GH administration, whreas GH treatment had no effect on postheparin plasma LPL activity. Serum triglyceride and very-low-density lipoprotein (VLDL) triglyceride concentrations increased during GH treatment. However, VLDL triglyceride concentrations increased to a greater degree during treatment with daily GH injections than during continuous infusion of GH. Serum apolipoprotein (apo) B and low-density lipoprotein (LDL) cholesterol concentrations decreased during treatment with daily GH injections, but were not significantly affected by continuous GH infusion. Thus, apo B and LDL cholesterol concentrations were lower after daily GH injections versus continuous GH infusion. Serum lipoprotein(a) [Lp(a)] and apo E concentrations increased during both modes of GH treatment. However, continuous infusion of GH resulted in a more marked increase in Lp(a) and apo E concentrations than daily GH injections. Minor effects were observed on serum apo A-I concentrations, but high-density lipoprotein (HDL) cholesterol concentrations were not affected. In conclusion, GH treatment of GH-deficient men influenced adipose tissue LPL and postheparin plasma HL activity, as well as serum lipoprotein concentrations. Moreover, continuous GH infusion and daily GH injections differed with respect to the magnitude of effects on several lipoprotein fractions including VLDL triglycerides, LDL cholesterol, apo B, apo E, and Lp(a) concentrations.

Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults: 1. effects on insulin-like growth factor-I (IGF-I), GH and IGF binding proteins, and glucose homeostasis

Recombinant human growth hormone (GH) is routinely administered as daily subcutaneous injections to patients with GH deficiency (GHD). However, in the hypophysectomized rat, pulsatile and continuous infusion of GH has been shown to differ in terms of the magnitude of effect on longitudinal bone growth, serum insulin-like growth factor-I (IGF-I) concentrations, and hepatic metabolism. The aim of the present study was to compare the effects of daily injections and continuous infusion of GH in GHD adults on previously well-documented GH-dependent factors. Recombinant human GH (0.25 U/kg/wk) was administered to nine men with GHD for 14 days in two different ways, ie, as a daily subcutaneous injection at 8 pm and as a continuous subcutaneous infusion, with 1 month of washout between treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatment (day 0) and on day 2 and day 14 of treatment. An oral glucose tolerance test (OGTT) was performed on day 0 and day 14. Daily injections and continuous infusion of GH exerted similar effects in terms of body weight and body composition. The two modes of administration resulted in similar daily urinary GH excretion and similar serum GH concentrations in the morning. GH binding protein (GHBP) concentrations did not change significantly during the various treatment periods. Serum IGF-I and IGF-I binding protein (IGFBP)-3 concentrations increased to a greater degree during continuous infusion of GH versus daily injections. Serum IGFBP-1 concentrations decreased to a similar degree during the two modes of administration. Serum concentrations of free triiodothyronine and total triiodothyronine (T 3) increased and free thyroxine (T 4) decreased to a similar degree, independent of the mode of administration. However, total T 4 concentrations were unchanged during both modes of treatment. Serum thyrotropin (TSH) concentrations decreased during continuous infusion, and there was a similar nonsignificant decrease during daily injections of GH. Fasting free fatty acid (FFA) levels increased during treatment with one daily injection of GH, but there was no significant effect from continuous infusion. Results of measurements of fasting concentrations of blood glucose and oral glucose tolerance (OGT) indicated a more impaired glucose tolerance after daily injections of GH versus continuous infusion. In conclusion, continuous infusion and daily injections of GH have similar effects on the variables described, but the magnitude of the effects differs.

Continuous infusion versus daily injections of growth hormone (GH) for 4 weeks in GH-deficient patients.

Endogenous GH secretion is pulsatile. Animal studies indicate that GH administered in a pulsatile manner induces growth and insulin-like growth factor I (IGF-I) generation more effectively than continuous administration. Short term human studies, however, have reported similar metabolic effects with constant and pulsatile GH delivery. This study was carried out to compare the metabolic effects of longer term continuous infusion vs. daily injections of GH. Thirteen GH-deficient patients were studied in a cross-over design. The patients were randomized to receive GH as a continuous sc infusion by means of a portable pump for 1 month and as daily sc injections (at 1900 h) for another month. An average daily GH dosage (+/- SEM) of 3.15 +/- 0.27 IU was administered during both periods. Steady state 24-h profiles of GH, IGF-I, IGF-binding proteins (IGFBPs), insulin, glucose, lipid intermediates, and other metabolites were monitored after each treatment period. At the end of each study period (at 0800 h), an oral glucose tolerance test was performed. The mean (+/- SEM) integrated levels of serum GH (micrograms per L) were higher after GH injection [2.51 +/- 0.54 (injection) vs. 1.77 +/- 0.35 (infusion); P < 0.02]. Continuous infusion induced higher nighttime than daytime GH levels (P = 0.01), indicating a diurnal variation in the absorption or clearance of GH. Serum IGF-I levels (micrograms per L) were slightly higher (P < 0.05, by analysis of variance) after continuous GH infusion [312.5 +/- 50.2 (injection) and 334.6 +/- 46.6 (infusion)]. Similarly, constant GH delivery induced higher IGFBP-3 levels (P < 0.05, by analysis of variance). Serum IGFBP-1 levels were similar on the two occasions. Daily GH injections increased daytime insulin levels (P < 0.05), whereas 24-h levels were similar (P = 0.14). The trend toward increased insulin levels after GH injections was also found during the oral glucose tolerance test (P = 0.07). Blood glucose levels were identical on the two occasions. Nocturnal levels of nonesterified fatty acids were higher (P < 0.05) after GH injection. We conclude that continuous sc infusion of GH induced serum IGF-I and IGFBP-3 levels more effectively than daily sc injections. The constant appearance of GH in the circulation did not impair glucose tolerance, but resulted in a less physiological diurnal pattern of nonesterified fatty acids. Our data do not support the concept that a pulsatile GH pattern is of critical physiological significance.

Continuous infusion versus daily injections of growth hormone (GH) for 4 weeks in GH-deficient patients

Continuous infusion versus daily injections of growth hormone (GH) for 4 weeks in GH-deficient patients

Timed Daily Administrations of Hormones and Antagonists of Neuroendocrine Receptors Alter Day-Night Rhythms of Allograft Rejection in the Gulf Killifish, Fundulus Grandis1

Immune activity during scale allograft rejection, measured by melanophore destruction, is two to three times greater at night (12-hr scotophases) than during the day (12-hr photophases) in gulf killifish (Fundulus grandis). In the present study of killifish, hormones and antagonists of neuroendocrine receptors were administered daily at 0800 or 2000 hr during either 12-hr photoperiods (light onset: 0800 hr) or continuous light to examine possible neuroendocrine regulation of the allograft rejection rhythm. Immune activity peaked 0-12 hr after the time of daily growth hormone injections (0800 or 2000 hr) in fish held under continuous light and examined twice daily (0800 and 2000 hr) for melanophore breakdown. Immune activity peaked 12-24 hr after the time of day when cortisol-supplemented meals were provided (light onset or light offset) whether fish were treated throughout the days of melanophore examinations or pretreated for 3 days only prior to melanophore examinations. Daily rhythms of immune activity were not observed in fish treated with propranolol or naloxone at light offset only, growth hormone or atropine at light onset only, or prolactin at either light onset or light offset; these timed-treatments also reduced (prolactin or growth hormone) or prolonged (propranolol or naloxone) the length of time needed to destroy all melanophores within an allograft compared with controls. These results demonstrate that neuroendocrine factors can modulate a daily rhythm of immune function in fish.

Final height and pubertal development in children with growth hormone deficiency after long-term treatment.

Auxological data and final height were analysed in 42 patients with growth hormone deficiency (GHD), 10 had isolated GHD (group 1), 23 had multiple pituitary hormone deficiencies (group 2) and 9 had organic GHD (group 3). Patients received growth hormone (GH) for a mean of 6.5 +/- 2.6 (group 1), 8.0 +/- 2.9 (group 2) and 2.9 +/- 1.5 years (group 3). Most patients were treated with pituitary GH (pGH), 11 IU/m2/week (mean) in 3 divided doses, which was not changed during puberty. Six patients, treated with daily injections of recombinant GH, showed a significantly better height velocity than those treated with pGH (2.1 vs. -0.3 SDS), though the mean dose was identical (p = 0.03). Final heights for boys and girls were -2.8 and -3.3 SDS (group 1), -1.9 and -1.6 SDS (group 2), and -2.9 and -3.2 SDS (group 3). Only 20% of group 1, 70% of group 2 and 22% of group 3 reached final heights within target limits. Final height was positively correlated with height at onset of puberty, but there was no association with the timing or magnitude of pubertal growth.

No effect of growth hormone on bone graft incorporation. Titanium chamber study in the normal rat.

A recent series of publications reported greatly improved mechanical properties and increased callus size during the late stages of fracture healing in normal (not hypophysectomized) rats after twice daily injections of growth hormone (GH). We tested whether GH could enhance the incorporation of bone allografts in a new experimental model where we have demonstrated an increase in bone allograft incorporation by local application of basic fibroblast growth factor (bFGF). Cylinders of defatted allogeneic cancellous bone were placed as grafts in titanium Bone Conduction Chambers in the tibiae of female rats. Only one end of this chamber is open for tissue ingrowth. This permits us to measure the distance into the graft that new bone penetrates after entering the chamber. We injected 10 rats with 1.5 IU per rat of subcutaneous human recombinant GH twice daily for 6 weeks and another 10 rats with similar doses of sterile normal saline. GH caused a constant increase in the rate of weight gain and in the serum concentration of insulin-like Growth Factor 1 (IGF 1). Tibiae became longer and the ash weight of the second tail vertebra was increased. We also noted an increased joint cartilage thickness. There was no difference in the amount of new bone that had penetrated and replaced parts of the graft in GH-treated or control rats and this was also the case with TcMDP activity of bone samples from both groups. New bone forms in the grafts by membranous (metaplastic) ossification. It appears that the effects of excessive GH stimulation on endochondral and membranous ossification in this model are markedly different.

Effect of growth hormone deficiency on hormonal control of hepatic glycogenolysis in hypophysectomized rat

The present study was designed to investigate the hormonal regulation of rat liver glycogenolysis in growth hormone (GH) deficiency. To this end, hepatocytes were isolated from control, GH-deprived (hypophysectomized and treated with triiodothyronine [T 3] and corticotropin), and 7-day GH-supplemented fed rats and incubated with glucagon and α 1-adrenergic agonist (phenylephrine) to measure the hormonal activation of both glycogen phosphorylase and glucose production from glycogen stores. GH deficiency induces a combined decrease of 50% of the glycogen content, the activity of glucose-6-phosphatase, and the maximal hormone-induced glycogen phosphorylase activity. Daily GH injections restore the levels of both glycogen phosphorylase and glucose-6-phosphatase. These enzymatic inductions occur without normalization of insulinemia. Despite the reduced levels of key enzymes of glycogenolysis, the stimulation of glucose production from glycogen in response to glucagon and phenylephrine is not modified in GH-deprived rats. An increase in the intrinsic activity of one or both of the enzymatic steps is postulated to compensate for the lower levels of enzymes, as indicated by the slopes of the correlation between glucose production and phosphorylase a activity (107 and 216 nmol glucose produced/min/U phosphorylase a [ P < .001] in control and GH-deprived rats, respectively). GH replacement enhances maximal phosphorylase activity and brings the correlation toward the control value (slope, 128 nmol glucose produced/min/U phosphorylase a). Our findings demonstrate that glycogenolysis in hepatocytes isolated from GH-deprived rats is normal, despite a reduction of glycogen phosphorylase and glucose-6-phosphatase activities. These results suggest the existence of some adaptative mechanisms that increase the specific activity of one of the enzymes to produce an equal amount of glucose in the presence of fewer enzymatic proteins.

In vivo effects of growth hormone on thymus function in aging mice

It is well demonstrated that the normal functioning of the thymus gland is under neuroendocrine control. Thus, steroid, thyroid, and pituitary hormones can affect distinct structural and/or functional thymic parameters. Particularly growth hormone (GH) was shown to be capable of restoring some thymus functions in old individuals. This prompted us to carry out a multiparametric analysis of the thymus in young, middleaged, and old mice, subjected to GH treatment lasting 3 or 6 weeks. For that, we treated animals with daily injections of ovine GH (2 μg/g BW). Although the general microarchitecture of the thymus remained unchanged following in vivo GH treatment, there was a clearcut increase in thymulin production, independent of the age group analyzed. Regarding the lymphoid compartment, we could not find evidence of changes in total thymocyte numbers nor in the subsets phenotypically defined by the expression of CD3, CD4, and CD8 antigens. Nonetheless, in GH-treated middle-aged and old mice, the concanavalin A-dependent proliferative response of thymocytes, as well as IL-6 production were enhanced compared to age-matched controls. These findings support the notion that GH has a pleiotropic effect upon the thymus, functionally affecting both microenvironmental and lymphoid compartments of the organ.

Effect of growth hormone therapy on IGF-I, bone GLA-protein and bone mineral content in short children with and without chronic renal failure.

Chronic renal failure (CRF) in the young is complicated by, among other conditions, growth retardation, hyperparathyroidism and uremic osteodystrophy. Many children with CRF are now being treated with growth hormone (GH). Since GH has a direct mitogenic effect on osteoblasts in culture, we studied the effects of GH therapy on osteoblastic activity, such as serum alkaline phosphatase (AP), bone GLA-protein (BGP) and bone mass density (BMD) in poorly growing children with and without CRF. Fifteen (4 girls, 11 boys) healthy children with short stature (SS) and 10 (3 girls, 7 boys) children with end-stage renal failure (CRF) 4.5-12.4 years of age were treated with daily subcutaneous injections of GH in a dose of 0.1-0.125 IU/kg/day for 1 year. IGF-I, BGP and BMD of the spine were determined before and after the year of treatment. During GH therapy, a similar increase in height velocity and IGF-I were noted in SS and CRF groups: 3.8 +/- 0.77 to 8.38 +/- 1.25 (p < 0.001) vs. 4.0 +/- 0.6 to 7.14 +/- 1.3 cm/year (p < 0.001) and 7.8 +/- 2.6 to 21.8 +/- 7.5 (p < 0.01) vs. 7.9 +/- 1.3 to 21.5 +/- 5.6 nmol/l (p < 0.01), respectively. AP increased from 205 +/- 27 to 274 +/- 50 IU/l (p < 0.01) in the SS group but not in CRF patients (223 +/- 58 pre- 218 +/- 51 IU/l post-GH therapy).(ABSTRACT TRUNCATED AT 250 WORDS)

Action and interaction of growth hormone and the β-agonist, clenbuterol, on growth, body composition and protein turnover in dwarf mice

The responses of dwarf mice to dietary administration of clenbuterol (3 mg/kg diet), daily injections of growth hormone (15 micrograms/mouse per d) or both treatments combined were investigated and their actions, and any interactions, on whole-body growth, composition and protein metabolism, and muscle, liver and heart growth and protein metabolism, were studied at days 0, 4 and 8 of treatment. Growth hormone, with or without clenbuterol, induced an increase in body-weight growth and tail length growth; clenbuterol alone did not affect body-weight or tail length. Both growth hormone and clenbuterol reduced the percentage of whole-body fat and increased the protein:fat ratio. They also increased protein synthesis rates of whole body and muscle, although the magnitude of the increase was greater in response to growth hormone than to clenbuterol. Clenbuterol specifically induced growth of muscle, with a decrease in liver protein content, whereas growth hormone exhibited more general anabolic effects on tissue protein. Previous reports have suggested that effects of clenbuterol on skeletal muscle are mediated, at least in part, via decreased rates of protein degradation; we could find little evidence of any decrease in whole-body or tissue protein degradation and anabolic effects were largely due to increases in protein synthesis rates. However, small increases in muscle protein degradation rate were observed in response to growth hormone. Growth hormone induced a progressive increase in serum insulin-like growth factor-1 concentration, whereas there was no change with clenbuterol administration. Anabolic effects on whole-body and skeletal muscle protein metabolism, therefore, appear to be initially via independent mechanisms but are finally mediated by a common response (increased protein synthesis) in dwarf mice.

Growth Hormone Response to a Bolus Injection of 1-44 Growth-Hormone-Releasing Hormone in Very Short Children with Intrauterine Onset of Growth Failure

The release of growth hormone (GH) during the 120 min following a bolus venous injection of 1-44 GH-releasing hormone (GHRH) 2 micrograms/kg was studied in 52 prepubertal children aged 8.4 +/- 2.1 years, having a nonfamilial growth deficiency of prenatal onset (-3.26 +/- 1.13 SDS at birth, -3.22 +/- 0.88 SDS at the time of study) and a normal response to conventional GH stimulation tests. GH release reached a peak level of 96.1 +/- 60.2 microU/ml, being significantly higher than that found in 68 non-GH-deficient very short children whose growth failure had a postnatal onset, and not significantly correlated with the response to conventional tests. 26 of the 52 intrauterine growth retardation (IUGR) patients were re-tested with GHRH in similar conditions after 6-12 months of daily subcutaneous injections of GH and 2 days without. They reached at the second test a peak plasma GH level of 91.7 +/- 56.1 microU/ml, not different from their response to the first test. These data could be taken into consideration for long-term studies of the clinical effects of GH in IUGR children with persisting severe growth deficiency.

Frequency of Administration of Growth Hormone &amp;ndash; An Important Factor in Determining Growth Response to Exogenous Growth Hormone

Growth hormone (GH) secretion in man occurs in a pulsatile manner with a dominant periodicity of 200 min. Animal studies and growth hormone-releasing hormone therapeutic studies in man demonstrate the importance of the frequency of GH pulses on the growth response observed. Daily injections of GH produce effective growth. More frequent regimens may be beneficial to prevent waining of the growth spurt induced by GH therapy.

The effects of bovine growth hormone and thyroxine on growth rate and carcass measurements in lambs.

The effects of bovine growth hormone (GH) and thyroxine (T4) on growth and carcass characteristics were assessed in Dorset ram lambs. Lambs in four groups (n = 10/group) were treated for 30 d as follows: controls, 3.33 mg (6 IU) GH/d (s.c.); 5-mg T4 implant (s.c.) on d 1 and a 10-mg T4 implant 21 d later; GH + T4. Blood samples were collected at 3-d intervals for analysis of GH, T4, triiodothyronine, somatomedin-C and testosterone concentrations. Six lambs/group were slaughtered for carcass measurements and composition. Daily GH injections increased (P less than .005) baseline plasma GH levels 10-fold, whereas plasma T4 concentrations were increased 10% (P less than .10) by the implants. Somatomedin-C increased with time in all groups, but the increments from d 0 to d 30 were higher (P less than .05) with GH treatment. Average daily gain (mean = 352 g/d), feed consumption and feed to gain ratio were not affected (P greater than .1) by GH or T4 treatment in ram lambs. Hot carcass weight and dressing percentage were increased (P less than .05) by T4. Growth hormone increased carcass protein content (P less than .005) and muscle weights while reducing carcass fat (P less than .05). Carcass composition was not altered by T4 alone, and the T4 x GH interaction was not significant; however, the combination of T4 and GH resulted in greater muscle and protein weight than did either hormone alone or no hormone administration. There were no differences in bone length or in the metacarpal growth plate width among groups. The beneficial effects of GH on carcass composition were not further enhanced by administration of thyroxine.

THE INFLUENCE OF EXOGENOUS GROWTH HORMONE ON OVULATION RATE IN GILTS

A total of 32 prepubertal gilts of Yorkshire and Landrace breeding were selected at 138 d and fed ad libitum a 16.2% crude protein diet formulated to provide 13.1 MJ DE kg−1. From selection until the end of second estrus, the gilts were exposed to a boar for 30 min d−1 to facilitate the detection of pubertal and second estrous periods. From 14 d after puberty, the gilts received daily injections of either porcine growth hormone at 90 μg kg−1 body weight (GH; n = 20) or vehicle (CT; n = 12) until 24 h after the onset of second estrus and were then killed 9 d later to determine ovulation rate. Gilts not displaying a second estrus by 24 day after puberty were considered anestrus and the injection regime was halted. Anestrous gilts were killed 30–32 d after puberty and their ovaries examined for the presence of corpora albicantia and the absence of corpora lutea. Blood samples were obtained from all gilts at 14, 17, and 20 d after puberty. There was no treatment effect on the duration of the estrous cycle (20.8 vs. 21.3 d for GH and CT, respectively), but while all CT gilts cycled normally, only 55% of the GH gilts had a second estrus (P &lt; 0.01). In those gilts having a second estrus, the daily injection of growth hormone increased ovulation rate (14.3 vs. 12.4 for GH and CT respectively; P &lt; 0.03). Serum type 1 insulin-like growth factor (IGF-1) concentrations were higher (P &lt; 0.001) in GH than in CT gilts, but there was no difference between cycling and anestrous GH gilts. We suggest that the effect of growth hormone on ovulation rate was mediated by increased secretion of IGF-1. The etiology of the high incidence of anestrus is, however, not known. Key words: Gilts, growth hormone, ovulation rate

Growth response to daily subcutaneous administration of growth hormone.

AbstractThe effect on growth rate of daily subcutaneous (sc) administration of growth hormone (GH) was studied in seven GH‐deficient children. All patients had been receiving conventional GH treatment (intramuscularly, twice or thrice weekly) for three to six years. The growth‐promoting effect of conventional treatment gradually decreased in these seven patients [4.0 ± 0.3 (mean ± SD) cm%sol;year during the last preceding year of conventional treatment]. Following transfer to daily sc GH treatment without increase in weekly dosage, all seven patients showed an increase in growth rate (7.5 ±1.1 cm%sol;year, P&gt;0.001). During the period of daily sc GH treatment, the pubertal stage did not advance in six of the seven patients. An increase in Δheight age%sol;Δbone age ratio was observed in six patients. None of the patients developed antibodies against GH. Local reactions were not observed at the injection site. Daily sc GH injections were tolerated without complaint. In conclusion, daily sc GH treatment is recommended for patients whose growth response to conventional GH treatment is poor.