Serum Growth Hormone Concentrations Research Articles

Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene.

Isolated growth hormone (GH) deficiency (IGHD) is a rare cause of short stature. The same mutation of the gene encoding the growth hormone-releasing hormone receptor (GHRHR) has been identified as the basis for IGHD in three families from the Indian subcontinent. The prevalence and heterogeneity of defects in the GHRHR gene are not known. Twenty-two dwarf members of a large, extended kindred containing at least 105 affected members with autosomal recessive short stature underwent extensive endocrine evaluation, which confirmed markedly reduced or undetectable serum concentrations of GH that did not increase in response to different stimuli. DNA sequences of the 13 exons and intron-exon boundaries of the GHRHR gene were determined in an index patient. A novel homozygous 5' splice site mutation (G-->A at position +1) in IVS1 was found. Thirty of the affected subjects tested were homozygous for this mutation, and 64 clinically unaffected patients were either heterozygous for the mutation (n = 41, including 9 obligate carriers) or homozygous for the wild-type sequence (n = 23). We describe a novel mutation in the GHRHR gene as cause of dwarfism in the largest kindred with familial IGHD described to date.

Suppression of growth hormone does not affect ongoing spermatogenesis in rats.

Recent evidence suggests that growth hormone (GH) may enhance physiologic processes, such as spermatogenesis, in addition to causing classical anabolic effects. We have previously shown that testosterone restores spermatogenesis in rats that were made azoospermic by immunization against gonadotropin-releasing hormone (GnRH). In this study, we investigated whether suppression of GH affects spermatogenesis and the ability of testosterone to restore spermatogenesis following immunization against GnRH and/or growth hormone-releasing hormone (GHRH). Twelve rats were actively immunized against GnRH (anti-GnRH), twelve rats were actively immunized against GHRH (anti-GHRH), six rats were immunized against both GnRH and GHRH (anti-GnRH/GHRH), and six rats served as controls. Two weeks after the second booster, six rats each from the anti-GnRH and anti-GHRH groups as well as the six anti-GnRH/GHRH rats received 24-cm testosterone-filled Silastic implants (T), and the remaining six rats from each of these groups received empty Silastic implants. All rats were euthanized 2 months later. Weights of testes and testicular sperm counts were determined. Serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and insulin-like growth factor-1 (IGF-1) concentrations were determined by radioimmunoassays. Serum GH and IGF-1 were suppressed in anti-GHRH rats. IGF-1 was partially restored by testosterone in anti-GHRH and in anti-GnRH/GHRH rats, but GH was restored to control value in anti-GnRH/GHRH rats. Serum LH and FSH were suppressed in anti-GnRH and anti-GnRH/GHRH rats, but only FSH was partially restored by testosterone. Suppression of GH did not affect maintenance of spermatogenesis. However, because T partially restored GH and IGF-1 levels in anti-GnRH/GHRH rats and because spermatogenesis was found to be restored in these rats, we conclude that GH does not play a role in the maintenance of spermatogenesis in adult rats, but it may be required for the replenishment of germ cells in experimentally induced regressed rat testes.

Effect of opioid blockade on insulin and growth hormone (GH) secretion in patients with polycystic ovary syndrome: the heterogeneity of impaired GH secretion is related to both obesity and hyperinsulinism

Objective: To investigate the involvement of opioid tone, obesity, and hyperinsulinemia in GH secretion in women with polycystic ovary syndrome (PCOS). Design: Controlled clinical study. Setting: Catholic University of Sacred Heart School of Medicine in Rome, Italy. Patient(s): Twenty-two patients with PCOS and 14 healthy, normally ovulating volunteers, matched for age and body mass index. Intervention(s): Patients underwent a GH-releasing hormone (GHRH) test and an oral glucose tolerance test before and after 4–5 weeks of treatment with 50 mg/d of naltrexone. Main Outcome Measure(s): Serum concentrations of GH, insulin, glucose, steroids, and gonadotropins, as well as the GH area under the curve (AUC-GH) and the insulin area under the curve (AUC-I), were measured before and after naltrexone treatment. Result(s): In patients with PCOS, the administration of naltrexone increased the GH response to the GHRH test without interfering with the insulin response to the oral glucose tolerance test. However, the GH response to the GHRH test was improved significantly only in lean patients with PCOS, whereas obese patients with PCOS did not show any improvement in GH secretion. In obese control subjects, the treatment reduced plasma basal insulin concentrations and increased the AUC-GH, whereas in lean control subjects, the treatment reduced the GHRH-induced response. In normoinsulinemic patients with PCOS, the GH response to the GHRH test increased significantly after treatment, whereas the AUC-I was not affected. In hyperinsulinemic patients with PCOS, treatment with naltrexone significantly reduced the AUC-I, whereas the AUC-GH increased only in lean hyperinsulinemic patients with PCOS. Conclusion(s): Naltrexone treatment improves GHRH-induced GH secretion in patients with PCOS. However, this GH response is heterogeneously represented in relation to both obesity and hyperinsulinism.

Arginine infusion and/or acute changes of growth hormone levels do not acutely alter leptin serum levels.

Leptin, the ob gene product, is produced by differentiated adipocytes. It functions as an afferent signal to the central nervous system indicating satiety and fat mass status. It acts upon the hypothalamic-pituitary axis. Growth hormone (GH) secretion is thought to be stimulated by leptin. Conversely, leptin secretion and ob gene expression are regulated by classical neuroendocrine networks. Whether or not acute changes of GH concentrations directly alter leptin serum levels in vivo is still debated. We investigated whether or not acute changes in GH serum concentrations during arginine infusion (0.5 g/kg b. wt.) alter leptin serum levels in 45 children and adolescents (33 M, 12 F). GH and leptin serum levels were determined at -30, 0, 30, 60, 90, 120 min after arginine infusion using specific radioimmunoassays. Leptin serum concentrations remained unaltered throughout the arginine infusion in all children and adolescents whether or not GH secretion was normal. (1) Acute changes of GH levels do not alter leptin serum levels during acute arginine infusions over 120 min. (2) Arginine does not acutely modulate leptin secretion.

Epidemiology of acromegaly.

Acromegaly is a consequence of chronic growth hormone (GH) excess, due in the majority of cases to a GH-secreting pituitary adenoma, and occurring with a population prevalence of 60 per million and an incidence of 3-4 per million per year. Males and females appear to be equally affected with an average age of presentation of 44 years. Younger patients may have more aggressive tumours and higher GH concentrations. There is co-existent hyperprolactinaemia in about one third of cases, and a variable proportion of [figure: see text] tumours appear to have activating mutations of the gsp gene or other genetic abnormalities. Acute complications such as carpal tunnel syndrome, sweating and obstructive sleep apnoea are usually readily reversible with treatment of the condition, but chronic complications such as hypertension, diabetes and heart disease are less readily corrected and post-treatment GH levels of < 2.5 ug/L (5 mU/L) are needed to achieve the prevalence found in the general community. Such 'curative' levels of GH are achieved in only about 50% of patients with current therapies, and as a result there is an ongoing excess of patients with chronic complications of acromegaly leading to increased morbidity and mortality from the disorder, with observed-to-expected mortality ratios ranging from 1.6-3.3 and only approaching unity in those with growth hormone levels < 2.5 ug/L following treatment. Prognostic factors include in some studies the presence of diabetes and [table: see text] hypertension prior to diagnosis as well as measures of exposure to excessive growth hormone derived from the product of preoperative serum GH and the time from first symptoms to treatment. Overall, however, the most important prognostic variable appears to be the serum GH concentration achieved by treatment, with an increasing consensus that this needs to be < 2.5 ug/L (5 mU/L) to achieve cure of the condition.

Correlation between longitudinal bone growth, growth hormone, and insulin-like growth factor-I in prepubertal dogs

Abstract Objective To determine the association between longitudinal bone growth and concentrations of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in serum from prepubertal dogs. Animals 6 male 14-week-old German Shepherd Dogs. Procedure Blood was obtained every 30 minutes for 14 consecutive days. Concentrations of GH and IGF-I in serum were determined, using a canine-specific radioimmunoassay and conventional radioimmunoassay after acid-ethanol extraction, respectively. Simultaneous biplanar radiography was performed daily to measure bone growth. Spectral analysis was used to estimate specific features of GH secretion during an extended period. Multiple linear regression with different lag times between independent and dependent variables was used to determine the strongest predictors of bone growth. Results The power spectra of GH concentrations in serum had a primary peak at a frequency of 0.02 cycles/h or a periodicity of 50 h/cycle. A significant determinant of longitudinal bone growth was a lag time of 1 day in concentration of GH in serum. The relationship between IGF-I concentration in serum and bone growth was not significant. Conclusions The primary frequency of GH secretion is outside the time frame of a single day and the concentration of GH in serum is a primary determinant of bone growth. Clinical Relevance A better understanding of the components of bone growth provide discernment to improved diagnosis and treatment of abnormal bone growth. (Am J Vet Res 1998;59:1608-1612)

Effects of endotoxin lipopolysaccharide administration on the somatotropic axis

The aim of this work was to study the effect of chronic activation of the immune system on the somatotropic axis. Accordingly, the changes in growth hormone (GH) secretion, circulating insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) in response to endotoxin lipopolysaccharide (LPS) administration were examined in adult male Wistar rats. Acute LPS injection (2.5, 25 or 250 microg/kg) increased serum corticosterone in a dose-dependent manner and decreased serum levels of insulin and IGF-I, serum GH concentration declined linearly as the LPS dose increased. Western ligand blot showed an increase in the 33 kDa band (corresponding to IGFBP-1 and IGFBP-2) in the rats that received the highest dose of LPS (250 microg/kg). Chronic LPS administration (250 microg/kg daily for 8 days) significantly decreased body weight, serum levels of IGF-I and pituitary GH content, whereas it increased circulating IGFBP-3 (47 kDa band), IGFBP-1 and IGFBP-2 (33 kDa band) and the 24 kDa band (which possibly corresponds to IGFBP-4). Serum concentration of corticosterone and hypothalamic somatostatin content were also increased by chronic LPS treatment. These data suggest that the decrease in GH and IGF-I secretion and the increase in circulating IGFBPs are important mechanisms in body weight loss during chronic inflammation.

Seasonal regulation of prolactin secretion in hypophyseal stalk transected beef calves.

Seasonal regulation of prolactin secretion was investigated in crossbred beef heifer calves. Calves were randomly assigned to hypophyseal stalk transection (HST, n = 6) or sham-operation control (SOC, n = 6) groups and fitted 1 day before surgery with an indwelling external jugular catheter. Prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), thyroxine (T4), and tri-iodothyronine (T3) in peripheral serum were measured by radioimmunoassay in samples obtained before and after HST or SOC. During the first 8 days after HST, PRL concentrations remained significantly greater than SOC, but then decreased in both HST and SOC calves to 4 +/- 2 (+/- SE) and 10 +/- 3 ng/ml, respectively (P < 0.001). PRL remained low in both HST and SOC groups for three months after surgery. By four months, HST calves had lower basal PRL (5 +/- 1 ng/ml) than observed in SOC (40 +/- 4 ng/ml), and seasonal changes in PRL blood concentration also were attenuated by HST. Although HST reduced PRL secretion, it did not abolish the effect of seasonal changes (P < 0.01); circulating PRL concentration increased six-fold by shifts in photoperiod and temperature from winter to summer in these stalk-transected calves. The SOC group had higher serum GH during the winter (3.8 +/- 0.8) than in July (1.3 +/- 0.03 ng/ml). The HST group had the opposite profile of GH concentration, however, with concentrations being higher during May through July. Thyroid stimulating hormone secretion was partly sustained after stalk transection possibly by negative feedback of reduced circulating thyroxine and tri-iodothyronine. These results in both hypophyseal stalk-transected and sham-operated beef calves maintained in a natural environment strongly suggest that hypothalamic regulation of PRL secretion by adenohypophyseal cells is extremely sensitive to seasonal changes throughout the year. Additionally, immediately after HST, PRL blood concentration remains significantly greater than in SOC calves but eventually decreases to low blood concentration in HST calves, and unlike that seen after HST in primates. Regardless, basal PRL serum concentration responds to seasonal changes, but a less distinct change in basal GH serum concentration in HST calves than seen in the SOC calves.

Effects of delmadinone acetate on pituitary-adrenal function, glucose tolerance and growth hormone in male dogs.

To characterise the effects of delmadinone acetate on the pituitary-adrenal axis, glucose tolerance and growth hormone concentration in normal male dogs and dogs with benign prostatic hyperplasia. A prospective study involving nine normal male dogs and seven with prostatic hyperplasia. Delmadinone acetate was administered to six normal male dogs and seven dogs with benign prostatic hyperplasia at recommended dose rates (1.5 mg/kg subcutaneously at 0, 1 and 4 weeks). Three normal controls received saline at the same intervals. Blood concentrations of ACTH, cortisol, glucose, insulin and growth hormone were measured over 50 days. Intravenous glucose tolerance and ACTH response tests were performed before and after treatment in the nine normal animals. A substantial suppression of basal and 2 h post-ACTH plasma cortisol secretion was demonstrated after one dose in all dogs given delmadinone acetate. Individual responses after the second and third administration varied between recovery in adrenal responsiveness to continued suppression. Plasma ACTH concentration was also diminished after one treatment. No effects were evident on glucose tolerance or serum growth hormone concentrations. Delmadinone acetate causes adrenal suppression from inhibition of release of ACTH from the pituitary gland. Treated dogs may be at risk of developing signs of glucocorticoid insufficiency if subjected to stressful events during or after therapy. Neither glucose intolerance nor hypersomatotropism seems likely in male dogs given delmadinone acetate at the recommended dose rate, but the potential for excessive growth hormone secretion in treated bitches remains undetermined.

Stimulation of Dopamine D 1 Receptors Increases Activity of Periventricular Somatostatin Neurons and Suppresses Concentrations of Growth Hormone

The selective dopamine D 1 receptor agonist, SKF38393, stimulates release of somatostatin (SS) from perifused bovine hypothalamic slices. Therefore, we hypothesized that SKF38393 activates SS neurons, which, via release of SS, would suppress concentrations of growth hormone (GH) in serum in calves. Our objectives were to determine whether SKF38393: (1) increases the percent of immunoreactive c-Fos protein and Fos-related antigens (Fos/FRA) detected in somatostatin neurons in periventricular (PeVN) and arcuate (ARC) hypothalamic nuclei; (2) reduces concentrations of GH in serum; (3) suppresses growth hormone-releasing hormone (GHRH)-induced release of GH. Meal-fed steers were used to perform these objectives because a synchronous pulse of GH occurs 1–2 hr before feeding in steers allowed access to feed for 2 hr each day. In Experiment 1, two groups of four Holstein steers were injected s.c. with either vehicle (sterile water) or SKF38393 (5 mg/kg BW). Steers were injected i.v. with a lethal dose of sodium pentobarbital 100 min later and their brains were fixed with 4% paraformaldehyde. Dual-label immunohistochemistry was performed on 40 μm free-floating sections using antiserum to SS and to Fos/FRA on sections containing PeVN and ARC nuclei. More SS neurons were detected in the PeVN than in the ARC. The percent of SS neurons with immunoreactive Fos/FRA present was 2.9-fold higher in SKF38393-treated compared with vehicle-injected steers in the PeVN, but was unchanged in the ARC. In Experiment 2, eight Holstein steers were injected s.c. with either vehicle (sterile water) or SKF38393 (5 mg/kg BW) 140 min before meal-feeding. In contrast to controls, concentrations of GH in serum of SKF38393-treated steers did not increase during the 140 min before meal-feeding. In Experiment 3, eight Holstein steers were injected s.c. with either vehicle (sterile water) or SKF38393 (5 mg/kg BW), then 100 min later, each steer was injected i.v. with [Leu 27, Hse 45] bGHRH 1–45 lactone (0.2 μg/kg BW). Bovine GHRH stimulated release of GH into serum in both groups, but concentrations of GH were lower in SKF38393-treated steers. These results show that stimulation of D 1 receptors selectively increases activity of SS neurons in the PeVN, and this increased activity is associated with suppressed basal- and GHRH-induced release of GH in serum of meal-fed steers.

8 Acquired growth hormone resistance in adults

Acquired growth hormone resistance (AGHR) may be defined as the combination of a raised serum growth hormone (GH) concentration, low serum insulin-like growth factor-1 (IGF-1) concentration and a reduced anabolic response to exogenous GH. A wide range of conditions exhibit the syndrome to a variable degree, including sepsis, trauma, burns, AIDS, cancer, and renal or liver failure. The primary defect seems to be a reduction in IGF-1 concentration which then leads to increased GH concentration by a loss of negative feedback. It is not clear whether IGF-1 concentration falls because of decreased production or increased clearance from the circulation, or both. Treatment to reverse the biochemical defect by restoring IGF-1 levels, either by the administration of GH or IGF-1, has resulted in improvements in a wide range of metabolic parameters and, more recently, to definite clinical benefit in well-defined groups, such as patients with AIDS. These results cannot be extrapolated to other groups with AGHR as a recent unpublished report suggested increased mortality in critically ill patients treated with GH. Research needs to focus on the molecular basis of AGHR if we are to develop therapies for catabolism.

Morphometric and Functional Changes of Rat Pituitary Somatotropes and Lactotropes after Central Administration of Somatostatin

This study examined effects of intracerebroventricularly (i.c.v.) administered somatostatin (SRIH-14 and SRIH-28) on growth and function of pituitary somatotropes (GH cells) and lactotropes (PRL cells). Male rats received three i.c.v. injections (1 µg/5 µl) of SRIH-14 or SRIH-28 every second day. Blood samples were collected for hormone assays and pituitaries were removed for histological and morphometric evaluation 5 days after the last i.c.v. treatment. Compared to control animals, SRIH treatment decreased (p < 0.05) pituitary weight and all morphometric measurements obtained in GH and PRL cells. Concentrations of serum growth hormone (GH) and prolactin (PRL) in both SRIH-treated groups were also lower (p < 0.05) than in control rats. These findings suggest that centrally administered somatostatin is specifically involved in the control of growth and secretory activity of GH and PRL cells. Thus, pharmacological manipulation of SRIH receptors reached from cerebrospinal fluid may alter systemic effects of GH and PRL.

Marked gender differences in ambulatory morning growth hormone values in young adults

The influence of gender on serum concentrations of growth hormone (GH) and 12 other endocrine analytes was investigated in sera drawn from 291 healthy medical students in the ambulatory state in the morning, after fasting overnight. GH was measured with a sensitive noncompetitive fluoroimmunoassay. The median GH value was 80-fold higher in women 21-26 years old than in age-matched men (14.4 vs 0.18 mIU/L), compared with a female/male ratio of 2.2 for 17beta-estradiol and a male/female ratio of 14 for testosterone. Furthermore, the values for sex hormone-binding globulin, follicle-stimulating hormone, luteinizing hormone, prolactin, and insulin-like growth factor 1 (IGF-1) were higher, whereas the values for free thyroxine, triiodothyronine, thyroid-stimulating hormone, and parathyroid hormone were lower in the women. The median GH value was 68-fold higher in women 27-43 years old than in age-matched men (10.9 vs 0.16 mIU/L). Women taking contraceptives with ethinyl estradiol and desogestrel or levonorgestrel had higher GH values, and the desogestrel group had lower IGF-1 values than women not taking contraceptives. The median GH values in these groups were 125- and 117-fold higher, respectively, than in men 21-26 years old. The results suggest that routine morning activity produces a marked GH response in >90% of young women but in very few age-matched men. The effect on GH was even more pronounced in women taking oral contraceptives, suggesting that the intake of ethinyl estradiol contributes to higher GH concentrations in these women.

Hormonal profiles of callipyge and normal sheep.

Five sheep expressing the callipyge gene, which causes muscle hypertrophy, were compared with five normal sheep to determine whether endocrine differences existed between genotypes. Blood samples were taken at 15-min intervals for 6 h to measure serum concentrations of growth hormone and insulin. Thyroxine and IGF-I levels were determined in single samples. No differences were found in mean serum growth hormone concentrations, growth hormone pulse amplitude, or pulse frequency (P > .3). Insulin concentrations were not different between genotypes before or after feeding (4.5 +/- 1.3 ng/mL callipyge vs 4.9 +/- 1.7 ng/mL normal, P > .4). The IGF-I concentrations did not differ (273.8 +/- 17.6 ng/mL callipyge vs 261.4 +/- 12.3 ng/mL normal). Serum thyroxine concentrations also were not different (5.9 +/- 2.3 microg/mL for callipyge vs 5.1 +/- 2.1 microg/mL normal, P > .3). In a separate experiment, five ewe lambs with and five without the callipyge gene were stressed to determine whether the adrenocortical response to stress differed between genotypes. Blood samples were taken at 15-min intervals for 2 h before, during, and after restraint stress. Restraint increased serum cortisol concentrations in both groups (P < .001), but genotypes did not differ at any time (P > .3). These results suggest that differences in muscling are not due to differences in systemic hormone secretion. The results of the second experiment indicate that callipyge and normal sheep have similar adrenocortical responses to stress.

Postpartum Hyperprolactinemia and Hyporesponsiveness of Growth Hormone (GH) to GH-Releasing Peptide

Human PRL and GH as well as their respective receptors have closely related origins. In peripartal women, physiological hyperprolactinemia is associated with a pronounced hyposomatotropism that remains to be fully characterized. Through paracrine mechanisms, PRL-secreting“ pregnancy cells” may modulate the secretory function of somatotropes, which are known to express PRL receptors. Within a randomized, placebo-controlled design, we examined GH responsiveness in 10 nonpregnant women and in 58 mothers either in early (median, 48 h; range, 42–54 h after delivery; all lactating) or late postpartum (median, 10 weeks; range, 3–25 weeks; lactating and nonlactating subgroups), using GH-releasing peptide-1 (GHRP-1; 100-μg iv bolus) as the GH secretagogue. Baseline serum PRL concentrations were low and similar (median, 5μ g/L) in nonpregnant controls and nonlactating, late postpartum women and were elevated in lactating women, particularly in the early postpartum period (median, 102 μg/L), compared to those in the late postpartum period (median, 27 μg/L). GHRP-1 elicited GH responses in all study groups; lactation was associated with lower and slower GH responses. Serum GH concentrations (20 min after GHRP-1 treatment) in controls (median, 78 μg/L) were 7- and 5-fold higher than those in lactating women studied, respectively, early or late postpartum. Baseline prolactinemia presented an inverse correlation with GH responsiveness; the higher baseline PRL concentration, the lower and the slower the GH response to GHRP-1. GH hyporesponsiveness in postpartum women is herewith further characterized to include the GHRP pathway. The inverse relationship between baseline prolactinemia and GH responsiveness is consistent with the concept that pregnancy cells may exert, either directly or indirectly, an inhibitory effect on the secretory capacity of somatotropes.

Étude de l'axe somatotrope des nouveau-nés à terme et prématurés pendant le premier mois de vie

Neonatal somatotropic function is characterized by a discrepancy between elevated growth hormone (GH) levels and low IGF I levels. This study aimed at explaining this discrepancy, particularly to examining if it could result from low GH bioactivity. Serum concentrations of bioactive GH (bio GH), GH measured by radioimmunoassay (riGH), GH binding protein (GHBP), IGF I and IGF binding proteins (IGFBP) were determined in 27 premature and term newborns during the first month of life. At day 4, riGH and bio GH concentrations were elevated in both premature and term newborns as compared with normal prepubertal children; GHBP and IGF I levels were low, with a positive correlation with gestational age (P < 0.001). There was a positive correlation between GHBP and IGF I levels. IGFBP-1 and IGFBP-2 levels were elevated and negatively correlated with gestational age (P < 0.005). IGFBP-3 levels were within the range of prepubertal children values and positively correlated with gestational age (P < 0.005). During the first month, riGH and bio GH levels decreased in all infants, while IGFI levels increased in premature infants only, and GHBP levels in term infants only. The elevated levels of bio GH during the first days of life appear to be related to the low levels of IGF I due to a reduced number or function of GH receptors. In premature infants the decrease in GH levels observed afterwards appears to be secondary to the increase in IGF I levels. In term infants, in the absence of increase in IGFI levels other(s) factor(s) seem(s) to be involved.

GSM radiocellular telephones do not disturb the secretion of antepituitary hormones in humans.

It is known that the endocrine system of experimental animals is susceptible to perturbation by radiofrequency (RF) radiation. Because of the recent interest in health and safety issues of cellular telephones, an experiment was designed to evaluate the effect of a 900 MHz RF radiation emitted by a Global System for Mobile radiotelephone (217 Hz impulses, one-eighth duty cycle, 2 W peak power) on human endocrine functions. Twenty healthy male volunteers aged from 19 to 40 were inducted in the present experiment. Each subject was exposed to RF radiation through the use of a cellular phone 2 h/day, 5 days/wk, for 1 month. Subjects were their own control. End points were serum adrenocorticotropin, thyrotropin, growth hormone, prolactin, luteinizing hormone, and follicle stimulating hormone concentrations. These end points were determined in nine weekly blood samples obtained starting 3 weeks before the commencement of the exposure and ending 2 weeks after exposures. All but one blood sample was drawn 48 h after each weekly session. The seventh drawing was performed the morning after the last weekly exposure. Within each individual, the preexposure hormone concentration was used as a control. Results indicated that all hormone concentrations remained within normal physiologic ranges. A difference was not noted among the nine weekly samples in five of six hormones studied. There was a significant change only in thyrotropin concentration, showing a 21% decrease on the seventh sampling. Because this change recovered fully during the postexposure period, it is concluded that 1 month of intermittent exposures to RF radiation from a cellular telephone does not induce a long-lasting or cumulative effect on the hormone secretion rate of the anterior pituitary gland in humans.

The Prenatal Attenuation of Brain/Body Development Through Interactions Between Growth Hormone, Triiodothyronine and Testosterone During Prenatal Development of Female Neonates

The relations of serum growth hormone (GH), free testosterone (T), and free triiodothyronine (T3) concentrations to the head circumference, height, and weight were studied in the human neonates. Blood was taken from the umbilical cord immediately after the birth, to measure the hormone concentrations. GH was found to be inversely correlatd with the bodily measures in the female neonates; there were no significant correlations between these variables in males. In females, free T3 negatively linearly correlated with GH, and positively linearly correlated with the neonatal head circumference, height, and weight. Serum free T levels was found to be positively linearly correlated with GH, and negatively linearly correlated with the neonatal body measures in the same subjects. It was suggested that GH may exert growth reducing effects through T3 and T during perinatal development.

Interactions of insulin-like growth factor (IGF)-II and growth hormone in vivo: circulating levels of IGF-I and IGF-binding proteins in transgenic mice.

To study interactions between insulin-like growth factor-II (IGF-II) and growth hormone (GH) in vivo, we crossed hemizygous transgenic mice carrying phosphoenolpyruvate carboxykinase (PEPCK)-IGF-II fusion genes with hemizygous PEPCK-bovine GH (bGH) transgenic mice. Offspring harbouring both transgenes (IB), the IGF-II transgene (I) or the bGH transgene (B), and non-transgenic littermates (C) were obtained. Blood samples were taken before (end of week 12) and after (end of week 14) the mice had received a diet high in protein and low in carbohydrates to stimulate PEPCK promoter-controlled transgene expression. Mean serum GH concentrations of both B and IB mice corresponded to 900 ng/ml and increased more than twofold (P < 0.001) after 1 week of the high-protein diet. GH concentrations in controls and I mice were less than 20 ng/ml. Serum IGF-II concentrations in I and IB mice were three-to fourfold higher than those in C and B mice. Whereas IGF-II concentrations were not changed by the high-protein diet in the last two groups, serum IGF-II increased significantly in I (P < 0.001) and IB mice (P < 0.05). This increase was significantly (P < 0.05) less pronounced in IB than in C and I mice. Circulating IGF-I concentrations were about twofold (P < 0.001) higher in B and IB than in C and I mice, and showed a tendency to be lower in I than in C and in IB than in B mice when animals were maintained on the standard diet. The high-protein diet did not change circulating IGF-I concentrations in controls and B mice, but resulted in a significant reduction of serum IGF-I concentrations in I (P < 0.05) and IB mice (P < 0.001). Consequently, after PEPCK-IGF-II transgene expression was stimulated, serum IGF-I concentrations were significantly (P < 0.05) lower in I than in C and in IB than in B mice. Serum IGF-binding protein (IGFBP)-2 concentrations were significantly (P < 0.05) higher in I mice than in all other groups when mice were maintained on the standard diet, with a tendency to reduced IGFBP-2 concentrations in B mice. After the high-protein diet, serum IGFBP-2 concentrations did not change in C and I mice, but increased by two- to threefold in B and IB mice (P < 0.001). Serum IGFBP-3 concentrations tended to be greater in B and IB than in C and I mice, but these differences were mostly not significant. IGFBP-4 concentrations were significantly (P < 0.001) increased by GH overproduction in B and IB mice. Our data suggest that the reduction in circulating IGF-I concentrations by increased IGF-II is most probably due to the limited serum IGF binding capacity and the short half-life of free IGFs, rather than to a reduction in GH-dependent IGF-I production. Effects of GH overproduction on serum IGFBP-2 concentrations depend on dietary factors and may be both inhibitory and stimulatory.

A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse).

Laron syndrome [growth hormone (GH) insensitivity syndrome] is a hereditary dwarfism resulting from defects in the GH receptor (GHR) gene. GHR deficiency has not been reported in mammals other than humans. Many aspects of GHR dysfunction remain unknown because of ethical and practical limitations in studying humans. To create a mammalian model for this disease, we generated mice bearing a disrupted GHR/binding protein (GHR/BP) gene through a homologous gene targeting approach. Homozygous GHR/BP knockout mice showed severe postnatal growth retardation, proportionate dwarfism, absence of the GHR and GH binding protein, greatly decreased serum insulin-like growth factor I and elevated serum GH concentrations. These characteristics represent the phenotype typical of individuals with Laron syndrome. Animals heterozygous for the GHR/BP defect show only minimal growth impairment but have an intermediate biochemical phenotype, with decreased GHR and GH binding protein expression and slightly diminished insulin-like growth factor I levels. These findings indicate that the GHR/BP-deficient mouse (Laron mouse) is a suitable model for human Laron syndrome that will prove useful for the elucidation of many aspects of GHR/BP function that cannot be obtained in humans.