EFFECT OF THYROXINE REPLACEMENT THERAPY ON PLASMA INSULIN-LIKE GROWTH FACTOR 1 LEVELS AND GROWTH HORMONE RESPONSES TO GROWTH HORMONE RELEASING FACTOR IN HYPOTHYROID PATIENTS

The aim of this study was to evaluate the effect of T4 replacement therapy on plasma insulin-like growth factor 1 (IGF-1) levels in patients with primary hypothyroidism to see whether recovery of pituitary GH responsiveness to GRF was associated with increased plasma IGF-1 levels. IGF-1 levels and GH responses to GRF (1 μg/kg) were measured in 21 patients with primary hypothyroidism before and after T4 replacement therapy. T4 increased plasma IGF-1 levels (57.2 ± 4.4 vs 75.9 ± 8-8 ng/ml, mean ± SEM, P <0.05) and GH responses to GRF as assessed both by peak GH levels (9 ± 1.5 ng/ml before treatment vs 16.7 ± 3 ng/ml after treatment, mean ± SEM, P <0.05) and area under curve (496 ± 92 before treatment vs 896 ± 161 after treatment, mean-± SEM, P < 0.05). Linear regression analysis showed a positive correlation between free T3 and IGF-1 levels after treatment ( r = 0-37, P <0.05) and a negative relationship between plasma IGF-1 levels before treatment and a IGF following T4 replacement therapy ( r = 0.45, P < 0.025). However, no correlation was found between plasma IGF-1 levels and GH responses to GRF, suggesting that GH responses to GRF are of no predictive value in relation to the recovery of plasma' IGF-1 levels following T4 replacement therapy in hypothyroid patients.     

血清胰岛素样生长因子结合蛋白与肾病大鼠的生长障碍

目的：探讨营养不良、肾病本身的糖皮质激素作为各自独立因素对大鼠血清胰岛素生长因子结合蛋白（ＩＣＦＢＰｓ）浓度的影响，阐明血清ＩＧＦＢＰｓ代谢紊与肾病综合片（ＮＳ）大鼠生长障碍的关系。方法：２４只周龄相同体重相近的雄笥ＳＤ大鼠随机分成正常、食物对照、阿霉素现任地塞米松治疗的阿霉素肾病四组。血清ＩＧＦＢＰＳ浓度和肝脏ＩＧＦＢＰｓｍＲＮＡ表达分别采用Ｗｅｓｔｅｒｎｌｉｇａｎｄｂｌｏｔ和ＲＴ－ＰＣＲ法检测     

INSULIN-LIKE GROWTH FACTOR 1 AND BONE TURNOVER IN GLUCOCORTICOID-TREATED AND CONTROL SUBJECTS

The role of the growth hormone-somatomedin axis in the genesis of steroid osteoporosis has been studied by measuring circulating insulin-like growth factor 1 (IGF-1) levels in asthmatic subjects either receiving or not receiving therapy with oral glucocorticoids. There was no difference in IGF-1 levels between the two groups (60.6 micrograms/l (95% confidence interval 47.3-77.8) in the control subjects vs 69.1 micrograms/l (49.3-96.9) in the steroid-treated group). IGF-1 declined with age in the control subjects but not in those taking steroids. When IGF-1 levels were correlated with biochemical indices of bone turnover, a significant relationship was found with urine hydroxyproline in the control subjects (r = 0.55, P less than 0.02) but not in those taking steroids. It is concluded that glucocorticoid therapy does not alter mean circulating levels of IGF-1 but that the growth hormone-somatomedin axis may influence bone turnover in normal subjects. Interference by glucocorticoids with the normal regulation of IGF-1 and its influence on bone turnover is suggested.     

INAPPROPRIATELY ELEVATED PLASMA INSULIN-LIKE GROWTH FACTOR II IN RELATION TO SUPPRESSED INSULIN-LIKE GROWTH FACTOR I IN THE DIAGNOSIS OF NON-ISLET CELL TUMOUR HYPOGLYCAEMIA

The diagnosis of non-islet cell tumour (hypoinsulinaemic) hypoglycamia has been complicated by contradictory biochemical evidence. Although insulin-like growth factor II (IGF-II) has been identified as the hypoglycaemic agent, plasma levels are often not elevated. In this study specific radioimmunoassay procedures for the measurement of IGF-I and IGF-II are described. Reference data on plasma IGF-II concentrations in relation to a wide range of IGF-I levels have been accumulated using plasma samples from acromegalic, hypopituitary and insulinoma (i.e. hyperinsulinaemic hypoglycaemia) patients as well as normal subjects from all age groups. The reference data indicate that a low plasma IGF-I value is normally associated with a relatively low plasma IGF-II level. Within a group of hypoinsulinaemic hypoglycaemia patients, a small number, invariably with evidence of a neoplasm, had low plasma IGF-I concentrations but apparently normal IGF-II levels. We propose that, in such cases, an apparently normal plasma IGF-II value is inappropriately high for the low plasma IGF-I level and, in association with non-ketotic hypoinsulinaemia and suppressed plasma growth hormone (GH), is diagnostic of a non-islet cell tumour as the cause of hypoglycaemia.     

INSULIN-LIKE GROWTH FACTOR I (IGF-I) IN HEALTHY CHILDREN, ADOLESCENTS AND ADULTS AS DETERMINED BY A RADIOIMMUNOASSAY SPECIFIC FOR THE SYNTHETIC 53–70 PEPTIDE REGION

A radioimmunoassay (RIA) specific for the synthetic 53-70 peptide region of human insulin-like growth factor I (IGF-I) was used to determine IGF-I in the serum of 191 healthy newborns, children and adolescents and in 26 adults. The results compare favourably with reported values obtained using RIA systems for the native IGF-I molecule. Intra- and inter-assay CV were 3.3 and 7.2% respectively. In childhood, mean +/- SD IGF-I levels rise from 6.0 +/- 3.5 nmol/l in newborns to 16.5 +/- 4.0 nmol/l at 8-11 years in both sexes. At the onset of puberty, IGF-I levels in females (24.9 +/- 6.6 nmol/l) are significantly (P greater than 0.005) higher than in males (17.2 +/- 4.2 nmol/l). With further pubertal development IGF-I levels continue to rise, reaching peak values at pubertal stage P4 (40.6 +/- 4.5 nmol/l in males, 42.8 +/- 5.1 nmol/l in females) and decline thereafter to lower values during adulthood: 16.5 +/- 5.8 nmol/l (males) and 24.2 +/- 7.0 nmol/l (females) (P greater than 0.001). In pubertal males, IGF-I correlates significantly with height (r = 0.66, P less than 0.001), bone age (r = 0.69, P less than 0.001) and growth velocity (r = 0.64, P = 0.025) as well as with testosterone levels (r = 0.69, P less than 0.001). In pubertal females a significant correlation is found between IGF-I and height (r = 0.55, P less than 0.020). The ready availability of a simple, precise and reproducible IGF-I RIA, should contribute much to evaluating the importance of IGF-I measurements in normal growth and in the diagnosis and therapy of various growth disorders.     

PRODUCTION OF BINDING PROTEINS AND ROLE OF THE INSULIN-LIKE GROWTH FACTOR I BINDING PROTEIN 3 IN HUMAN ARTICULAR CARTILAGE EXPLANTS

The aim of this study was to determine the production of insulin-likegrowth factor binding proteins (IGFBP) and the role of the IGFBP-3in human normal (n = 2) and osteoarthritic (OA) articular cartilage(n = 14) explants. Binding proteins were studied in the mediumby Western ligand blotting and Western blotting. Proteoglycansynthesis under insulin-like growth factor I (IGF-I) stimulationwas studied after a pulse of ³⁵SO^2–₄ in the presence orabsence of added IGFBP-3. Osteoarthritic explants released adoublet of IGFBPs with a 39/43 kDa M_r corresponding to the bindingprotein 3. Constitutive production from unstimulatcd OA cartilagewas higher than from normal cartilage. IGF-1 induced a 20-foldincrease and IL-1 a 2-fold increase in IGFBP-3 release. A minorband around 30 kDa was also detectable. Studies of proteoglycan(PG) synthesis showed that the majority of OA cartilage explantsamples responded weakly to IGF-I (100 ng/ml) stimulation (+33%),while the others were high responders (+180%). Co-incubationof IGF-I with recombinant (r) IGFBP-3 did not affect the rateof PG synthesis. However, while pre-incubation with rIGFBP3for 72 h did not change the rate of PG synthesis in the high-respondergroup, it strongly increased PG synthesis in the low-respondergroup. This study demonstrates that the ability of IGF-I toenhance proteoglycan synthesis varied among the OA samples andmay in part be dependent on the local level of IGFBP-3. Thisimplies pathophysiological considerations in the limits of IGF-Iaction during the OA process. KEY WORDS: Osteoarthritis, Insulin-like growth factor 1, Binding protein 3, Proteoglycan     

GROWTH HORMONE RESPONSES TO PYRIDOSTIGMINE IN NORMAL ADULTS AND IN NORMAL AND SHORT CHILDREN

There is evidence indicating that the cholinergic system positively modulates GH release probably by inhibiting somatostatinergic tone. In the present study, the effects of cholinergic enhancement by pyridostigmine, (PD), a cholinesterases inhibitor, on GH release in normal adults (n = 14) (NA) and in both normal (n = 5) (NC) and short children (n = 19) (SC) with familial short stature (n = 7) or constitutional growth delay (n = 12) were studied. In SC the insulin hypoglycaemia (IH)-induced GH increase was also studied. In both NC and SC 60 mg orally PD induced a significant GH increase with mean peak at 90 min (mean +/- SEM 11.0 +/- 2.2 ng/ml in NC and 11.2 +/- 2.3 ng/ml in SC). The GH areas under response curve (AUC) were 379.3 +/- 76.6 and 327.8 +/- 43.2 ng/ml/h in NC and SC respectively. In NA 120 mg orally PD induced a significant GH increase with mean peak at 120 min (5.1 +/- 1.1 ng/ml) which was significantly lower (P less than 0.05) than that observed in both NC and SC. This statistical difference was strengthened by evaluating AUC (NA:205.6 +/- 33.7 ng/ml/h, P less than 0.05 vs NC and SC). The correlation of drug dosage with body area ruled out that this difference could be related to the different PD dose in adults and children. In SC, IH induced a GH increase significantly lower than that observed after PD (GH peak 7.8 +/- 0.6 vs 16.4 +/- 1.9 ng/ml P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

DECREASED SEX HORMONE BINDING GLOBULIN (SHBG) AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP-1) IN EXTREME OBESITY

Obesity may be characterized by abnormal sex steroid secretion and reduced sex hormone binding globulin (SHBG) which in turn is related to fat distribution and insulin secretion. Recent in-vitro and in-vivo evidence suggests that insulin is the common mechanism regulating the secretion of SHBG and insulin-like growth factor small binding protein (IGFBP-1). IGFBP-1 appears not only to be a carrier for insulin growth factors (IGFs) but also to play an active role in growth processes, independent of growth hormone secretion. We have examined the possible relationship between fasting insulin, SHBG, testosterone, IGF-1, IGFBP-1 and fat distribution in 25 extremely obese, menstruating women (mean weight 107 +/- 3 kg) with normal glucose tolerance. Fat distribution was assessed from measurements of the waist to hip ratio (W/H). The obese women showed an elevated fasting insulin (mean +/- SEM; 21 +/- 2 mumol/l), a normal IGF-1, but reduced IGFBP-1 (14.6 +/- 2 micrograms/l); in 15 women IGFBP-1 levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24 +/- 2 nmol/l) but total testosterone values (1.9 +/- 0.1 nmol/l) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/H ratio (P less than 0.01, r2 = 0.306) and inversely correlated with SHBG (P less than 0.01, r2 = 0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio (P less than 0.001, r2 = 0.383). No correlation was found between IGFBP-1 and W/H ratio but a strong positive correlation was seen between IGFBP-1 and SHBG (P less than 0.001, r2 = 0.466). Furthermore, an equally significant inverse correlation was found between IGFBP-1 and insulin levels (P less than 0.001, r2 = 0.474).(ABSTRACT TRUNCATED AT 250 WORDS)     

FOLLICULAR FLUID CONCENTRATIONS OF INSULIN-LIKE GROWTH FACTOR 1, EPIDERMAL GROWTH FACTOR, TRANSFORMING GROWTH FACTOR-ALPHA AND SEX-STEROIDS IN VOLUME MATCHED NORMAL AND POLYCYSTIC HUMAN FOLLICLES

Thirty-three samples of follicular fluid (FF) were collected from 14 patients with the polycystic ovary (PCO) syndrome and matched for FF-volume with small follicles collected from subjects with normal ovaries. The median (range) FF concentration of insulin-like growth factor 1 (IGF1) in the group with PCO, 0.42 (0.13-1.20) U/ml was significantly higher than that of the controls, 0.33 (0.04-0.59) U/ml. All samples tested had less than 1 ng/ml of FF-epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). The patients with PCO syndrome (PCOS) had similar FF-testosterone (T) and FF-progesterone (P) concentrations to volume matched controls, but significantly higher levels of FF-androstenedione (AD) and lower FF-oestradiol (E2). These results suggest that the granulosa cells within the polycystic follicle have a functional defect in their aromatase enzyme complex.     

SERUM GROWTH HORMONE BINDING PROTEIN ACTIVITY IN HEALTHY NEONATES, CHILDREN AND YOUNG ADULTS: CORRELATION WITH AGE, HEIGHT AND WEIGHT

Serum growth hormone binding protein (GHBP) activity was estimated in healthy neonates (n = 6), children and adolescents (n = 97) and young adults (n = 19). GHBP activity was measured by incubating 125I-hGH (human growth hormone) (approximately 25,000 c.p.m.) with serum (100 microliters) in the presence and in the absence of excess unlabelled hGH, followed by separation of specifically bound 125I-hGHBP complexes from free 125I-hGH by gel filtration on Ultrogel AcA44 minicolumns. The results are expressed as the percentage specific binding relative to an adult reference serum (%RSB), after correction for endogenous hGH of the unknown serum. The between-assay coefficients of variation for two sera of %RSB activity of 51.2 and 115.4% were 6.0 and 7.0% respectively. In neonates, low values of serum GHBP were found (%RSB = 27.1 +/- 5.0 SEM) followed by a major rise during the first 6 years of life to a mean value (%RSB = 68.3 +/- 4.1 SEM) which more than doubled that of neonates. Thereafter, values rose progressively throughout childhood and puberty to reach maximum values in young adults (%RSB = 95.0 +/- 3.1 SEM). A novel observation was that serum GHBP activity correlated significantly with height standard deviation score (SDS) (males: r = 0.77, P less than 0.001; females: r = 0.56, P = 0.01) and weight SDS (P less than 0.001) for both sexes before puberty. During puberty GHBP correlated only with weight SDS in males (r = 0.60, P less than 0.01). In all age groups studied, no correlation could be found between serum GHBP and height velocity.     

STUDIES OF INSULIN-LIKE GROWTH FACTOR -I AND -II BY SPECIFIC RADIOLIGAND ASSAYS IN UMBILICAL CORD BLOOD

Somatomedin concentrations in human umbilical sera (n = 206) were measured using a specific radioimmunoassay for insulin-like growth factor (IGF)-I and a specific radioreceptor assay for IGF-II following acid-ethanol extraction of the sera to remove the somatomedin binding proteins. IGF-I concentrations were lower (P less than 0.001) than adult values and correlated with gestational age (P less than 0.001) and birth weight (P less than 0.0001). Multiple regression analysis demonstrated that both birth weight expressed independently of gestational age as the standard deviate score (P less than 0.0001) and gestational age (P less than 0.002) had effects on umbilical cord IGF-I concentrations. IGF-II concentrations were similar to adult values and did not correlate with gestational age, birth size or IGF-I values. IGF-II concentrations were higher (P less than 0.005) in male than female fetuses. These data support a role for IGF-I in influencing fetal growth and suggest the independent regulation of the secretion of IGF-I and II in the perinatal period. These was no evidence to suggest a distinct perinatal form of somatomedin.     

INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF-I BINDING PROTEIN IN THE FOLLICULAR FLUIDS OF GROWTH HORMONE TREATED PATIENTS

The presence of GH, insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), oestradiol (E2) and progesterone (PG) were investigated in the fluids obtained from various ovarian follicles of seven patients in whom the induction of super-ovulation was achieved only after GH (0.1 U/kg BW/day) was added to the gonadotrophin therapy. The follicular fluids of six patients responsive to treatment with gonadotrophin alone served as a control. In patients treated with combined therapy, the results demonstrated the presence in the follicular fluids of GH (M +/- SEM: 8.5 +/- 0.6 mU/l), E2 (771 +/- 38 nmol/l), and PG (16.4 +/- 0.7 pmol/l) in significantly higher concentrations compared to that in control follicles (6.2 +/- 0.8 mU/l, 681 +/- 30 nmol/l, and 14.4 +/- 0.6 pmol/l; P = 0.002, 0.012, 0.0001 respectively). Acid-extractable IGF-I (143 +/- 9 ng/ml) and EGF (3.9 +/- 0.3 ng/ml) concentrations were similar to those of control fluids (124 +/- 10 ng/ml and 2.9 +/- 0.7 ng/ml respectively) and were highly correlated with each other (P less than 0.001), suggesting a stimulatory effect of EGF on the local IGF-I production. A correlation between GH and IGF-I (n = 51, r = 0.36), as well as between IGF-I and PG (n = 48, r = 0.77) and E2 (n = 48, r = 0.55) was evident only in the follicular fluid of GH-treated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

THE GROWTH HORMONE INDEPENDENT INSULIN-LIKE GROWTH FACTOR-I BINDING PROTEIN BP-28 IS ASSOCIATED WITH SERUM INSULIN-LIKE GROWTH FACTOR-I INHIBITORY BIOACTIVITY IN ADOLESCENT INSULIN-DEPENDENT DIABETICS

The relationship between the growth hormone independent insulin-like growth factor binding protein (BP-28) and serum insulin-like growth factor-I (IGF-I) inhibitory bioactivity observed in diabetic serum was investigated in five poorly controlled adolescent type I diabetics. We have measured the in-vitro effects of purified BP-28 from amniotic fluid on serum IGF-I stimulated and basal cartilage sulphation and compared serum IGF-I bioactivity obtained from 24-h serum profiles from each diabetic subject with serum concentrations of BP-28 and IGF-I measured by specific radioimmunoassays. Purified BP-28 inhibited serum IGF-I stimulated and basal cartilage sulphation in vitro, in a dose-dependent manner. Serum IGF-I bioactivity of diabetic sera showed a change in activity over the 24-h period, with peak inhibitory bioactivity observed in each subject between 0800 and 1000 h. BP-28 concentrations in each individual showed a marked circadian rhythm with maximum peak levels occurring at 0800 h. Long-acting insulin administered in the evening in two of the diabetic subjects blunted the maximum peak level attained compared to the three diabetics who had long-acting insulin administered in the morning. IGF-I concentrations did not change over the 24-h period in each individual. The data shows that BP-28 inhibits serum IGF-bioactivity on cartilage in vitro. The changes in inhibitory bioactivity observed in diabetic serum are associated with similar changes in serum concentrations of BP-28. We propose that BP-28 is one of the IGF-I inhibitors observed in diabetic serum and that it may play a role in retarded growth and delayed puberty often seen in the adolescent diabetic.     

INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS IN FOLLICULAR FLUID FROM NORMAL DOMINANT AND COHORT FOLLICLES, POLYCYSTIC AND MULTICYSTIC OVARIES

There is now considerable evidence that the insulin-like growth factors (IGFs) play an important role in the human ovary. It has also recently become apparent that the physiological activity of the IGFs is modulated by a number of specific binding proteins (IGFBPs). In order to understand the role of the IGFs in ovarian physiology, the presence and functions of these IGFBPs will need to be characterized. As an initial step towards this we have investigated the presence of the various binding proteins by Western ligand blotting and have measured the levels of one of them, IGFBP-1, in follicular fluid (FF) obtained from unstimulated dominant and cohort follicles in 19 normal women and in eight patients with polycystic and one with multicystic ovaries. In normal women, IGFBP-1 levels in dominant follicles were similar to matched serum levels but were significantly lower in cohort follicles. IGFBP-1 levels correlated with FF-volume (r = 0.58, P less than 0.001) and with paired serum levels (r = 0.63, P less than 0.001). In post-LH surge dominant follicles this relationship with serum levels no longer held and in three out of nine subjects FF levels were higher than in serum. Thus IGFBP-1 in normal human FF appears to be partly derived from the circulation but with additional local production in the larger developing dominant follicles. Western ligand blotting revealed five IGF-binding proteins in FF running parallel with those identified in serum, suggesting that the IGFBP species previously identified in serum may also be present in FF. The two bands in positions corresponding to the components of the large (150kDa) binding complex were, as in serum, the predominant forms and in most FF samples these were even more prominent than in the accompanying serum sample. This contrasts with previous studies in lymph which suggested that the 150kDa complex was largely retained in the circulation. All three small IGFBPs varied considerably between FF samples even within an individual; each IGFBP varied independently of the other IGFBPs. Our results demonstrate that at least four discrete IGFBPs are present in FF and suggest that each may be produced independently within the ovary.     

RESPONSES TO ANALOGUES OF GROWTH HORMONE-RELEASING HORMONE IN NORMAL SUBJECTS, AND IN GROWTH-HORMONE DEFICIENT CHILDREN AND YOUNG ADULTS

Three analogues of growth hormone-releasing hormone (GHRH) have been compared in normal subjects. GHRH(1-29)NH2 is equipotent to GHRH(1-40); increasing doses from 10-200 micrograms per subject augments the duration of stimulated growth hormone (GH) release, but the peak serum GH shows only a poor correlation with dose. The derivative D-Ala2-GHRH(1-29)NH2 is no more potent than the unsubstituted GHRH(1-29)NH2. In 20 children and young adults with growth hormone deficiency by conventional criteria, eight showed normal or only slightly subnormal peak serum GH responses to GHRH(1-40) or GHRH(1-29)NH2. These included two patients with tumours of the hypothalamus, as well as six with idiopathic isolated growth hormone deficiency or panhypopituitarism. A poor response to GHRH was generally seen in patients on long-term GH therapy. Priming with GHRH, in either a single bolus or a continuous infusion, did not increase the GH response to GHRH. It is concluded that GHRH(1-29)NH2 is a useful analogue in the testing of GH reserve in patients with growth hormone deficiency, and has considerable potential for long-term therapy.     

INSULIN-LIKE GROWTH FACTOR-1: A PROGNOSTIC FACTOR OF KNEE OSTEOARTHRITIS

During a population survey in 1975–1978 persons with radiologicalosteoarthritis (ROA) of the knee were identified. After 12 yearsa follow-up study was conducted to study the effect of circulatinginsulin-like growth factor-1 (IGF-1) on cartilage loss, osteophytegrowth and overall progression in 141 persons with confirmedROA of the knee. The outcome measures were scored by comparingthe radiographs taken at baseline and at follow-up. Insulin-likegrowth factor-1 was measured by radioimmunoassay in serum takenat follow-up and in 79% of the baseline sera. After adjustingfor age, gender and body mass index at baseline, IGF-1 concentrationat follow-up was related to osteophyte growth and overall progression.The adjusted odds ratio of the highest vs the lowest tertilewas 2.96 (95% Cl: 1.15–7.60) for osteophyte growth and2.58 (1.01–6.60) for overall progression. No clear relationshipwas found with cartilage loss. These results were confirmedwhen baseline IGF-1 was studied. We conclude that the circulatingIGF-1 concentration has an effect on the course of knee OA byinfluencing osteophyte formation but a preventive effect oncartilage loss could not be shown. KEY WORDS: Insulin-like growth factor-1, Osteoarthritis, Knee, Follow-up study, Prognosis, Longitudinal study, Epidemiology, General population      

大肠癌组织中表皮生长因子及受体的检测

本文应用免疫组化ABC法检测52例大肠癌和18例正常结肠组织中表皮生长因子（EGF）和表皮生长因子受体（EGF－R）的表达状况。正常组织中EGF阳性率22．2％，EGF－R阳性率16．7％，大肠癌EGF阳性率67．3％，EGF－R阳性率61．5％，二者均明显高于正常对照组织，（P＜0．05）。EGF和EGF－R阳性率与患者年龄，性别及肿瘤部位无明显相关，但随着肿瘤浸润度的加深，EGF与EGF－R的阳性率逐渐增高，有淋巴结转移者二者阳性率高于淋转阴性者，特别是EGF与EGF－R双阳者中有82．6％为进展期大肠癌，另发现低分化大肠癌中EGF和EGF－R阳性率明显低于中高分化癌。本文结果提示：部分大肠癌存在EGF或EGF－R的过度表达；EGF与EGF－R的过度表达与肿瘤润度及淋巴转移有关，其检测可作为诊断肿瘤恶性程度的一项辅助指标，部分正常大肠粘膜组织中也有少量EGF或EGF－R表达。     

EFFECT OF ANDROGENS ON PLASMA SOMATOMEDIN-C/INSULIN-LIKE GROWTH FACTOR I RESPONSES TO GROWTH HORMONE

In search of the mechanism for the relatively high plasma somatomedin-C (Sm-C) concentrations in pubertal boys and girls, we have measured the plasma Sm-C responses to exogenous growth hormone (GH) in prepubertal hypopituitary boys before and after testosterone administration. Sm-C responses were determined in 5 hypopituitary boys (9–14 years of age) who were given two successive injections of GH (0·1 U/kg) 48 h apart. Eight days later, after administering 200 mg testosterone IM, their Sm-C responses to the same GH challenge were reassessed. There were no significant differences between the pre-testosterone Sm-C response to GH and the post-testosterone response, despite evidence for reductions in 24 h urinary nitrogen excretion and serum urea nitrogen concentrations in response to testosterone. The results provide no evidence that androgen augments the effect of GH to raise plasma Sm-C during puberty, or that androgen has a direct stimulatory effect on Sm-C production. By inference and from published reports, it appears more likely that a sex hormone-stimulated increase in GH secretion is responsible for the increased Sm-C observed during puberty.     

NYCTOHEMERAL SECRETION OF GROWTH HORMONE IN NORMAL CHILDREN OF SHORT STATURE AND IN CHILDREN WITH HYPOPITUITARISM AND INTRAUTERINE GROWTH RETARDATION

A continuous blood sampling technique has been used to monitor human growth hormone (GH) during sleep in fourteen normal short children (age range 6.5-15.0 years), twelve hypopituitary children (2.8-17.3 years), three children with psychosocial GH deficiency (4.0-13.0 years), and three children with intrauterine growth retardation (9.5-11.3 years). The mean GH level of a 5 h sleep period (22.30-03.30 hours) was used to represent the GH response to sleep. The GH response to insulin induced hypoglycaemia (IST) was also determined. In normal short children there was a significant relationship between 5 h mean GH levels and chronological age. The curve defining this relationship was similar to the third centile linear growth velocity curve. The 5 h mean GH levels of the hypopituitary and psychosocial GH deficiency children were more than 2 SD below the age related mean established for normal short children. The children with intrauterine growth retardation demonstrated values which were more than 2 SD above the age related mean.