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Biomedical subjects

K K Ho

Publications and source records attributed to K K Ho.

At least 91 records · Page 5Linked to original sources
PubMed1997

Multivessel Palmaz-Schatz stenting: early results and one-year outcome.

OBJECTIVES: To determine whether the benefits outlined in Background might extend to patients with multivessel disease, we examined the short- and long-term outcome of multivessel Palmaz-Schatz stenting. BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) has become the dominant treatment for most patients with single-vessel coronary artery disease and has emerged as an alternative treatment for selected patients with multivessel coronary artery disease. Although multivessel angioplasty has excellent early results and low procedural complication rates, long-term outcome is tempered by the frequent need for repeat revascularization. In patients with single-vessel coronary artery disease, Palmaz-Schatz stenting has been shown to have a higher success rate and a lower restenosis rate than conventional PTCA. METHODS: A total of 103 patients (mean age 64 +/- 11 years, 78 men and 25 women) underwent stenting of 212 vessels (saphenous vein graft [53%], left anterior descending coronary artery [20%], left circumflex artery [12%] and right coronary artery [15%]). In 88 patients (85%), multivessel stenting was performed during the same procedure, whereas the remaining 15 patients (15%) had staged multivessel stenting within 1 week of the index stent. Stenting involved only native coronary arteries in 33 patients and only vein grafts in 51 patients. RESULTS: Angiographic success was achieved in 102 patients (99%). Major complications developed in three patients: one patient died, and two patients had Q wave myocardial infarction, with no emergency coronary artery bypass graft surgery or stent thrombosis. Eleven additional patients (11%) developed non-Q wave myocardial infarction, and nine patients (9%) had local vascular complications requiring surgical repair. Clinical follow-up was available in all patients at a mean of 13 +/- 8 months. At 1 year, survival was 98%, with an event-free survival rate of 80%, reflecting predominantly repeat revascularization (17% overall, with 9% target site revascularization). Multivessel native coronary stenting resulted in a higher event-free survival rate and a lower probability of repeat revascularization than did multivessel saphenous vein graft stenting. CONCLUSIONS: In selected patients, multivessel Palmaz-Schatz stenting is technically feasible and carries both excellent early results and favorable 1-year clinical outcome.

Aged↗
PubMed1997

Arthritis susceptibility in mice expressing human type II collagen in cartilage.

Collagen type II (CII) induced arthritis (CIA) in mice is an experimental model for rheumatoid arthritis. Induction with non-self (e.g. human) CII induces severe arthritis whereas the mice are less susceptible to induction with self CII (i.e. mouse). To analyse whether an autoimmune response to human CII can develop and is pathogenic the authors have established transgenic mice expressing human CII in cartilage and backcrossed them into two different gene backgrounds susceptible to CIA (DBA/1 and C3H.Q). The transgenic human CII expression was restricted to cartilage and did not disturb cartilage morphology or lead to chondrodystrophy. In addition, development of stress-induced arthritis was not affected by the transgene. The cartilage specific expression of human CII reduced, but did not eliminate, the susceptibility to CIA irrespective of the species source (human, bovine, chick, rat) of CII used for immunization. A common denominator between these heterologous CII in comparison with mouse CII is the previously defined CII 256-270 epitope. An expression level dependent T-cell tolerance was seen in this epitope as well as to the entire CII. However, all human transgenic mouse lines could still mount significant autoreactive T- and B-cell responses. Approximately 10% of the transgenic mice developed arthritis after immunization with human CII. These findings show, therefore, that cartilage-located human CII induce tolerance but can nevertheless be a target for development of arthritis.

Animals↗
PubMed1997

Stimulation of mitochondrial fatty acid oxidation by growth hormone in human fibroblasts.

In vivo administration of GH induces lipolysis and lipid oxidation. However, it is not clear whether the stimulation of lipid oxidation is a direct effect of GH or is driven by increased substrate supply secondary to lipolysis. An in vitro bioassay has been established for assessing beta-oxidation of fatty acids in mitochondria, based on the measurement of conversion of tritiated palmitic acid to 5H2O by fibroblasts in culture. We have modified this assay to investigate whether GH stimulates fatty acid oxidation. GH stimulated oxidation of palmitic acid maximally by 26.7 +/- 2.5% (mean +/- SEM; P < 0.0001). The stimulation was biphasic, with the oxidation rate increasing with increasing GH concentration to a peak response at 1.5 nmol/L and declining to a level not significantly different from control thereafter. Insulin-like growth factor-I at concentrations of up to 250 nmol/L had no significant effect on fatty acid oxidation. GH-binding protein attenuated the effect of GH. An anti-GH receptor (GHR) antibody (MAb263), which dimerizes the receptor and induces GH-like biological actions, significantly stimulated fatty acid oxidation. Another anti-GHR antibody (MAb5), which prevents receptor dimerization, suppressed GH action. In summary, GH directly stimulated fatty acid oxidation, an action not mediated by insulin-like growth factor-I. Dimerization of GHRs was necessary for this effect. This bioassay is a practical tool for studying the regulatory effects of GH on lipid oxidation.

Antibodies, Monoclonal↗
PubMed1997

Urolume prostatic stents for urinary retention due to benign prostatic hyperplasia in patients with high medical risks.

A retrospective study was conducted to evaluate the efficacy of using urolume prostatic stents in patients who have developed urinary retention due to benign prostatic hyperplasia but who are medically unfit for conventional transurethral resection of the prostate. From April 1995 through May 1996, 12 patients were studied (mean age, 80 years; range, 72-92 years). Pre-operative assessment pointed to major risk due to an underlying medical condition. Flexible cystoscopy and video-urodynamcis were performed to assess the detrusor function and to ascertain if prostatic obstruction was the cause of retention. After insertion of the prostatic stent, 11 patients managed to void on recovery from the anaesthesia and remained catheter-free during a mean follow up period of seven months (range, 2-18 months). There was no operative morbidity or mortality. Urolume prostatic stents represent a viable option for elderly patients with significant medical risks who have urinary retention. Pre-operative urodynamics are essential to identify appropriate candidates.

Journal Article↗
PubMed1997

Highly successful long-term outcome of kidney transplantation in Chinese recipients: an enhancing race effect?

We report on 352 cadaveric kidney transplants and 294 living related transplants performed over a 25-yr period among the Chinese population of Hong Kong. There is a marked preference for transplanting male patients, especially from living donors, and we argue that this represents a cultural phenomenon within the Chinese population. The 10-yr graft survivals for related and cadaveric transplants are 86.2% and 67.4%, respectively. These figures are appreciably higher than corresponding figures in Caucasian populations. We show beneficial effects of using cyclosporin A, minimizing the cold ischemia time and avoiding very young and very old donors. There is a clear benefit of transplanting kidneys with zero or one mismatched HLA antigen against the recipient but no stepwise decrease in outcome as the number of mismatched antigens increases. There is close concordance between the outcome of living related grafts with zero, one, and two mismatched haplotypes against the recipient and no observable benefit of haplotype matching. We show that Chinese renal transplant recipients in other centers also have better long-term graft outcome than Caucasians, both for cadaveric and living related transplants. We draw attention to the existence of a detrimental "race effect" in other studies when Black recipients are compared with Caucasians and consider whether an enhancing race effect exists for Chinese or whether the better outcome reflects different underlying diseases in Chinese.

Actuarial Analysis↗
PubMed1997

Dialysis adequacy of Asian patients receiving small volume continuous ambulatory peritoneal dialysis.

The usage of three x 2 liter daily exchanges is adopted as the standard CAPD regime in Hong Kong over the last 10 years due to budgetary constraint. This dialysis prescription is considered suboptimal in Western standard. However, the necessity of maintaining Kt/V > 1.7 for CAPD dialysis adequacy is not unanimously agreed. We performed a cross-sectional study of 117 patients on CAPD. Seventy-eight percent of our patients had 3 x 2 liter daily exchange while the rest had 4 daily exchanges. Fifteen percent of patients were diabetic. Patients with Kt/V < 1.7 were similar to those with Kt/V > 1.7 in age, duration of CAPD, BUN, plasma creatinine, albumin, peritonitis rate, and incidence of hypertension. Patients with Kt/V > or = 1.7 had higher hemoglobin, higher nPCR, more residual renal function; and more of them received 4 daily exchanges. Their peritoneal permeability did not differ. Their employment and rehabilitation status was also similar. Our 5-year survival was 79% despite a lower Kt/V. Notably, the protein catabolic rate of our patients was higher than that in Western patients. This is likely due to dietary difference. Our study suggests small-volume dialysis may be acceptable in Asian population with smaller body size given the financial constraint.

Adult↗
PubMed1996

4-[4-[(2-Hydroxybenzoyl)amino]phenyl]butyric acid as a novel oral delivery agent for recombinant human growth hormone.

A series of N-acetylated, non-alpha, aromatic amino acids was prepared and shown to promote the absorption of recombinant human growth hormone (rhGH) from the gastrointestinal tract. Seventy compounds in this family were tested in vivo in rats. Of the compounds tested, 4-[4-[(2-hydroxybenzoyl)amino]phenyl]butyric acid was identified as a preclinical candidate and was used to demonstrate the oral delivery of rhGH in primates. A significant positive correlation was found between the relative log k' of the delivery agents, as determined by HPLC on an immobilized artificial membrane (IAM) column, and serum rhGH concentrations following oral or colonic dosing in rats. Structure-activity relationships have also been developed on the basis of electronic effects and hydrogen-bonding characteristics of the aromatic amide substituents.

Administration, Oral↗
PubMed1996

Enhanced antiopiate activity and enzyme resistance in a peptidomimetic of FMRFamide containing E-2,3-methanomethionine and E-2,3-methanophenylalanine.

FMRFamide is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. Peptidomimetics of FMRFamide substituted with conformationally constrained stereoisomers of Z-2,3-methanomethionine or E-2,3-methanomethionine precipitated abstinence syndrome far more potently than FMRFamide itself. The current study determined the effect on antiopiate potency of an additional rigid substitution. A peptidomimetic containing a stereoisomer of E-2,3-methanomethionine was compared with a peptidomimetic additionally substituted at the C-terminal with E-2,3-methanophenylalanine. Morphine abstinence signs were observed after varying doses (0.125-25.0 micrograms) of these two peptidomimetics were injected into the third ventricle of morphine-dependent rats. The peptidomimetic containing both rigid substitutions was far more potent than the peptidomimetic of FMRFamide containing methanomethionine alone. The increased potency appears to be related to enzyme resistance rather than receptor affinity.

Amino Acid Sequence↗
PubMed1996

Impaired growth hormone secretion and increased growth hormone-binding protein levels in subfertile males.

OBJECTIVE: To evaluate GH secretion in subfertile males. DESIGN: Comparing GH secretion to a GH stimulation test in two different patient groups and in a control group. PATIENTS: Nine oligozoospermic patients, nine asthenozoospermic patients, and nine age- and body mass index-matched fertile males with normal spermograms. INTERVENTION: All subjects underwent an IV arginine GH stimulation test. MAIN OUTCOME MEASURES: Serum levels of FSH, LH, PRL, E2, T, insulin-like growth factor I (IGF-I), and GH-binding protein were measured. RESULTS: Basal levels of GH were similar in all three groups and serum GH increased in all groups after arginine. However, there was a significant difference between the two patient groups and the control group characterized by an impaired GH response in the subfertile patients. Serum FSH and serum GH-binding protein were significantly higher in the patient groups compared with the controls. Serum LH, PRL, T, E2, and IGF-I were similar in all three groups. CONCLUSIONS: This study demonstrates that subfertile men may suffer from relative GH insufficiency, which could have therapeutical implications.

Adult↗
PubMed1996

Growth hormone treatment of subfertile males.

OBJECTIVE: To study spermatogenesis and sperm motility during GH therapy in infertile men. DESIGN: Prospective open study. Each patient was treated with GH for 12 weeks and followed for a total of 36 weeks with sampling of blood and semen. SETTING: Outpatients studied at a clinical research unit of a university hospital. PATIENTS: Nine oligozoospermic (<5 x 10(6) sperm/mL) males and nine asthenozoospermic (percentage motile sperm <30 and >15 x 10(6) sperm/mL) males. The patient groups had a significantly lower GH response to an arginine GH stimulation test as compared with a control group. RESULTS: Serum insulin-like growth factor I (IGF-I) and serum IGF-binding protein 3 (IGFBP-3) levels increased significantly during GH treatment, as did seminal IGF-I. Serum E2, T, PRL, FSH, LH, and GH-binding protein were unchanged during the study. Sperm motility was increased significantly during GH treatment in both patient groups. There was no difference in sperm count during the treatment. There were three pregnancies in the nine couples from the asthenozoospermic group and no pregnancies in the oligozoospermic group. CONCLUSION: The biologic and clinical results in this study encourage the initiation of double-blind, placebo-controlled trials.

Adult↗
PubMed1996

A simple, rapid immunometric assay for determination of functional and growth hormone-occupied growth hormone-binding protein in human serum.

We present a sensitive time-resolved fluorometric immunofunctional assay (TR-FIA) for direct quantitation of functional growth hormone-binding protein (GHBP), using an immunoassay kit for growth hormone (GH-DELFIA). In addition to the immobilized GH antibody, one monoclonal antibody against GHBP was used. This anti-GHBP was labelled with the chelate of europium. The assay was performed in one step. The detection limit for GHBP was 0.044 nmol L-1 (NBS + 3 SD). The calibration curve was linear in the interval 0.11-8.03 nmol L-1. Average intra-assay coefficient of variation (CV) was 3.44%. Average interassay CV at GHBP concentrations 0.563 nmol L-1 and 1.40 nmol L-1 were 12% and 6.3% respectively. Analytical recovery in serum ranged from 76% to 127% with a mean of 101 +/- 3.6%. Serum GHBP in 102 normal subjects ranged from 0.513 to 3.772 nmol L-1 and was positively related to body mass index (P < 0.001). In growth hormone-deficient sera GHBP was higher than in control subjects (1.751 +/- 0.179 nmol L-1 and 1.257 +/- 0.140 nmol L-1 respectively, P < 0.001). Acromegalic patients had lower levels of GHBP than controls (0.946 +/- 0.251 and 1.234 +/- 0.144 nmol L-1 respectively, P = 0.005). This assay also allowed detection of GH-complexed GHBP in serum. These results were in agreement with theoretical values calculated from the measured GH and the functional GHBP concentrations. Results were compared with data obtained by a recently reported, validated ligand immunofunctional assay (LIFA), which is fundamentally different. There was a significant linear relationship between the results from the two assays (r = 0.89, P = 0.001). The slope of the regression line was 0.65. In conclusion, this new convenient GHBP TR-FIA provides a sensitive and precise method for detecting total GHBP as well as complexed GHBP in human serum, and allows easy processing of large numbers of samples.

Acromegaly↗
PubMed1996

Sex steroid regulation of growth hormone secretion and action.

Evidence that oestrogen is involved in the regulation of the somatotrophic axis in adult humans is provided by the observations that mean growth hormone (GH) levels are higher in women than men, that the fall in GH and insulin-like growth factor-1 (IGF-1) with aging are correlated to oestradiol levels and that oestrogen increases the GH responses to provocative stimuli. To investigate whether oestrogen modulates GH secretion and action in adult life, we studied the impact of oestrogen replacement on circulating GH and IGF-1 levels in postmenopausal women. Since the liver is the major source of circulating IGF-1 and the oral route of oestrogen delivery causes nonphysiologic effects on hepatic proteins, we compared the effects of oral and transdermal routes of delivery. Oral ethinyl oestradiol administration resulted in a significant fall in mean IGF-1 levels and a threefold increase in mean 24-hour GH. Transdermal administration of 17 beta-oestradiol resulted in a slight increase in serum IGF-1 but no change in mean 24-hour GH levels. To determine whether differences in oestrogen type rather than in the route of delivery caused the different effects on the GH/IGF-1 axis, we compared the effects of three oral oestrogen formulations. Ethinyl oestradiol, conjugated equine oestrogen and oestradiol valerate each induced a fall in IGF-1 and a rise in mean 24-hour GH levels in postmenopausal women. To determine the significance of oestrogen-induced changes on IGF-1, we studied effects on markers of connective and bone tissue activity. We found that propeptide concentrations of type III and type I collagen, and osteocalcin rose and fell in parallel with IGF-1 during oral or transdermal oestrogen therapy. Oestrogen causes distinct, route-dependent effects on the somatotrophic axis. The dissociation of the GH/IGF-1 axis by the oral route is likely to arise from impaired hepatic IGF-1 production which causes increased GH secretion through reduced feedback inhibition. Oestrogen treatment may have longer-term metabolic effects on hypogonadal women exerted through effects on the somatotrophic axis.

Adult↗
PubMed1996

Insulin-like growth factor I and insulin down-regulate growth hormone (GH) receptors in rat osteoblasts: evidence for a peripheral feedback loop regulating GH action.

The anabolic actions of GH are mediated by the production of insulin-like growth factor I (IGF-I) from the liver and by local production of IGF-I in extrahepatic tissues. Insulin facilitates the hepatic production of IGF-I by up-regulating GH receptors (GHRs) in the liver and augmenting the IGF-I response to GH. Although GHRs have also been identified in extrahepatic tissues that produce IGF-I, the possibility that IGF-I and insulin might partake in GHR regulation, thereby modulating the effects of GH locally has not received detailed study. The aim of this study was to investigate whether IGF-I and insulin are involved in the local regulation of GHRs, using osteoblasts as a model of GH-responsive extrahepatic tissues. We have used UMR106.06, a well differentiated rat osteoblast-like cell line that expresses GHRs and exhibits a mitogenic response to GH. IGF-I and insulin (0-10 nM) increased cell number and reduced [125I]GH binding in a concentration-dependent manner, with ED50 values of 0.8 and 0.3 nM, respectively. Although IGF-I increased cell number maximally by 36.9 +/- 1.2% (mean +/- SE) above the control value and insulin by 104.8 +/- 5.7% (P < 0.001), they decreased GH binding to 47.0 +/- 9.3% (P < 0.01) and 29.8 +/- 8.7% of the control value (P < 0.001), respectively. Scatchard analysis revealed that the down-regulation of GH binding was attributed to reduced receptor numbers and not binding affinity. The effects of IGF-I and insulin at submaximal concentrations were additive, although the combined effects did not exceed the maximal effect of either growth factor alone. Addition of an anti-IGF-I receptor antibody (alpha IR3) reversed the inhibition of GH binding induced by IGF-I, but not that caused by insulin; similarly, an antiinsulin receptor antibody (29B4) attenuated the inhibitory effect of insulin only. Addition of alpha IR3 alone or an ant-IGF-I antibody (Sm1.2) decreased cell number and increased GH binding in a concentration-dependent mode. GH at 1.5 nM significant increased cell number by 19.3 +/- 2.4% above the control level (P < 0.01), an increase that was reversed by alpha IR3. GH increased GH binding by 32.4 +/- 7.2% (P < 0.05) in cells treated with alpha IR3 to remove the secondary effect of IGF-I. In summary, IGF-I and insulin acted via specific receptors to stimulate cell proliferation and down-regulate GHRs in osteoblasts. GH stimulated cell proliferation, an action mediated by local production of IGF-I, and GH enhanced its own binding. The collective data suggest the presence of a peripheral negative feedback loop that allows IGF-I to limit locally the response of extrahepatic tissues to circulating GH.

Analysis of Variance↗
PubMed1996

Short-term growth hormone (GH) treatment of GH-deficient adults increases body sodium and extracellular water, but not blood pressure.

Initiation of GH treatment in adults is frequently complicated by the development of symptomatic fluid retention. To investigate the mechanism and extent of fluid retention that occurs with dosages of GH used in the treatment of GH-deficient adults, we conducted a double blind study in which seven GH-deficient patients (aged 24-74 yr) each received in random order daily sc injections of placebo, a physiological dose of GH (0.04 U/kg, low dose), and a supraphysiological dose of GH (0.08 U/kg, high dose) for 7 days, separated by 21-day washout periods. On the seventh day, measurements were made of serum insulin-like growth factor I, body weight, exchangeable sodium, plasma volume, angiotensinogen, PRA, aldosterone, atrial natriuretic peptide (ANP), and mean 24-h ambulatory heart rate and blood pressure. GH significantly increased mean insulin-like growth factor I levels from 105 +/- 11 to 304 +/- 45 micrograms/L during low dose treatment (P = 0.006) and 400 +/- 76 micrograms/L during high dose treatment (P = 0.004). High dose GH caused a 1.2 +/- 0.3 kg increase in body weight (P = 0.01) and a 193 +/- 65 mmol increase in exchangeable sodium (P = 0.008). Low dose GH had a lesser effect, with no significant increase in body weight, but an increase in exchangeable sodium of 113 +/- 37 mmol (P = 0.02). Plasma volume was not significantly affected by GH treatment. Mean supine angiotensinogen levels were significantly higher during both GH treatments compared to placebo (low dose, P = 0.017; high dose, P = 0.028) as were mean supine PRA levels (low dose, P = 0.0002; high dose, P = 0.0025). Supine angiotensin II, aldosterone, and ANP levels were not significantly affected by GH treatment. There was no significant change from placebo in any of the sodium-regulating hormones in the erect posture. The mean 24-h heart rate was significantly higher during low dose (82 +/- 2 beats/min; P = 0.0001) and high dose (88 +/- 3 beats/min; P = 0.0001) GH treatment than during placebo (67 +/- 3 beats/min). However, no significant change in mean 24-h systolic or diastolic blood pressure was observed. In summary, acute GH administration using doses currently employed in treating adults causes a dose-related increase in body weight and body sodium, but no associated increase in blood pressure. We conclude that 1) sodium retention is a physiological effect of GH, but does not cause an acute rise in blood pressure; and 2) the mechanism of sodium and fluid retention is not primarily due to enhanced aldosterone secretion or inhibition of ANP release, but more likely to a direct renal tubular effect.

Adult↗
PubMed1996

Serum growth hormone-binding protein in obesity: effect of a short-term, very low calorie diet and diet-induced weight loss.

GH-binding protein (GHBP) is increased in obesity. It is not known whether the increase in GHBP is reversible with weight loss or modulated by acute changes in nutritional intake. To address these questions, we measured GHBP in 18 obese subjects [body mass index (BMI), 40.9 +/- 1.1 kg/m2 (mean +/-SEM)] before and after an average weight loss of 30.3 +/- 4.6 kg and in 18 age- and sex matched normal subjects (BMI, 23.0 +/- 0.4 kg/m2) and studied the effects of a very low calorie diet over 4 days in 5 normal subjects and a subgroup of obese subjects before (n = 6) and after (n = 5) weight loss. GHBP was elevated in the obese subjects compared to levels in age- and sex-matched normal controls (1.48 +/- 0.1 vs. 0.53 +/- 0.1 nmol/L; P < 0.0001). GHBP was positively correlated to BMI and waist circumference (r = 0.71; P < 0.00001 and r = 0.73; P < 0.00001, respectively). In addition, GHBP was positively correlated to insulin as well as proinsulin levels (r = 0.60; P < 0.001 and r = 0.55; P < 0.001, respectively). After diet-induced massive weight loss, GHBP levels were restored to normal in obese subjects (BMI, 27.8 +/- 1.4 kg/m2). Multiple stepwise regression analysis revealed that changes in waist circumference and abdominal sagittal diameter during weight loss were the major determinants of and accounted for 54% of the fall in GHBP levels. Neither insulin nor proinsulin was an independent predictor. No changes were observed in GHBP in normal, obese, or reduced weight obese subjects after 4 days of a very low calorie diet, although mean insulin levels fell significantly in the normal subgroup as well as in the obese subgroup studied after weight loss. In summary, GHBP levels are elevated in obesity, are restored to normal by massive weight loss, and are unaffected by short term hypocaloric feeding. We conclude that GHBP may be regulated by the same or closely related factors that regulate fat mass and abdominal fat mass in particular, but not by insulin or acute changes in nutrition.

Adult↗
PubMed1996

A highly sensitive growth hormone (GH) enzyme-linked immunosorbent assay uncovers increased contribution of a tonic mode of GH secretion in adults with organic GH deficiency.

The limited sensitivity of conventional GH assays has impeded a better understanding of the pathophysiology of GH secretion. In normal subjects, interpulse GH levels often fall below assay sensitivity, making it unclear whether secretion stops or is maintained at a tonic level below assay detectability. In patients with severe organic GH deficiency (GHD), GH levels are mostly undetectable. Using an ultrasensitive GH enzyme-linked immunosorbent assay to measure 24-h integrated GH concentrations, we recently provided evidence that these patients secrete low, but measurable, amounts of GH. In this report, we apply the same assay to characterize and compare 24-h GH profiles obtained by 20-min sampling in 10 subjects with organic GHD and 10 normal subjects matched for age, sex, and body mass index. With deconvolution analysis, which provides estimates of GH secretion and half-life, our aim was to determine 1) whether normal GH secretion is exclusively pulsatile, 2) how GH is secreted in subjects with organic GHD, and 3) the attributes of GH secretion that determine circulating insulin-like growth factor I (IGF-I) levels. All samples, including nadirs, from GHD subjects were well within the assay detection limit (1 ng/L). Peak 24-h GH levels in GHD subjects were lower and did not overlap those in the normal subjects. Nadir GH concentrations were significantly lower in GHD subjects (14 +/- 5 vs. 43 +/- 9 ng/L; P = 0.008), but the range overlapped that of normal subjects. Endogenous GH half-life did not differ significantly between the two groups. Normal subjects secreted GH in a mixed pulsatile and tonic mode, with pulsatile secretion accounting for 93 +/- 2% of the total production. Total daily GH production in GHD was approximately 5% of the production in matched normal subjects. This difference resulted from a greater reduction in the pulsatile (by 96%) than in the tonic (by 47%) component, so that the fractional daily contribution by tonic GH release in GHD subjects was markedly greater. There was a significant relationship between pulsatile GH secretion and serum IGF-I levels for the two groups combined. In summary, 1) peak, but not nadir, GH levels were completely segregated between GHD and normal subjects; and 2) although normal subjects secrete GH in a tonic and pulsatile mode, both modes are reduced in organic GHD, with a proportionately greater reduction in pulsatile secretion. We conclude that 1) nadir GH levels are not sufficiently discriminatory to be useful for the diagnosis of GH deficiency; 2) normal GH profiles arise from a mixed pattern of tonic and pulsatile secretion, whereas reduced GH secretion in organic GHD arises primarily from a marked diminution in the amount of pulsatile GH release; and 3) pulsatile GH release is a significant regulator of the IGF-I level in normal and GHD subjects.

Adult↗
PubMed1996

Metabolic actions of growth hormone in man.

GH continues to be produced after the cessation of childhood growth and is the most abundant pituitary hormone in the adult pituitary. There is strong evidence that GH continues to exert significant biological effects on body metabolism in adult humans. The actions of GH may be direct or indirectly mediated by IGF-1. The direct actions of GH impart major effects on glucose, lipid and sodium homeostasis. GH administration causes hyperinsulinaemia and impairs the ability of insulin to suppress hepatic glucose production and to stimulate glucose uptake and oxidation. GH enhances fat utilisation by stimulating lipolysis and fat oxidation. The significance of these effects is reflected in the finding of increased adiposity in GH deficiency (GHD) and reduced fat mass in acromegaly. GH causes sodium retention which occurs in part through activation of the renin-angiotensin system. Extracellular water volume is diminished in GHD and increased in relation to the extent of GH excess in acromegaly. Lean body mass is reduced in GHD and restored by GH treatment. The anabolic actions of GH are mediated by IGF-1. Studies of whole body protein metabolism show that this occurs through the stimulation of protein synthesis, reduction in protein oxidation but not inhibition of protein breakdown. GH plays an important role in the regulation of substrate metabolism and body composition in man.

Adult↗