Parthenogenetic chimaerism/mosaicism with a Silver-Russell syndrome-like phenotype.

INTRODUCTION: We report a 34-year-old Japanese female with a Silver-Russell syndrome (SRS)-like phenotype and a mosaic Turner syndrome karyotype (45,X/46,XX). METHODS/RESULTS: Molecular studies including methylation analysis of 17 differentially methylated regions (DMRs) on the autosomes and the XIST-DMR on the X chromosome and genome-wide microsatellite analysis for 96 autosomal loci and 30 X chromosomal loci revealed that the 46,XX cell lineage was accompanied by maternal uniparental isodisomy for all chromosomes (upid(AC)mat), whereas the 45,X cell lineage was associated with biparentally derived autosomes and a maternally derived X chromosome. The frequency of the 46,XX upid(AC)mat cells was calculated as 84% in leukocytes, 56% in salivary cells, and 18% in buccal epithelial cells. DISCUSSION: The results imply that a parthenogenetic activation took place around the time of fertilisation of a sperm missing a sex chromosome, resulting in the generation of the upid(AC)mat 46,XX cell lineage by endoreplication of one blastomere containing a female pronucleus and the 45,X cell lineage by union of male and female pronuclei. It is likely that the extent of overall (epi)genetic aberrations exceeded the threshold level for the development of SRS phenotype, but not for the occurrence of other imprinting disorders or recessive Mendelian disorders.

Thyroid hormone modulation of the hypothalamic growth hormone (GH)-releasing factor-pituitary GH axis in the rat.

Both thyroid hormone and hypothalamic growth hormone (GH)-releasing factor (GRF) facilitate pituitary somatotroph function. However, the pathophysiological role of thyroid hormone in GRF secretion is less well understood. Thyrotoxicosis, induced by administration of thyroxine (T4) in rats, inhibited both pituitary GH levels and immunoreactive GRF secretion from incubated hypothalamus. At the highest dose of T4 given for 12 d, GRF secretion and pituitary GH decreased by 50 and 39%, respectively. Hypothyroidism induced by thyroidectomy (Tx) enhanced GRF secretion approximately twofold while depleting pituitary GH by greater than 99%. Both of these hypothalamic and pituitary effects were reversed by replacement of T4 but not human GH for 7 or 14 d. Human GH was as potent as T4 in restoring decreased body weight gains or serum insulin-like growth factor-1 levels in Tx rats. These results indicate that at both physiological and pathological concentrations in serum, thyroid hormone acts as an inhibitory modulator of GRF secretion, probably not involving a feedback mechanism through GH. A biphasic effect of thyroid hormone on pituitary GH levels appears to derive from the difference in primary target tissues of hyper- and hypothyroidism, the hypothalamus and the pituitary, respectively.

Effect of pH and lysosomotropic agents on membrane-associated and internalized 125I-iodinated human growth hormone in cultured human lymphocytes: a quantitative biochemical and electron microscopic study.

When 125I-iodinated human GH ([125I]iodo-hGH) interacts with cultured human lymphocytes at 15 C, the reaction is reversible, but at 37 C the reaction becomes less dissociable as a function of incubation time. Acidification of the incubation medium results in rapid ligand dissociation at 15 C, but at 37 C the acid-dissociable component decreases as a function of incubation time. Under conditions where approximately 50% of the ligand is internalized by the cell, 90% is nondissociable. When the 37 C incubation is carried out in the presence of 25 mM NH4Cl, cell-associated radioactivity is increased. Under these conditions approximately 90% of cell-associated radioactivity also is nondissociable. Using quantitative electron microscopic autoradiography, the proportion of [125I]iodo-hGH associated with the plasma membrane and internalized by the cell is indistinguishable in the presence or absence of NH4Cl. Irreversible [125I]iodo-hGH association with cultured human lymphocytes is due to time- and temperature-dependent effects in the plasma membrane of the cell. These effects cannot be distinguished from internalization by acidification. Furthermore, lysosomotropic agents increase cell-associated radioactivity, but the proportion internalized is not increased.

Effect of insulin and nutrition on serum levels of somatomedin A in the rat.

The serum levels of somatomedin A, as measured by radioreceptor assay, were significantly reduced in rats 2 days after the administration of streptozotocin. The mean decrease was 45.4 +/- 2.9% of the initial values. In rats treated with insulin, blood glucose levels and glycosuria decreased, and serum somatomedin A returned to 108.3% +/- 11.7% of the initial values by the sixth day of treatment. In untreated diabetic rats, serum somatomedin A decreased progressively to 23.4 +/- 4.4% 8 days after streptozotocin administration. The total caloric intakes in the treated and nontreated diabetic rats were similar, suggesting that the low levels of somatomedin A in diabetic rats may be due to lack of insulin. A significant correlation was observed between serum somatomedin A values and body weight (r = 0.90) or the urinary glucose (r = -0.84) or blood glucose levels (r = -0.67). When the diabetic insulin-treated rats were fed a low protein diet, there was no increase in serum somatomedin A. Inhibitory factors in serum which interfere in the bioassay for somatomedin had no effect in our radioreceptor assay.

The effect of glucocorticoids on the insulin receptor: an in vivo and in vitro study.

We have studied the effect of glucocorticoid exposure on the insulin receptor of short term cultures of human lymphocytes (IM-9 cells) and the effect of short term administration of these agents to normal volunteers. When cultured human lymphocytes were exposed to 10(-5) M hydrocortisone for 18 h at 37 C, insulin binding increased due to an increase in the number of receptors per cell. The effect had appropriate specificity in terms of concentration and type of steroid used. By contrast, hGH binding to these cells was decreased under similar circumstances of incubation, due to a decrease in the number of hGH receptors per cell. When prednisone (40 mg/day) was given to normal subjects for 3 days, a moderate state of insulin resistance was induced characterized by a modest increase in blood glucose and a more pronounced increase in plasma insulin concentration. Under these circumstances there was no change in tracer insulin binding to peripheral monocytes nor changes in the concentration of insulin necessary to inhibit binding by 50%, the number of receptors per cell or the affinity of the receptor. We conclude that glucocorticoids increase insulin binding in vitro in cultured human lymphocytes but that competing influences in vivo such as increasing circulating insulin concentration, redistribution of cell types in the circulation, and possibly other influences prevent these changes from occurring in circulating monocytes. These findings emphasize the complexity of studying the effects of pharmacological agents on hormone binding.

The relationship between bone turnover and body weight, serum insulin-like growth factor (IGF) I, and serum IGF-binding protein levels in patients with anorexia nervosa.

Malnutrition is one of the risk factors for bone loss in patients with anorexia nervosa (AN). To clarify the effects of nutritional status on bone metabolism, we examined the relationship between serum levels of nutritional indicators [insulin-like growth factor I (IGF-I), IGF-binding protein-2 (IGFBP-2), and IGFBP-3] and markers for bone metabolism [serum osteocalcin and urinary excretion of C-terminal telopeptide of collagen type I (CrossLaps)] in 45 AN out-patients, including 8 severely malnourished patients who required hospitalization and iv hyperalimentation (IVH). Compared to healthy subjects, serum IGF-I and IGFBP-3 were lower, whereas IGFBP-2 was higher in out-patients who had a body mass index (BMI) less than 16.5 kg/m2. In these patients, urinary excretion of CrossLaps, a marker of bone resorption, was higher, whereas serum osteocalcin, a marker of bone formation, was lower than those in control subjects. All of these parameters were normal in patients whose BMI ranged from 16.5-18.5 kg/m2. Serum levels of osteocalcin correlated positively with BMI (r = 0.512; P<0.0001), IGF-I (r = 0.558; P<0.0001), and IGFBP-3 (r = 0.369; P<0.001) in AN out-patients. In the 8 severely malnourished AN patients, serum levels of IGF-I and osteocalcin significantly increased 3 and 7 days, respectively, after the start of a 5-week IVH therapy regimen and reached normal levels within 5 weeks, accompanied by still elevated urinary excretion of CrossLaps. The present study demonstrates that an improvement in nutritional status in AN patients during IVH therapy rapidly increases the serum IGF-I levels, followed by a progressive increase in osteocalcin, suggesting immediate start of bone formation. However, increased bone resorption appears to continue for at least 5 weeks.

Growth hormone (GH) secretory dynamics in a case of acromegalic gigantism associated with hyperprolactinemia: nonpulsatile secretion of GH may induce elevated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels.

We describe a case of pituitary gigantism with low levels of growth hormone (GH), elevated insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 (IGF-BP-3). The patient had characteristic clinical features of gigantism and acromegaly. The basal serum GH levels ranged from 1.2-1.9 micrograms/L, which were considered to be within normal limits. Serum GH response to either insulin-induced hypoglycemia or GH-releasing hormone was blunted. Frequent blood samplings during daytime and at night showed nonpulsatile GH secretion. Serum prolactin, IGF-I and IGF-binding protein-3 levels were elevated. After unsuccessful surgery, bromocryptine treatment normalized serum prolactin without affecting serum GH and IGF-I levels. Combined administration of octreotide and bromocryptine reduced serum GH and IGF-I levels. GH bioactivity as measured by Nb2 cell proliferation assay was within reference range. In the present case, nonpulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-I and IGF-BP-3 and cause clinical acromegalic gigantism.

Demonstration of insulin-like growth factor I in human urine.

Immunoreactive and receptor-reactive insulin-like growth factor I (IGF-I) was demonstrated in human urine. Thirty percent of the IGF-I immunoreactivity in urine was free, and the remainder was a high mol wt form (approximately 43K). Urinary IGF-I was quantitated by RIA after extraction with octadecylsilyl silica cartridges (Sep-Pak C18 cartridge), a method that measures only free IGF-I. The mean urinary immunoreactive IGF-I levels in normal adults (n = 8) and patients with acromegaly (n = 10) or hypopituitarism (n = 9) were 72 +/- 7 (+/- SEM), 225 +/- 34, and 19 +/- 4 pg/mg creatinine, respectively; these mean values were significantly different from one another. The results indicate that IGF-I is present in human urine and that the quantity in urine is altered in patients with GH excess and deficiency.

Serum somatomedin peptides measured by somatomedin A radioreceptor assay in chronic liver disease.

The levels of serum somatomedin peptides were determined with a somatomedin A radioreceptor assay utilizing human placental membranes. Low levels were found in 25 patients with liver cirrhosis and 28 patients with chronic hepatitis with the mean of 0.47 +/- 0.05 and 0.60 +/- 0.04 U/ml, respectively. There was a positive correlation between somatomedin A on one hand and serum albumin, cholinesterase, total cholesterol and thrombotest on the other. There was a negative correlation between somatomedin A and the indocyanine green retention test. These findings confirm earlier results obtained with bioassay.

Properties of human growth hormone polypeptides: purified from pituitary extracts and synthesized in monkey kidney cells and bacteria.

Several forms of human GH (hGH) have been elucidated by extraction of human pituitary and recombinant DNA techniques. In the present study we have characterized five of these hGH polypeptides by gel filtration, RIA, and radioreceptor assays. These include extractable pituitary hGH and its naturally occurring 20K variant. Two hGH polypeptides were produced from naturally occurring human genes in simian kidney cells (SV-hGH 1 and 2) and another preparation was produced from a partially synthesized gene in bacteria (E. coli-hGH). As predicted from their known DNA sequences, naturally occurring pituitary hGH, SV-hGH 1, and E. coli-hGH migrated as a single peak on Sephadex G-100 column and had the same immunological and receptor-binding properties. By contrast, SV-hGH 2 (14 dispersed amino acid substitutions) and the 20K variant (amino acid residues 32-46 deleted from hGH) contained more higher molecular weight components and had diminished immunological and receptor-binding potency. SV-hGH 2 differed from the 20K variant by having even lower immunological potency and containing more of the higher molecular weight component. These variant forms of hGH may provide an explanation for the heterogeneity of both pituitary and plasma hGH.

Characterization of insulin-like growth factor I receptor on human erythrocytes.

[125I]Insulin-like growth factor I (IGF-I) specifically bound to erythrocytes; the binding was saturable, and time and temperature dependent. Steady state binding was reached at 16 h at 4 C, and specific binding averaged 14.3 +/- 0.7% (+/- SEM) at a concentration of 3.6 X 10(9) cells/ml in seven normal subjects. [125I]IGF-I binding to the cells was displaced by unlabeled IGF-I in a dose-dependent manner. Scatchard analysis indicated a linear plot, and Ka and number of binding sites/cell were 1.43 +/- 0.07 X 10(9) M-1 and 20.7 +/- 2.2, respectively. Compared to IGF-I, the relative potencies of multiplication-stimulating activity and insulin for displacing [125I]IGF-I binding were 20% and 1%, respectively. [125I]IGF-I binding to erythrocytes from patients with acromegaly was lower than binding to cells from pituitary dwarfs. An inverse correlation between plasma IGF-I level and the number of IGF-I-binding sites per cell was found (r = -0.75; P less than 0.005). These results demonstrate that [125I]IGF-I binding to erythrocytes can be used for clinical measurement of the IGF-I receptor.

Characteristics of human erythrocyte insulin-like growth factor I receptors.

The scarcity of purified materials has prevented studies of the mechanism of insulin-like growth factor I (IGF-I) action. Recently, an IGF-I analog, Thr59-IGF-I, was synthesized by recombinant DNA technology. We found that this analog had binding characteristics similar to those of natural IGF-I in the radioreceptor assay system. We used this analog to characterize human erythrocyte IGF-I receptors as follows. Erythrocytes from 33 normal subjects specifically bound 6.9 +/- 0.7% (mean +/- SD)/2.8 X 10(9) cells/ml. Scatchard analysis of the binding data showed that the total number of receptors per erythrocyte was 13, and the affinity constant was 1.26 X 10(9) M-1, similar to that of other human IGF-I receptors previously reported. We also examined IGF-I receptors in patients with insulin receptor abnormalities. Although the specific values of IGF-I binding to erythrocytes were decreased or increased in parallel with those of insulin, the degrees of decrease or increase were much smaller. This suggests that the expression of insulin receptors and that of IGF-I receptors are discordant.

Serum high molecular weight form of insulin-like growth factor II from patients with non-islet cell tumor hypoglycemia is O-glycosylated.

Non-islet cell tumor hypoglycemia (NICTH) is one of major causes of fasting hypoglycemia. In some patients with NICTH, insulin-like growth factor II (IGF-II) produced by and secreted from the tumors is thought to be a hypoglycemic agent. In patients with NICTH, the major form of IGF-II is high molecular weight form of IGF-II, designated as big IGF-II. The generation of big IGF-II in the NICTH syndrome is unclear. It has been reported that in the patients with NICTH big IGF-II lacks normal E-domain O-linked glycosylation, suggesting that the patient's big IGF-II might be generated by abnormal processing of pro-IGF-II. However, we have found that the apparent size of big IGF-II varies in sera from the patients with NICTH, and that there is a possibility that slower migration pattern of IGF-II might be because of a different size of sugar moiety attached to pro-IGF-II. In the present study using the sera from 10 patients with NICTH, we investigated the effect of O-glycosidase digestion on migration of IGF-II and analyzed the results by Western immunoblot. By Western immunoblot analysis the big IGF-II was reduced in size to 9.5 kDa in the enzyme-treated sera of the 10 patients with NICTH. The migration pattern is similar to that observed in sera of normal subjects after O-glycosidase digestion. These data indicate that big IGF-II from patients with NICTH is O-glycosylated, and the sizes of the sugar moiety are larger than those from normal subjects suggesting abnormal glycosylation in NICTH.

Decreased serum levels of acid-labile subunit in patients with anorexia nervosa.

One of the observations in malnutrition is that serum insulin-like growth factor (IGF)-I levels are decreased, and this decrease is associated with an altered profile of IGF binding proteins (IGFBPs). In human circulation, IGFs are mostly present as an approximately 150-kDa ternary protein complex consisting of IGFs, IGFBP-3, and acid-labile subunit (ALS). In the present study, to clarify the effect of nutrition on serum ALS levels, we investigated 33 patients with anorexia nervosa. Serum levels of ALS were measured by RIA. Furthermore, we measured serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 levels in the patients. From these data, we investigated which was the best predictor of body mass index (BMI) as a nutritional status marker. In the patients with anorexia nervosa, the serum ALS levels ranged from 0.7-16.9, with a mean of 10.6 +/- 0.7 mg/L, and the levels were significantly lower than those of normal subjects (13.8 +/- 0.8 mg/L, P < 0.05). Serum ALS levels positively correlated with BMI (r = 0.41, P < 0.05), and the levels increased during treatment. The serum IGFBP-2 levels in the patients were increased (871 +/- 91 microg/L), and the levels inversely correlated with BMI (r = -0.52, P < 0.01). The serum IGF-I and IGFBP-3 levels were low (152 +/- 14 microg/L and 2.56 +/- 0.12 mg/L, respectively), and the levels positively correlated with BMI (r = 0.46, P < 0.01; and r = 0.39, P < 0.05, respectively). The serum IGFBP-2, IGF-I, and IGFBP-3 levels returned toward normal ranges as BMI in the patients improved during treatment. Serum IGF-II levels did not correlate with BMI (r = 0.24, P = 0.17). Stepwise regression analysis revealed that serum IGFBP-2 was the best marker of BMI among these variables. The present study suggested that ALS was regulated by nutritional status, the same as IGF-I, IGFBP-2 and IGFBP-3; but the serum IGFBP-2 was the best predictor of BMI as nutritional status marker among the parameters in patients with anorexia nervosa.

Plasma growth hormone response to growth hormone-releasing factor in acromegalic patients.

Synthetic growth hormone-releasing factor (hpGRF-44) (100 micrograms) was administered intravenously to ten acromegalic patients. The time when the peak of plasma GH occurred as well as the magnitude of the response were highly variable among these ten patients. From the GH response patterns the ten acromegalic patients were tentatively classified into three groups: (1) those highly GRF-dependent whose GH level increased to four times basal, (2) those moderately GRF-dependent whose GH level rose to less than two times basal and (3) those GRF-resistant whose GH level did not change. These data suggest that there may be differences in the GRF-receptor system in pituitary adenomas causing acromegaly.

Plasma growth hormone (GH) response to GH-releasing factor in normal children with short stature and patients with pituitary dwarfism.

Synthetic human pancreatic GRF (hpGRF-44) was administered as an iv bolus to 28 normal children with short stature and 27 patients with GH deficiency. After a dose of 1 or 2 micrograms hpGRF-44/kg BW, mean plasma GH levels peaked at 15 and 30 min, respectively, with corresponding values of 30.1 +/- 4.7 and 33.2 +/- 3.7 ( +/- SE) ng/ml in normal but short children. The overall plasma GH response was greater than that of other GH stimulation tests such as insulin-induced hypoglycemia, glucagon-propranolol or L-dopa administration. Plasma LH, FSH, TSH, PRL, and cortisol levels were not altered by hpGRF-44 injection. Sixteen of 27 patients with GH deficiency did not respond to a 2 micrograms/kg BW hpGRF-44. However, plasma GH increases to greater than 5 ng/ml occurred in the remaining 11 patients. Their GH levels reached peaks between 15 and 90 min, with values ranging between 5.8 and 17.8 ng/ml. Two of these responding patients were infused iv with hpGRF-44 at 2.5 micrograms/min for 90 min after receiving an iv bolus injection of 2 micrograms/kg BW. Their plasma GH levels increased and remained near peak values throughout the infusion period. However, no increase in plasma GH levels occurred after a second bolus injection of hpGRF-44 given at the end of the infusion. These results suggest that hpGRF-44 is useful for the diagnosis of GH deficiency in individuals with short stature and that some patients with GH deficiency, diagnosed on the basis of established tests, have GH responses to hpGRF-44.

Serum somatomedin A in chronic renal failure.

The serum levels of somatomedin A, determined by radioreceptor assay, were significantly higher in 57 adult patients with chronic renal failure (X = 2.57 +/- 0.12 U/ml) than in healthy subjects (n = 131; X = 0.77 +/- 0.02 U/ml). A positive correlation was found between somatomedin A and creatinine levels (r = 0.33), but somatomedin A levels did not decrease after hemodialysis. A reduction was only observed after successful renal allografting. Immunoreactive somatomedin A was also found to be increased in patients with chronic renal failure (X = 2.61 +/- 0.21 U/ml), whereas low levels were obtained by the chick bioassay. However, after separating the inhibitory factors from the stimulatory factors by gel chromatography at neutral pH, uremic serum was shown to contain increased levels of somatomedin activity. Although all somatomedin A, determined by different techniques, was present in high molecular forms, the elution pattern differed from that seen in patients with acromegaly.

Characterization of new monoclonal antibodies to human insulin-like growth factor-II and their application in western immunoblot analysis.

Four immunoglobulin G1 class monoclonal antibodies (mAbs; 1D5, 1D9, 2B11, and 2H11) were produced against recombinant human insulin-like growth factor-II (rhIGF-II). Enzyme-linked immunosorbent assay established that these four mAbs specifically recognized rhIGF-II and hIGF-II, but not rhIGF-I. mAbs 1D5, 1D9, and 2H11 did not cross-react with mouse rIGF-II, although there are only six amino acid differences between mouse IGF-II and human IGF-II. The epitope for each mAb was partially defined by enzyme-linked immunosorbent assay using mouse-human chimera IGF-II mutants and other IGF-II mutants that were prepared by site-directed mutagenic procedures. These results indicated that the epitopes of mAbs 1D5, 1D9, and 2H11 are in the C-domain of hIGF-II around Ala32 to Ser36, and that of 2B11 is in the carboxyl-terminal end of the B- and A-domains of hIGF-II. A specific and sensitive RIA was developed using mAb 2H11. In this RIA, IGF-II variant ([RLPG/S29]IGF-II) and rhIGF-II competed equally with [125I]IGF-II for binding to mAb 2H11. Similar results were produced when mAbs 1D5, 1D9, and 2B11 substituted for 2H11. The potential usefulness of mAb 2H11 in an immunoblot procedure to characterize the heterogeneity of IGF-II in the sera and tumor tissues of patients with nonislet cell tumor hypoglycemia was evaluated. A procedure that combined acid-ethanol extraction of serum or tumor tissues and immunoaffinity concentration of the extracted IGF-II with mAb 2H11-immobilized resin was found to be an effective way to prepare the samples. In Western immunoblots, a quantity of rhIGF-II as low as 3 ng could be identified, whereas 200 ng rhIGF-I or rat IGF-II were not recognized. The levels of IGF-II in the sera of 12 patients with nonislet cell tumor hypoglycemia varied from normal to about twice normal. The mol wt (M(r)) of this IGF-II was between 10-17K. There was little of the processed 7.5K M(r) IGF-II in the sera of these patients. Finally, the source of the high M(r) forms of IGF-II was the tumor, because the ratios of high M(r) forms of IGF-II to 7.5K IGF-II changed dramatically from 99:1 and 91:9 to 4:96 and 32:68 in two patients after successful excision of their tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on the response of growth hormone (GH) secretion to GH-releasing hormone, thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin in acromegaly.

The plasma GH response to GH-releasing hormone (GHRH), TRH, or GnRH administration was examined in 25 acromegalic patients. Plasma GH levels increased in 21 patients after GHRH, in 19 after TRH, and in 4 after GnRH. The four GHRH nonresponders had had acromegaly longer than had the GHRH responders. No specific combination of GH responsiveness to these 3 releasing hormones was found among the patients. Infusion of 1 mg GHRH for 150 min gradually increased plasma GH levels, with some fluctuations, from the beginning to the end of infusion in normal subjects and in 7 patients who were GHRH responders, but a bolus injection of 100 micrograms GHRH at the end of the infusion did not further elevate plasma GH levels. These results suggest that desensitization to GHRH occurred in the normal subjects and acromegalic patients. However, in 5 acromegalic patients who responded to both GHRH and TRH, a bolus injection of 500 micrograms TRH given at the end of the 150-min infusion of 1 mg GHRH evoked a further plasma GH rise. In 5 normal subjects and 2 patients who were responders to GHRH but not TRH, a bolus injection of 500 micrograms TRH did not cause plasma GH elevation at the end of 150-min infusion of 1 mg GHRH. These results imply that TRH and GnRH stimulate GH secretion from the adenoma cells in vivo through receptors different from those for GHRH. In vitro studies using cultured pituitary adenoma cells from 2 patients revealed that the responses of GH secretion to GHRH were similar to those in vivo. These data, therefore, suggest that the responsiveness of GH secretion to stimuli is determined by the specificity of the receptors on adenoma cells. The action of somatostatin-28 was more potent than that of somatostatin-14 in the suppression of GH secretion from adenoma cells.

Urinary growth hormone (GH) measurements are useful for evaluating endogenous GH secretion.

Daily (24-h) urinary GH excretion was measured using a highly sensitive sandwich enzyme immunoassay in 10 normal adults, 6 patients with hypopituitarism, 25 normal but short children who had normal plasma GH responses (peak plasma GH level, greater than 10 micrograms/L) to provocative tests, and 8 patients with acromegaly. The mean urinary GH values in the normal adults, patients with acromegaly, and patients with hypopituitarism were 13.8 +/- 4.0 (+/- SE) and 431.1 +/- 149.1 ng/g creatinine (Cr) (1.56 +/- 0.45 and 48.77 +/- 16.87 ng/mmol Cr) and undetectable, respectively; these mean values were significantly different from each other. In the normal but short children the urinary values ranged from undetectable to 55.8 ng/g Cr (6.31 ng/mmol Cr). All of the normal but short children and 4 patients with hypopituitarism participated in a 24-h endogenous GH secretion study. The urinary GH values correlated significantly with the mean 24-h plasma GH concentrations as an index of endogenous GH secretion (r = 0.81; P less than 0.001) and plasma somatomedin-C levels (r = 0.67; P less than 0.001), respectively. In 6 patients with acromegaly whose plasma GH levels were constant throughout a 4-h period, the urinary GH values also significantly correlated with the mean plasma GH levels (r = 0.95; P less than 0.01). These data indicate that urinary GH measurements reflect endogenous GH secretion and that measurement of urinary GH excretion is a useful, simple, and practical method for evaluating endogenous GH secretion.