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PubMed1996

Growth hormone-binding protein in the goat: characterization, evolution under exogenous growth hormone treatment, and correlation with liver growth hormone receptor levels.

This report describes the identification and characterization of a specific, high-affinity growth hormone-binding protein (GHBP) in lactating goat serum. Serum samples were incubated with [125I]human GH as ligand and in the absence or in the presence of bovine GH as competitor. GH-GHBP complex formation was performed by high-performance liquid chromatography, and the radioactivity was recorded on-line with a Berthold LB detector connected to a computer. The results showed that a serum protein was able to bind specifically to human GH and bovine GH but not to ovine prolactin. Scatchard plots indicated an affinity constant of 4.5 x 10(8) M-1 and a maximum binding capacity of 4.8 x 10(-10) mol/l. In addition, we conducted a 4-wk study to determine the effects of recombinant bovine GH administration on milk production in lactating goats. The effects of recombinant bovine GH treatment on milk production and on the regulation of GHBP and hepatic GH receptor levels were studied. As expected, recombinant bovine GH injected daily increased yields of milk, fat, protein (40, 61, and 40%, respectively), and circulating insulin-like growth factor 1 concentrations compared with controls. During the pretreatment and treatment periods, the control goats exhibited a constant amount of GHBP in serum. No consistent effect of GH treatment on GHBP level was observed. The binding of [125I]bovine GH to hepatic microsomal membranes of GH-treated goats was significantly decreased compared with that of control goats. After MgCl2 desaturation of membranes, the results demonstrated that the down-regulation of GH hepatic receptors, observed for the treated goat group, was induced by receptor occupancy without modification of binding affinity. The GH receptor gene expression, analyzed by slot blot and hybridization with an [alpha-32P]GH receptor cDNA probe, was not modified by the GH treatment. In lactating goats, the galactopoietic effect of exogenous GH involved a hepatic receptor occupancy. The individual concentration of GHBP in serum cannot explain the individual variations of responses to GH treatment in goats.

Animals↗
PubMed1985

Differential effects of parathyroid hormone responsive cultured human cells on biological activity of parathyroid hormone and parathyroid hormone inhibitory analogues.

We have employed parathyroid hormone (PTH) responsive human cells cultured from dermis or giant cell tumors of bone (GT) to evaluate the biological properties of a newly developed in vivo PTH inhibitor, [Tyr34]bPTH-(7-34)-amide (PTH-Inh). Short periods of incubation of cells from dermis or GT with maximal stimulatory concentrations of PTH in the presence of increasing concentrations of PTH-Inh resulted in a dose-dependent inhibition of the adenosine cyclic 3',5'-phosphate (cAMP) response (Ki = 3 X 10(-7) M and 4.2 X 10(-7) M for GT and dermal cells, respectively). In both cell cultures, PTH-Inh alone did not increase cAMP levels, and in desensitization experiments, preincubation with PTH-Inh alone did not desensitize cells to PTH. Hence, the analogue displayed no agonist properties. Unexpectedly, when PTH-Inh was incubated with dermal cells in the presence of PTH, the PTH-Inh failed to block desensitization, suggesting a loss of biological effectiveness of the inhibitor. When medium containing PTH-Inh alone was removed from dermal cells and tested for inhibition of the acute PTH response in untreated cells, there was apparent loss of inhibitory efficacy (t1/2 = 20 h). In contrast, incubation of native PTH or bPTH-(1-34) with cells did not affect the biological activity of these ligands. Unlike the dermal cells, the PTH-Inh did block desensitization to PTH in GT, and there was no loss of inhibitor efficacy when medium containing PTH-Inh was incubated with GT (48 h) and then tested in untreated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Assay↗
PubMed1998

Outpatient assessment of residual growth hormone secretion in treated acromegaly with overnight urinary growth hormone excretion, random serum growth hormone and insulin like growth factor-1.

OBJECTIVE: To assess the outpatient investigations, overnight urinary growth hormone (uGH) excretion, random serum GH and insulin like growth factor 1 (IGF-1), and GH indices from the oral glucose tolerance test (OGTT) (fasting, nadir and mean GH), as measures of mean GH secretion in treated acromegaly, in comparison with a GH day series, which served as a gold standard. DESIGN: Prospective cross-sectional study, with patients admitted to a metabolic ward for the following investigations: random GH, IGF-1, 6 point GH day series (day 1), 9 h timed overnight uGH excretion, OGTT with GH response (day 2). Agreements between the mean GH during the day series and the other outcome measures, and the diagnostic performance of the latter, for the presence or absence of active acromegaly (mean GH during day series > or = 5 or < 5 mU/l, respectively) were determined. PATIENTS: 26 patients with treated acromegaly (11 with inactive acromegaly off drug therapy). MEASUREMENTS: Serum GH and uGH were measured by immunoradiometric assays and IGF-1 by radioimmunoassay. RESULTS: Agreements with the mean GH during the day series were perfect for the nadir GH during the OGTT with a 2 mU/l cutoff (Cohen's kappa (kappa) = 1, P < 0.00001), almost perfect for the fasting and mean GH throughout the OGTT (both kappa = 0.92, P < 0.0001) and random GH (kappa = 0.85, P < 0.0001), and substantial for the nadir GH with a 5 mU/l cutoff (kappa = 0.77, P < 0.0001), IGF-1 (kappa = 0.62, P < 0.001) and overnight uGH excretion (kappa = 0.61, P = 0.002). Nadir GH with a 2 mU/l cutoff was completely accurate for diagnosing the presence or absence of active acromegaly (positive and negative predictive values (% +/- standard error percentage) 100 +/- 8% and 100 +/- 10%). None of the outpatient tests used alone was an adequate diagnostic test (positive and negative predictive values: overnight uGH excretion -86 +/- 10% and 75 +/- 13%; random GH -100 +/- 11% and 85 +/- 11%; IGF-1 -92 +/- 10% and 71 +/- 13%) and so combinations of tests were assessed. The best was overnight uGH excretion plus random GH (positive and negative predictive values 88 +/- 9% and 100 +/- 12%). Using all three outpatient investigations, the positive predictive value of three raised results was 100 +/- 13%. CONCLUSIONS: In treated acromegaly, residual GH secretion can be reliably assessed with the OGTT, using standard diagnostic criteria. It can also be assessed on an outpatient basis with overnight uGH excretion and random GH, as direct measures, and IGF-1. If these are all normal, active acromegaly is excluded. Three raised results denote active acromegaly, and one or two raised results would need further investigation with a GH day series.

Acromegaly↗
PubMed1999

Negative regulation of gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor gene expression by a gonadotrophin-releasing hormone agonist in the rat hypothalamus.

There exists evidence for the presence of ultrashort loop feedback circuits of gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus. It is, however, uncertain whether a similar mechanism is involved in the regulation of GnRH gene expression in vivo. Furthermore, little is known about the regulation of GnRH receptor (GnRHR) expression in the brain. In the present study, we examined the regulation of GnRH and its receptor gene expression by GnRH in vivo. A GnRH agonist, [D-Ala6, des-Gly10]GnRH-ethylamide (des-Gly GnRH), was administered by intracerebroventricular (i.c.v.) injection via the lateral ventricle of ovariectomized and estradiol (OVX + E)-treated rats. The amounts of GnRH and GnRHR mRNA were measured in the preoptic area (POA) and posterior mediobasal hypothalamus (pMBH) micropunch samples from individual rat brain slices by respective competitive reverse transcription-polymerase chain reactions. The i.c.v. administration of des-Gly GnRH significantly decreased GnRH and GnRHR mRNA expression in a dose-and time-related manner: des-Gly GnRH (6 ng) suppressed GnRH and GnRHR mRNA expression within 2 h, and the suppression was maintained without significant variation until 8 h after treatment. Treatment with Antide, [N-Ac-D-Nal(2)1, pCl-D-Phe2, D-Pal(3)3, Lys(Nic)5, D-Lys(Nic)6, Lys(iPR)8, D-Ala10]GnRH (10 ng), a potent GnRH antagonist, did not alter GnRH mRNA expression, but prevented des-Gly GnRH-induced suppression of GnRH mRNA expression. Antide alone decreased GnRHR mRNA expression, but failed to alter agonist-induced suppression of GnRHR mRNA expression. These results demonstrate the existence of an ultrashort loop feedback mechanism for GnRH gene expression in the POA, along with homologous down-regulation of GnRHR mRNA expression in the pMBH.

Animals↗
PubMed1983

The effect of growth hormone treatment alone or growth hormone with supplemental zinc on growth rate, serum, and urine zinc and copper concentrations and hair zinc concentration in patients with growth hormone deficiency.

Previous studies suggest that growth hormone (GH) may increase daily zinc requirements to meet the demand of growing bone and to replace increased urinary losses. We tested the hypothesis that zinc or copper availability might be limiting factors in the response of children receiving GH replacement. Ten patients with GH deficiency were followed for GH-induced changes in urine and serum zinc and copper during acute (0.3 IU/kg/day X 5 days) and chronic GH treatment (0.1 IU/kg/tiw). Zinc was measured in hair collected every 3 months. Zinc sulfate (220 mg/day) was given to half the patients during the second year of treatment. There was no evidence of zinc or copper deficiency, and zinc supplements did not venhance growth response to GH during the second year of treatment. We conclude that GH treatment in children does not alter serum or urine zinc or copper or hair zinc, and zinc supplementation does not improve growth in children with GH deficiency.

Adolescent↗
PubMed1993

Effect of growth hormone administration frequency on 24-hour growth hormone profiles and levels of other growth related parameters in girls with Turner's syndrome. Dutch Working Group on Growth Hormone.

OBJECTIVE: The optimal dose and frequency of GH administration in Turner's syndrome is unknown. There is some evidence that a schedule which mimics normal pulsatile GH secretion may be more effective than a single daily dose. We therefore wished to study the influence of the frequency of GH administration on 24-hour GH profiles and levels of other growth-related factors in Turner's syndrome. DESIGN: Four weeks after initiation of 0.05 microgram/kg/day ethinyl oestradiol, we compared twice daily (b.i.d.-fractionated dose) with once daily (o.d.) s.c. injections of 6 IU GH/m2/day in a 2-week cross-over design with a 2-week washout interval. Each treatment period was concluded with 24-hour GH profile tests. Pretreatment plasma/serum levels of GH, IGF-I, binding proteins for GH (GHBP) and IGF-I (IGFBP-3) were used as a basis for comparison of the levels found after each regimen. A one-compartment open model was used for estimation of pharmacokinetic parameters. SUBJECTS: Ten previously untreated girls with Turner's syndrome aged > or = 11 years. MEASUREMENTS: Plasma levels of GHBP by standardized binding assay; GH, IGF-I, and IGFBP-3 serum/plasma levels by radioimmunoassay. RESULTS: There were significantly higher maximum GH levels and a greater area under the curve with o.d. than with b.i.d. GH, while GH clearance was greater with b.i.d. The pharmacokinetic values with o.d. injections were in conformity with values for healthy and GH-deficient children. Pretreatment GHBP levels tended to be high compared with values in healthy prepubertal children. These levels decreased with GH therapy, significantly so with b.i.d. GH only. There was a significant increase in levels of IGF-I and IGFBP-3, irrespective of regimen. The IGF-I to IGFBP-3 ratio, a possible indicator of the growth response, rose significantly and comparably with both regimens. There was no consistent diurnal variation with either regimen in GHBP, IGF-I or IGFBP-3 levels. Four-hourly levels of GH, GHBP, IGF-I and IGFBP-3 were not correlated. CONCLUSIONS: Although the 24-hour profiles differed during once or twice daily administration of the same total growth hormone dose, the diurnal pattern and mean levels of factors involved in the biological effects of GH are comparable for both regimens.

Adolescent↗
PubMed1995

Long-term results of growth hormone therapy in children with short stature, subnormal growth rate and normal growth hormone response to secretagogues. Dutch Growth Hormone Working Group.

BACKGROUND AND OBJECTIVE: Growth hormone treatment in children with idiopathic short stature (ISS) leads to growth acceleration in the first years, but the effect on final height is still poorly documented. We therefore studied the long-term effect of GH therapy in children with idiopathic short stature. DESIGN: We have treated 27 prepubertal children with ISS with recombinant human GH (rhGH) in an initial dosage of 2 IU/m2 body surface/day subcutaneously, which was doubled either after the first year if the height velocity increment was less than 2 cm/year, or thereafter if height velocity fell below the P50 for bone age. Growth and bone maturation of the treatment group (ISS group, n = 21) were compared to those of an untreated control group with ISS (ISS controls, n = 27) and of a group of rhGH treated children with isolated GH deficiency (GHD group, n = 7). RESULTS: In 9 patients of the ISS group still on treatment, height standard deviation score (HSDS) for chronological age increased from -3.8 +/- 0.7 to -2.3 +/- 0.9 (mean +/- standard deviation) over 6 years, while in matched ISS controls HSDS for age did not change. HSDS for age in the GHD group increased from -3.9 +/- 0.6 to -1.8 +/- 0.7 after 4 years, significantly more than the ISS group. Bone maturation was accelerated in the ISS and GHD groups. HSDS for bone age and predicted adult height did not change in either group. Final height in 12 children of the ISS group was -2.6 +/- 1.0 SDS. In the untreated controls final height was similar. A low integrated GH concentration over 24 hours, a low GH peak to provocative stimuli, and minimal initial BA delay predicted a favourable outcome. CONCLUSION: rhGH treatment in this group of children with idiopathic short stature did not increase average final height. Part of the heterogeneity of the response can be attributed to the variation in endogenous GH secretion and initial bone age delay.

Body Height↗
PubMed1987

Recombinant-DNA-derived bovine growth hormone from Escherichia coli. 1. Demonstration that the hormone is expressed in reduced form, and isolation of the hormone in oxidized, native form.

The isolation of bacterially synthesized, recombinant-DNA-derived, bovine growth hormone (r-bGH) with native structure is described. The r-bGH is found in insoluble form, in a pellet fraction, after cell breakage and centrifugation. Cell envelope components (protein, lipid, endotoxin) and nucleic acids are selectively removed from the pellet fraction by an EDTA/lysozyme/deoxycholate extraction. We demonstrate that the r-bGH is largely reduced until solubilized using 6 M guanidine/HCl. Air oxidation is then carried out, in the presence of the guanidine/HCl. The oxidation results in a mixture of about one-third disulfide-linked oligomers and two-thirds oxidized monomer. The latter may include some incorrectly oxidized material, but appears to be mostly correctly oxidized. The oxidized monomer is isolated by gel filtration in the presence of guanidine/HCl. Subsequent guanidine/HCl removal leads to refolded, oxidized r-bGH. All steps in the procedure, in particular the oxidation and refolding steps, can be carried out at relatively high protein concentrations.

Animals↗
PubMed1998

Growth hormone replacement in an adult with mild growth hormone deficiency and hereditary motor and sensory neuropathy: growth hormone restores independent mobility.

We present the case of an adult patient with growth hormone (GH) insufficiency and hereditary motor and sensory neuropathy type 1. Stopping GH replacement at the attainment of final height was associated with a marked reduction in power and mobility, resulting in the patient becoming wheelchair bound. GH replacement was assessed in a double-blind placebo-controlled trial. During the GH replacement arm of the trial, the patient's mobility and independence returned to previous levels. We suggest that the indications for GH replacement in adults should take account of other medical problems, in particular neuromuscular disorders, as well as the degree of GH deficiency.

Adolescent↗
PubMed1993

Effect of timing of growth hormone administration on plasma growth-hormone-binding activity, insulin-like growth factor-I and growth in children with a subnormal spontaneous secretion of growth hormone.

Since normal pulsatile growth-hormone (GH) secretion displays a major and consistent surge during sleep, we studied the effect of timing of GH supplementation on plasma GH-binding protein activity (GH-BP), insulin-like growth factor-I (IGF-I) and growth. 34 prepubertal subjects (28 boys, 6 girls) aged 8-11 years, of short stature (< 2 SD for age), with a GH response to provocative test > 10 micrograms/l and a subnormal 24-hour GH secretion (< 3 micrograms/l), were randomly allocated to receive Bio-Tropin (recombinant GH, Bio-Technology, Israel) 0.81 IU/kg/week in 3 equally divided doses. GH was administered either at 8.00-10.00 h (M group), 14.00-16.00 h (AN group) or 19.00-21.00 h (NT group). Height velocity, IGF-I and GH-BP were determined prior to and after 6 and 12 months on GH therapy in the three groups. There was no significant difference between the three groups in the growth response, IGF-I and GH-BP increase, all of which increased significantly during GH therapy. Although GH levels after the injection decline to preinjection levels after 10 h, the changes induced by GH therapy, as reflected in IGF-I and GH-BP, last in the circulation long enough to prevent fluctuations in its action. The similarity of IGF-I and of GH-BP levels in the three treatment groups might explain the similar growth effects of the 3 protocols.

Carrier Proteins↗
PubMed1995

Final height in a large cohort of Dutch patients with growth hormone deficiency treated with growth hormone. Dutch Growth Hormone Working Group.

Final height was evaluated in 203 patients with growth hormone (GH) deficiency, who had been treated with GH in childhood, and was related to other factors. Mean final height was 168.1 cm (men) and 154.7 cm (women), -2.07 and -2.20 SD of the population mean, respectively. Patients with GH deficiency due to cerebral tumour were taller than those with idiopathic GH deficiency, and patients with induced puberty were taller than those with spontaneous puberty. Target height (r = +0.37), birth length (r = 0.36), height SDS at the start of therapy (r = +0.51) and at the start of puberty (r = +0.58) were significantly correlated with final height. Multiple linear regression analysis revealed that after correction for height at the start of puberty, age at the start of puberty was also positively correlated with final height. Patients who were treated after 1983 (when treatment regimens were changed) were taller than patients who finished treatment before 1983. The results suggest the importance of preventing a large initial height deficit and attaining optimal height at the start of puberty.

Adolescent↗
PubMed1995

Nocturnal urinary growth hormone excretion in growth hormone-deficient children on and off growth hormone treatment.

Non-compliance has been reported as a major issue in growth hormone (GH) therapy. We explored the use of urinary GH (uGH) measurements to monitor the GH treatment of 18 children (aged 5-16 years) diagnosed as GH deficient on the basis of history, phenotype, auxology and peak GH concentration during 2 provocation tests of < 15 mU/l. Each child collected 5 consecutive overnight urine samples while on GH replacement schedules, then discontinued treatment for 2 days and collected a further 5 urine samples. The mean mass of uGH excreted on treatment (8.6 ng, range 3.6-13.0 ng) was significantly greater than that off treatment (1.2 ng, range 0.6-2.7 np; p < 0.01). All uGH values on treatment exceeded the mean nocturnal uGH excretion of normal age- and sex-matched children. The clear distinction between uGH levels on and off GH treatment indicates that uGH measurement would determine whether two or more GH injections had been missed. A series of uGH estimates over a 2-week period may provide a realistic perspective on injection frequency.

Adolescent↗
PubMed1971

The effect of administration of human growth hormone on the plasma growth hormone, cortisol, glucose, and free fatty acid response to insulin: evidence for growth hormone autoregulation in man.

The effect of administration of human growth hormone (HGH) (3 mg every 6 hr for 6 days) on the endogenous GH response to insulin-induced hypoglycemia at 8, 12, 24, and 48 hr posttreatment was studied in 11 healthy male adults. Free fatty acid, cortisol, and glucose responses pre- and posttreatment with HGH were evaluated concurrently. Control subjects received saline injections to evaluate relationship of GH responses to the periodicity of insulin tolerance tests. The data were compared for each subject pre- and posttreatment with HGH as well as by comparison of the results of the saline-treated group with those of the HGH-treated group. The mean maximal GH concentration in response to insulin-induced hypoglycemia for all the subjects (n = 16) was 31.1 +/-3.6 ng/ml (+/-SEM) on day 1 of the control period and 23.4 +/-3.1 (SEM) on day 2, not statistically significant.A significant decrease in the maximal peak GH response (n = 8) after insulin-induced hypoglycemia was observed at 8 and 12 hr after HGH administration was terminated with mean peak values for GH of 4.6 +/-1.3 ng/ml and 10.4 +/-1.9 ng/ml, respectively (P < 0.01). A progressive return to control values was noted between 12 and 24 hr. The GH responsiveness of the saline-treated group (n = 5) was unchanged from that observed during the control period. The fasting glucose values were unchanged in the GH-treated group from those of the control period or of the saline-treated controls. Insulin resistance was apparent at 8 hr posttreatment with HGH. No differences in FFA response after insulin-induced hypoglycemia were observed in GH-treated or saline-treated subjects. The rise in plasma cortisol after insulin-induced hypoglycemia was comparable in the GH-treated and saline-treated group. Diurnal variation in plasma cortisol was maintained during the period of GH suppression. These observations support the concept that GH can modulate its secretion by means of an auto-feedback mechanism.

Adult↗
PubMed1990

Hormonal responses to a potent gonadotropin hormone-releasing hormone antagonist in normal elderly men.

GnRH analogs, both agonists and antagonists, have potential use in androgen-dependent diseases of older men, such as prostatic cancer and benign prostatic hyperplasia. Previous experience with agonists of GnRH has suggested that GnRH analogs may be more effective in aged men than in young men, but little is known about GnRH antagonists in older men. Therefore, we evaluated the hormonal effects of a single dose and a short course of a GnRH antagonist (Nal-Glu) in normal elderly men. Six young men (25-34 yr old) and six older men (66-76 yr) each received single morning injections of Nal-Glu (25, 75, and 250 micrograms/kg), separated by 2 weeks. Serum levels of testosterone (T), immunoreactive LH (LH RIA) and FSH (FSH RIA), and bioactive LH (LH BIO) were evaluated periodically for 7 days after each injection. In addition, six elderly men received 25 and 75 micrograms/kg.day Nal-Glu for 10 consecutive mornings each, and serum levels of T, inhibin, LH RIA, LH BIO, FSH RIA, and bioactive FSH were evaluated. Nal-Glu in all three single doses caused a significant (P less than 0.01) decline in serum levels of T and gonadotropins that was similar in extent in the elderly and young men. For example, T declined to a level of 19% of baseline after the 250 micrograms/kg dose of Nal-Glu in both age groups. For both the young and elderly men, the major effect of increasing the Nal-Glu dose was a prolongation of the period of suppression. Multiple Nal-Glu injections in the elderly men also resulted in a rapid decline in T, inhibin, and bioactive and immunoreactive gonadotropins. For both LH and FSH, bioactivity decreased to a greater extent than immunoreactivity. Local side-effects of Nal-Glu tended to be fewer and of less intensity in the elderly men compared to those in the young men. These results demonstrate that the response to Nal-Glu in healthy elderly men is similar to that in younger men, and extended administration of Nal-Glu in elderly men effectively suppresses gonadal and pituitary function. These results suggest that the role of GnRH antagonists in the effective treatment of androgen-dependent disease in the aging male needs to be explored further.

Adult↗
PubMed1996

An open 36-month study of lipid changes with growth hormone in adults: lipid changes following replacement of growth hormone in adult acquired growth hormone deficiency.

Interest in adult growth hormone replacement has increased since identification of the associated vascular morbidity and mortality. Although total cholesterol and low density lipoprotein reduction and high density lipoprotein increases are anticipated, reports are conflicting and there is no uniformity in lipoprotein(a) changes. In 1990 we commenced an open trial of therapy with human recombinant GH and now have results to 36 months for 21 patients. Deficiency status was confirmed by insulin stress test with flat GH response < 2.0 ng/ml, mean insulin-like growth factor-I value 122 ng/ml (+/- 69 SD). Lipoprotein(a) was measured by monoclonal assay. Lipid analysis yields two subgroups: baseline cholesterol levels of greater or less than 6.22 mmol/l, with hypercholesterolaemic patients showing an enhanced hypolipaemic response. ANOVA was utilized, with 95% confidence limits. The most significant changes are of reductions in cholesterol and low density lipoprotein; the rate of change is greatest at 6 and 12 months but not sustained to 36 months. High density lipoprotein rises as expected, not to full significance. Lipoprotein(a) levels rose significantly in six patients of the cohort, and the increase was sustained over 36 months.

Adult↗
PubMed1977

Immunological studies on parathyroid hormone: characterization of antisera against synthetic 1-34 human parathyroid hormone and evidence that position 30 in human parathyroid hormone is aspartic acid.

Radioimmunoassays for the measurement of the 1--34 human parathyroid hormone fragment (1--34 hPTH) were developed using antisera raised in rabbits against synthetic 1--34 hPTH-N (amino acid sequence proposed by Niall). Binding of 125I-labelled 1--34 hPTH-N to these antisera was optimal at pH 5-5. Limits of detection varied between 25 and 200 pg/ml. Cross-reactivity of 1--34 bovine PTH was substantial in all assays; 1--34 hPTH-B (structure proposed by Brewer), 1--84 hPTH and 1--29 hPTH cross-reacted only with antisera from one animal. 1--29 Human PTH was obtained from partial hydrolysis of both 1--84 hPTH and 1--34 hPTH-N. Production of 1--29 hPTH from 1--84 hPTH was demonstrated by comparison of the elution profiles of the reaction product and 1--29 bovine PTH on Sephadex G-50. Thus, evidence was obtained that position 30 in native hPTH is occupied by an aspartic acid residue.

Animals↗
PubMed1998

Co-localization of human growth hormone and human prolactin in hormonally pure human growth hormone-producing pituitary adenomas.

Co-localization of human growth hormone (hGH) and human prolactin (hPRL) in hGH-producing pituitary adenomas was examined by electron microscopy with immunoblot analysis. At the electron microscopic level using anti-hGH or anti-hPRL polyclonal antibody, hGH and hPRL were found to be co-localized within each of the secretory granules in one of five cases. Double-labeling electron immunocytochemistry using colloidal gold particles of different sizes was effective in demonstrating this co-localization. As an additional step, we performed immunoblot analysis of hGH-producing pituitary adenomas using monoclonal antibodies. Four hGH-producing adenomatous tissue samples contained several hPRL-immunoreactive bands. In Case 2, the main 23K hPRL band was stained especially strongly The immunoblotting analysis of purified hGH using both anti-hPRL polyclonal antibody and monoclonal antibody to asses cross-reaction of the polyclonal anti-hPRL antisera with hGH revealed that both monoclonal and polyclonal antibodies were suitable for determining the co-localization. Double-labeling techniques using anti-hGH and anti-hPRL monoclonal antibodies demonstrated that only a few secretory granules were positive for co-localization of both hGH and hPRL (Case 2). The present study, which used not only polyclonal but also monoclonal antibodies, suggests that some hGH-producing pituitary adenomas contained both hPRL and hGH in the same secretory granules of tumor cells.

Adenoma↗