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Biomedical subjects

N Ling

Publications and source records attributed to N Ling.

At least 289 records · Page 16Linked to original sources
PubMed1984

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.

Acromegaly↗
PubMed1984

Gonadotropin-releasing activity of alpha-melanocyte-stimulating hormone in normal subjects and in subjects with hypothalamic-pituitary dysfunction.

The gonadotropin-releasing activity of synthetic alpha MSH, previously found in normal men, was evaluated in women with different hormonal environments and in patients with acyclic gonadotropin release due to hypothalamic-pituitary dysfunction. alpha MSH (2.5 mg, iv) administered as either a single or two repeated pulses (at 2-h intervals) elicited unequivocal pituitary release of LH in normal women during the luteal phase and midcycle surge and in patients with functional hypothalamic amenorrhea, hyperprolactinemic amenorrhea, and polycystic ovary syndrome. Concomitant release of LH and FSH occurred only in polycystic ovarian syndrome patients and normal men. alpha MSH had no discernible effect on gonadotropin release in women during the early and late follicular phases of the cycle, in postmenopausal women, and in patients with isolated gonadotropin deficiency, even after pulsatile GnRH priming. The present observations confirm and extend our earlier finding that alpha MSH possesses gonadotropin-releasing activity in men and indicate that alpha MSH has similar properties in women with progesterone- and androgen-dominated environments or with specific types of hypothalamic-pituitary dysfunction marked by attenuated GnRH-LH release.

Adult↗
PubMed1984

Immunoreactive growth hormone-releasing factor in human stalk median eminence.

Immunoreactive growth hormone-releasing factor was detected in extracts of acetone preserved human stalk median eminence utilizing an antiserum against human GRF-(1-44)-NH2, isolated from a pancreatic tumor. The antibody is highly specific for the C-terminus of GRF-(1-44)-NH2, and has a cross-reactivity less than 0.02% with GRF-(1-40) free acid, a peptide isolated from a different pancreatic tumor. The mean concentration of IR-GRF in 5 pools of 10-15 stalk-median eminence fragments was 57.7 +/- 7.2 ng/mg protein (mean +/- SEM, range 42.5-75.8 ng/mg protein). Gel filtration chromatographic analysis showed that 97% of the IR-GRF coeluted with synthetic hpGRF-(1-44)-NH2 and eluate inhibition of binding in the radioimmunoassay was parallel to that of hpGRF-(1-44)-NH2. These data strongly suggest that human hypothalamic tissue contains a peptide that is similar to hpGRF-(1-44)-NH2.

Chromatography, Gel↗
PubMed1984

Distribution of growth hormone-releasing hormone-like immunoreactivity in human tissue extracts.

A specific RIA for human pancreatic tumor GH-releasing hormone [hpGRH(1-44)NH2] was developed using an antiserum which recognizes the region (Met27-Leu44)NH2 of hpGRH(1-44)NH2. This RIA was used to measure GH-releasing hormone-like immunoreactivity (GRH-LI) in various human tissue extracts. The highest concentration of GRH-LI was detected in extract of pituitary stalk with moderate amounts found in hypothalamus and optic chiasm but none in the cerebrum, cerebellum, medulla oblongata, spinal cord, and anterior pituitary. In peripheral organs appreciable quantities of GRH-LI were found in the pancreas, whereas extracts of thyroid, lung, stomach, duodenum, ileum, colon, adrenal, and kidney contained very low concentrations of GRH-LI. No GRH-LI was detected in liver and spleen extracts. Gel permeation chromatographic analysis of the tissue extract from the hypothalamus revealed only one peak which eluted at the same position as that of 125I-hpGRH(1-44)NH2. Similar analysis of an extract from the optic chiasm showed one peak at the same position as that of 125I-hpGRH(1-44)NH2 and another peak which eluted after hpGRH(1-44)NH2. In contrast, an extract from the pancreas contained only one peak which eluted before 125I-hpGRH(1-44)NH2, indicating a possible precursor form of hpGRH(1-44)NH2. Limited trypsin digestion of the GRH-LI material from the pancreas, followed by gel permeation chromatographic analysis, yielded a major peak eluting at the same position as that of 125I-hpGRH(1-44)NH2. These results suggest that the GRH-LI detected in the hypothalamus most likely corresponds to hpGRH(1-44)NH2 in structure and that the GRH biosynthesized in the hypothalamus is transported to the stalk median eminence and stored there for release into the portal vessels.

Adult↗
PubMed1984

Plasma growth hormone secretion during constant growth hormone-releasing factor infusion.

Synthetic human pancreatic growth hormone-releasing factor (hpGRF-44) was infused intravenously at a constant rate of 2.5 micrograms/min for 180 minutes in 3 normal boys of short stature. Plasma GH levels reached a peak at 60-120 min with a mean value (+/- SEM) of 69.1 +/- 14.3 ng/ml, and then, declined gradually in spite of continuous hpGRF-44 infusion up to 180 minutes. Similarly, constant infusion of hpGRF-44 at a rate of 2.5 micrograms/min in 5 normal but short boys for 90 minutes, together with an iv bolus injection of hpGRF-44 (2 micrograms/kg) administered at 0 and 90 minutes, elicited a prompt rise in plasma GH 15-30 minutes after the first bolus but no significant elevation of GH was observed after the second bolus. In contrast, when two iv bolus injections of hpGRF-44 (2 micrograms/kg) were given in 4 normal boys with short stature at 0 and 90 minutes, respectively, significant elevation of plasma GH was found after each bolus. These results suggest that under constant infusion of GRF the pituitary experiences a down-regulation after the initial peak of GH response, possibly due to desensitization to GRF.

Adolescent↗
PubMed1984

Arginine hydrochloride stimulation of serum potassium and aldosterone is enhanced by somatostatin-28.

Potassium, aldosterone and insulin responses to arginine infusion were compared in 5 normal men during infusions of somatostatin-14 (SS-14), somatostatin-28 (SS-28) and a control infusion. SS-14 and SS-28 were infused continuously at a rate of 8.6 pmol/min/kg and arginine (0.5 g/kg) was infused from 30-60 min. Following the control infusion with arginine hydrochloride, serum aldosterone and potassium levels increased slightly. The rise in potassium appears to be due to an exchange of cellular potassium for the proton from the arginine hydrochloride. SS-14 had no significant effect on serum potassium or aldosterone but an equimolar dose of SS-28 significantly enhanced the rise in potassium and aldosterone. SS-28 completely inhibited the arginine-stimulated insulin increase while SS-14 only partially inhibited the insulin increase. Since insulin opposes the increase in serum potassium by stimulating cellular uptake of this cation, the enhanced rise in serum potassium in response to arginine hydrochloride during the SS-28 infusion is likely due to the potent insulin suppressing effect of SS-28. The rise in serum aldosterone is directly related to the degree of elevation of serum potassium. These findings caution against the infusion of SS-28 during an arginine stimulation test.

Acid-Base Equilibrium↗
PubMed1984

In vitro and in vivo evidence that the C-terminus of preproenkephalin-A circulates as an 8500-dalton molecule.

One of the major immunoreactive components of the enkephalin precursor BAM-22P in extracts of adrenal medulla is a molecule of approximately 8500 Da. A similar component is detected, after gel-permeation chromatography, in extracts of bovine plasma and in culture medium harvested from acetylcholine-stimulated bovine adrenomedullary cells in culture. Simultaneous detection of the C-terminal epitome of preproenkephalin-A: Met-enkephalin-Arg6-Phe7-OH in this secreted high-molecular-weight zone suggest that the approximately 8500-Da form of BAM-22P is the C-terminal of preproenkephalin A.

Adrenal Medulla↗
PubMed1984

[Roles of cyclic AMP and calcium in the mechanism of the release of growth hormone by somatocrinin].

Growth hormone (GH) release from Rat pituitary cell monolayers in response to synthetic somatocrinin (7.8 to 1,000 pmol/l) is paralleled with an increase in cellular cyclic AMP (cAMP) content and efflux of cAMP in the extracellular medium. Somatostatin and blockers of calcium-dependent cellular mechanisms inhibit somatocrinin-induced GH release but only partially decrease (somatostatin, CoCl2) or even increase (trifluoperazine) cAMP levels. Thus, calcium is required for somatocrinin action and GH release is not simply dependent on stimulation of cAMP metabolism.

Animals↗
PubMed1984

Synergistical effects of ovine corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) on the release of pro-opiomelanocortin (POMC) related peptides by pituitary adenoma of a patient with Nelson's syndrome in vitro.

The effects of synthetic ovine corticotropin-releasing factor (oCRF), arginine vasopressin (AVP), alpha-melanocortin (alpha MSH), and dexamethasone on the release of pro-opiomelanocortin (POMC)-related peptides were studied on a pituitary adenoma of a patient with Nelson's syndrome. CRF, at doses up to 100 ng/ml, has no effect on IR-ACTH, IR-hNT or IR-beta LPH secretion by the pituitary adenoma cells within the first week of monolayer culture. During the second week of in vitro conditions, however, the cells responded to oCRF (1-100 ng/ml) with a significant increase in all three POMC-related peptides. AVP (10 and 100 ng/ml) was effective in stimulating secretion of the three POMC-related peptides on day 6 in vitro; in addition, during the second week in culture, AVP (1 ng/ml) acted synergistically with 1-100 ng/ml of oCRF to release IR-ACTH, IR-hNT and IR-beta LPH at least 3-4 fold higher than CRF alone. alpha MSH (10 micrograms/ml) and dexamethasone (10(-6)M) did not alter the release of any of the three peptides. These results demonstrate that CRF and AVP can act synergistically on human pituitary tissue in vitro to promote the release of POMC-related peptides and also in vivo as shown by others.

Adenoma↗
PubMed1983

Isolation and characterization of the bovine hypothalamic growth hormone releasing factor.

A 44 amino acid peptide with high intrinsic growth hormone releasing activity was isolated from 500 bovine hypothalami by means of acid extraction, immunoaffinity chromatography, gel filtration, and two steps of reverse phase HPLC. The growth hormone releasing factor was structurally characterized by gas phase sequence analysis. Reverse phase liquid chromatography of the native peptide and synthetic replicates showed that the molecule possesses an amide rather than a free acid at its carboxyl terminus. The structure of the peptide was established as: Tyr Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala -Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln -Gly-Ala-Lys-Val-Arg-Leu-NH2 using approximately 2 nmol of material.

Amino Acid Sequence↗
PubMed1983

Identification of beta-endorphin residues 14-25 as a region involved in the inhibition of calmodulin-stimulated phosphodiesterase activity.

The inhibition of the calmodulin-mediated stimulation of bovine brain cyclic nucleotide phosphodiesterase activity (3':5'-cyclic adenosine monophosphate 5'-nucleotidohydrolase, EC 3.1.4.17) by the 31-residue opiate peptide beta-endorphin has been investigated. Using conditions in which porcine brain calmodulin (6 nM) is limiting (i.e., to give a 3-fold, Ca2+-dependent stimulation of enzymic activity toward cyclic guanosine monophosphate), the domain of beta-endorphin responsible for the inhibition was mapped by using a series of deletion peptides. beta-Endorphin exhibited an ED50 of several micromolar under the conditions employed, and several amino-terminal deletion peptides were essentially as inhibitory as the parent peptide. Methionine enkephalin and various carboxy-terminal deletion peptides had no demonstrable effect at concentrations of 100-200 microM. Peptides 1-25 and 1-27 (C' fragment) inhibited the calmodulin-dependent activity of phosphodiesterase, but higher concentrations were required than of beta-endorphin. Studies using combined amino- and carboxy-terminal deletion peptides demonstrate that peptide 14-25 was the shortest peptide examined that was capable of inhibiting calmodulin stimulation of phosphodiesterase activity under the conditions used. There was no evidence to indicate that the amino-terminal region comprising residues 1-13 of beta-endorphin contributes to the measured inhibition of calmodulin-stimulated enzymic activity. The circular dichroic spectra of calmodulin, beta-endorphin, and mixtures of the two were obtained, and the ellipticity of the peptide-protein mixtures at 221 nm exceeded that expected by assuming simple additivity. This finding is consistent with a direct interaction of beta-endorphin with calmodulin which seems to lead to enhanced helicity of one or both components.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1983

Isolation and characterization of the porcine hypothalamic growth hormone releasing factor.

A 44 amino acid peptide with high intrinsic growth hormone releasing activity was isolated from 2500 porcine hypothalami by means of acid extraction, immunoaffinity chromatography, gel filtration, and 2 steps of reverse phase HPLC. The growth hormone releasing factor was structurally characterized by gas phase sequence analyses of the intact peptide and its carboxyl terminal cyanogen bromide digestion fragment. Reverse phase liquid chromatography of the native peptide and synthetic replicates showed that the molecule possesses an amide rather than a free acid at its carboxyl terminus. The structure of the peptide was established as: Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu-Gln-Gly-Ala-Arg-Val-Arg-Leu-NH2 using approximately 6 nmol of material.

Amino Acid Sequence↗
PubMed1983

In vivo biological potency of rat and human growth hormone-releasing factor and fragments of human growth hormone-releasing factor.

The biological potency of the synthetic replicates of three peptides isolated from a human pancreatic tumor with growth hormone releasing activity and rat hypothalamic growth hormone-releasing factor was evaluated in conscious freely-moving rats and anesthetized rats. All 4 peptides are equipotent on a molar basis in their ability to stimulate GH secretion. Studies with synthetic fragments of the human derived material indicated that the amino-terminal amino acid is required for activity. Deletion of as many as 13 amino acids from the carboxy-terminal failed to decrease GH-releasing activity; however, deletion of 16 amino acids resulted in a significant decrease and deletion of 20 amino acids resulted in complete loss of bioactivity.

Amino Acid Sequence↗
PubMed1983

Radioimmunoassay of human prolactin based on a 13 amino acid synthetic analog of the amino terminus.

A 13 amino acid analog of the human prolactin amino terminus was synthesized, substituting tyrosine for valine at residue 13. The peptide was coupled to crystalline bovine serum albumin for antisera production. The peptide was used for iodination with 125I, and displacement curves were found to be parallel when human prolactin and the synthetic peptide were compared as standards. The radioimmunoassay using the synthetic peptide has the advantages of purity in its roles as hapten in the antigen and as labelled peptide, of ease of iodination of the peptide, of its stability after iodination, and of obviating the need for native human prolactin. The radioimmunoassay is suitable for the measurement of human prolactin concentration in plasma.

Amino Acid Sequence↗
PubMed1983

Human hypothalamic growth hormone releasing factor (GRF): evidence for two forms identical to tumor derived GRF-44-NH2 and GRF-40.

Human hypothalamic growth hormone-releasing factor (GRF) was purified by gel filtration and reverse-phase HPLC. Bioassay and two radioimmunoassays of different specificity revealed the presence of two major forms of GRF-activity which coelute with human pancreas GRFs, hpGRF-44-NH2 and hpGRF-40 previously characterized in pancreas tumors. The bioactive material coeluting with hpGRF-44-NH2 is recognized by two antibodies which are directed against the amidated COOH-terminal sequence and the central portion of the GRF-44 peptide. The bioactive GRF which coelutes with hpGRF-40 reacts only with the antibody directed against the central portion of hpGRF. These data strongly suggest that the human hypothalamus contains the same major forms of GRF that were identified in pancreas tumors responsible for acromegaly in the absence of a pituitary tumor.

Biological Assay↗
PubMed1983

Potent interaction between glucocorticoids and growth hormone-releasing factor in vivo.

Administration of dexamethasone significantly enhanced the pituitary growth hormone response to growth hormone-releasing factor in intact as well as adrenalectomized rats. Thus the inhibitory effects of glucocorticosteroids on somatic growth which involve an interaction of these steroids and growth hormone at a peripheral level may also involve a modification of pathways within the central nervous system that regulate normal growth hormone secretion.

Adrenalectomy↗