INHIBITION BY HUMAN SERUM OF THE ADIPOKINETIC EFFECT OF A HUMAN PITUITARY LIPID-MOBILIZING FACTOR (LMF) IN RABBITS

1967 ◽  
Vol 56 (4) ◽  
pp. 649-660 ◽  
Author(s):  
Olav Trygstad ◽  
Irene Foss

ABSTRACT A lipid-mobilizing factor (LMF) has previously been prepared from human pituitary glands. The LMF was strongly adipokinetic in rabbits. Subcutaneous injection of 0.1 mg gave an increase of serum nonesterified fatty acids (NEFA) in the range of 5 meq./l. Addition of 3 ml normal human serum to LMF reduced its adipokinetic effect. The inhibition of LMF by human serum was specific, since serum from mouse or pig did not reduce the increase of serum NEFA induced by LMF, and human serum had no influence on the adipokinesis given by whale, pig, or synthetic ACTH preparations in rabbits. The human serum inhibition of LMF was located to the gamma G globulin fraction by DEAE-cellulose chromatography. Serum from six children with generalized lipodystrophy had a negligible influence on the adipokinesis in rabbits induced by LMF. Sera from one group of obese patients reduced the adipokinetic effect of LMF as normal control sera, while sera from another group of obese patients made the increase of serum NEFA negligible. It is suggested that the first group of obese patients may be related to Mayer's simple regulatory or 'hyperphagic' type of obesity and the latter to his metabolic type of obesity. Furthermore possible mechanisms for the human serum inhibition of LMF are discussed.

1972 ◽  
Vol 71 (3) ◽  
pp. 443-453 ◽  
Author(s):  
Olav Trygstad ◽  
Irene Foss

ABSTRACT A lipid-mobilizing factor (LMF) with an adipotrophic effect in human and animal fat tissue has been prepared from human pituitary glands. The addition of normal human serum to LMF reduced its lipolytic effect, and it was completely abolished by serum from a group of obese patients, whereas the lipolysis was not influenced by serum from patients with generalized lipodystrophy. By DEAE-cellulose chromatography of human serum the inhibitory effect on LMF was found to be present in a protein fraction less acidic than the main serum albumin fraction. The inhibitory fraction was deprived of some contaminants by Sephadex gel filtration. Disc electrophoresis demonstrated the presence of three components in the inhibitory protein (IP), and they were identified as albumin, transferin, and haemopexin by immuno-electrophoresis. Precipitation of these proteins by their rabbit antisera demonstrated that the inhibitory effect was present in the albumin fraction. Insulin like activity was not observed in IP. A protein binding of LMF by IP could not be demonstrated. Incubation at 37°C for one hour of a mixture of LMF and IP eliminated the electrophoretic picture of LMF. It is concluded that the inhibitory effect of human serum may be due to proteolysis of LMF.


1964 ◽  
Vol 29 (3) ◽  
pp. 263-271 ◽  
Author(s):  
G. ILLEI ◽  
PAMELA M. MORITZ

SUMMARY Antisera were raised to human chorionic gonadotrophin (HCG) and human menopausal gonadotrophin (HMG). Normal human serum and human pituitary and chorionic gonadotrophins reacted with both antisera in immunological experiments. After absorption with human serum, the γ-globulin fractions of the antisera were isolated, and only the reaction to the hormone preparations remained. Immunoelectrophoresis revealed a common antigenic factor in the α2-β globulin region. The γ-globulin fraction of HCG antiserum seems to be suitable for the assay of HCG, while that of the HMG antiserum might be employed for the detection of HMG.


1982 ◽  
Vol 99 (2) ◽  
pp. 174-178 ◽  
Author(s):  
Burt Sharp ◽  
Shlomo Melmed ◽  
Ronald Goldberg ◽  
Harold E. Carlson ◽  
Samuel Refetoff ◽  
...  

Abstract. Using a sensitive and precise radioimmunoassay for human β-endorphin, we have demonstrated the sustained secretion of opioid peptides from human pituitary tumour cells. Pituitary tumour tissue obtained from a patient with Nelson's syndrome was maintained in continuous monolayer culture and secreted both β-lipotropin and β-endorphin, with predominance of the latter. This is compatible with the idea that the β-endorphin in normal human serum is secreted as such despite the predominance of β-lipotropin compared with β-endorphin in the anterior pituitary.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhiyu Xi ◽  
Pamela S. Jones ◽  
Masaaki Mikamoto ◽  
Xiaobin Jiang ◽  
Alexander T. Faje ◽  
...  

Human pituitary adenomas are one of the most common intracranial neoplasms. Although most of these tumors are benign and can be treated medically or by transsphenoidal surgery, a subset of these tumors are fast-growing, aggressive, recur, and remain a therapeutic dilemma. Because antibodies against immune checkpoint receptors PD-1 and CLTA-4 are now routinely used for cancer treatment, we quantified the expression of mRNA coding for PD-1, CLTA-4, and their ligands, PD-L1, PD-L2, CD80, and CD86 in human pituitary adenomas and normal pituitary glands, with the ultimate goal of exploiting immune checkpoint therapy in aggressive pituitary adenomas. Aggressive pituitary adenomas demonstrated an increased expression of PD-L2, CD80, and CD86 in compared to that of normal human pituitary glands. Furthermore, aggressive pituitary tumors demonstrated significantly higher levels of CD80 and CD86 compared to non-aggressive tumors. Our results establish a rationale for studying a potential role for immune checkpoint inhibition therapy in the treatment of pituitary adenomas.


1969 ◽  
Vol 60 (1) ◽  
pp. 157-172 ◽  
Author(s):  
B.-A. Lamberg ◽  
J. Ripatti ◽  
A. Gordin ◽  
H. Juustila ◽  
A. Sivula ◽  
...  

ABSTRACT The simultaneous occurrence of acromegaly, hyperthyroidism and hyperparathyroidism is extremely rare and even that of acromegaly and hyperparathyroidism very unusual. Chromophobe adenomata producing either acromegaly, Cushing's syndrome or hyperthyroidism have been described in a limited number of cases. A unique case of a patient with acromegaly, hyperthyroidism and hyperparathyroidism and a chromophobe pituitary adenoma was studied. In the blood an unusually high level of thyrotrophin (TSH) was found (about 2 mU/ml) but no »long-acting thyroid stimulator« (LATS). The TSH activity remained unaffected by thyroidectomy and by treatment with triiodothyronine but was not found in the blood after surgical hypophysectomy. The pituitary tumour contained TSH only about 20 mU/209 mg weight of tissue, i. e. less than is found in normal human pituitary glands. There was evidence of inadequate secretion of corticotrophin and gonadotrophins. The evidence suggests that both the acromegaly and the hyperthyroidism were caused by increased production of growth hormone (STH) and TSH by the pituitary tumour. The hyperparathyroidism was due to a parathyroid adenoma. In four other acromegalic but euthyroid patients no TSH or LATS activity could be detected in the blood. In these patients the protein-bound iodine (PBI), free thyroxine and triiodothyronine-Sephadex uptake tests were normal. In addition in one of these patients, hyperparathyroidisni due to a parathyroid adenoma was observed. The occurrence of a parathyroid adenoma in acromegaly may be one facet of the multiple endocrine adenoma syndrome. In all 5 subjects the hydroxyproline in serum and urine was increased.


1973 ◽  
Vol 72 (2) ◽  
pp. 226-234 ◽  
Author(s):  
Olav Trygstad ◽  
Irene Foss

ABSTRACT A lipid mobilizing factor (LMF) with an adipotrophic effect in man and animal adipose tissue has been prepared from human pituitary glands. In vitro studies have demonstrated that the lipolytic effect was dependent on the albumin used in the incubation medium. Two of the six albumins studied depressed the release of non-esterified fatty acids from human fat pads. Polyacrylamide gel disc-electrophoresis demonstrated the presence of contaminations in purchased serum albumins. They were eliminated by DEAE-cellulose chromatography, which gave one fraction that inhibited the adipokinetic effect of LMF, and a more homogeneous albumin fraction. In vitro lipolysis in rabbit as well as in human fat pads occurred more readily in the media containing purified serum albumin than in media with purchased serum albumin. It was concluded that in vitro lipolysis gives comparable results when studied in media containing the same batch of serum albumin only. Furthermore an agent should not be claimed to be non-lipolytic until it has been assayed in several, preferably homogeneous serum albumin media.


1968 ◽  
Vol 40 (2) ◽  
pp. 165-173 ◽  
Author(s):  
M. R. SAIRAM ◽  
H. G. MADHWA RAJ ◽  
N. R. MOUDGAL

SUMMARY The follicle-stimulating hormone (FSH) inhibitor in monkey urine was purified by selective extraction of the crude extract with acetate buffer, ammonium sulphate precipitation and DEAE-cellulose chromatography. The purified inhibitor was free of luteinizing hormone activity. It behaved as an apparently homogeneous protein. The inhibitor contained about 20% carbohydrate (hexoses, hexosamines, fucose and sialic acid). Thin-layer gel filtration indicated a molecular weight of about 65,000. The inhibitor was labile to heat treatment, exposure to extremes of pH and denaturing agents. The inhibitor effectively neutralized the biological activity of FSH preparations from human, monkey, horse, pig, sheep and rat pituitary glands, pregnant mare serum gonadotrophin and human pituitary urinary gonadotrophin.


1968 ◽  
Vol 57 (1) ◽  
pp. 81-108 ◽  
Author(s):  
Olav Trygstad

ABSTRACT Clinical observations and endocrinological research have provided evidence of the existence of a specific pituitary regulation of triglycerideolysis in depot fat. A lipid-mobilizing fraction was prepared from deep-frozen human pituitary glands by slightly alkaline extraction followed by acetone precipitation at a pH below the isoelectric point for growth hormone. This crude fraction was purified by Sephadex gel filtration and DEAE-cellulose chromatography. Preparation of this lipid-mobilizing fraction failed when acetone-dried pituitary glands were used. The obtained lipid-mobilizing factor (LMF) had two bands on polyacrylamide gel disc electrophoresis, and the molecular weight was determined to be in the range of 5000. There was loss of lipolytic activity when partly purified LMF was incubated in physiological saline at 37° C. No somatotrophic or thyrotrophic activity was observed in LMF and only traces of prolactin, ACTH- and MSH-like activities. The LMF was lipolytic both in vivo and in vitro on rabbit and human adipose tissue. The effect on mouse and rat was questionable. In rabbits LMF also caused ketonaemia, hyperlipaemia, increased liver fat, decrease of liver glycogen, prolonged hyperglycaemia and decrease of serum calcium and inorganic phosphorus. High doses of LMF induced a hypermetabolic state in the rabbit with marked hypocalcaemia usually accompanied by convulsions and death. It is concluded that the prepared LMF is probably an aggregation of a lipotrophic and a rabbit serum-calcium-lowering factor. The lipotrophic factor may be a specific pituitary 'adipotrophin' or a denaturation product from a previously accepted pituitary hormone. A possible relationship between LMF and a diabetogenic-adipokinetic core of growth hormone is discussed.


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