Crude Anterior Pituitary Extract Research Articles

POMC in rhesus anterior pituitary and plasma: Evidence of N-acetylated β-endorphin and α-MSH

Pro-opiomelanocortin (POMC) related peptides have been studied in rat tissue and plasma, but they have not been well characterized in the rhesus monkey. Since monkey pituitary may be more similar to the human pituitary than the rat, we have characterized POMC related peptides by immunocytochemical, multiple radioimmunoassays (RIA's) and molecular sieving chromatography. Immunocytochemical staining demonstrated N-acetylated- β-endorphin (N-Ac- β-End) and α-MSH in a few corticotrophs. RIA's of crude anterior pituitary extract and molecular sieving chromatography demonstrates that the major portion is β-End sized with a significant proportion being N-acetylated and an α-MSH peak. Molecular sieving chromatography of extracted plasma demonstrated a similar pattern to that seen in the anterior pituitary. These data suggest that rhesus monkey processes POMC differently than rat or man.

Inhibitory effect of pituitary factor on phagocytosis and iodine metabolism in human leukocytes.

A pituitary factor decreasing iodine uptake and protein-bound iodine formation in human leukocytes was found in semi-purified preparations of TSH, LH, FSH, GH and in crude anterior pituitary extract. ACTH, insulin, serum gamma globulin, myoglobin and ceruloplasmin were ineffective in comparison to control samples incubated with serum albumin. TSH, in relation to dose (0.01–0.5 U/ml), significantly decreased the total uptake, formation, and release of iodocompounds from phagocytic leukocytes. The amount of iodocompounds released from resting or phagocytic leukocytes into the media was twice as high as the amount of organically bound iodine that remained in the cells. These data suggest that iodine-containing compounds are actively formed, metabolized, and released from human leukocytes. Because TSH also decreases engulfment of latex microparticles, the observed changes in iodine metabolism are probably secondary, due to the reduced phagocytosis. The presence of an unknown factor in the semipurified prepara...

EVIDENCE FOR A THYROID-INHIBITING FACTOR OF ADENOHYPOPHYSIAL ORIGIN.

Thyroids of normal or thyroxine ( T4)-pretreated rats were incubated in vitro in a serum medium containing I131. It was found that the addition of either a whole rat adenohypophysis, a crude rat anterior pituitary extract, or of commercial bovine thyrotrophin (TSH) to the medium caused a slight stimulation of I131 release and no apparent stimulation but rather an immediate and considerable inhibition of thyroid-I131 uptake. Preincubation of rat thyroid with crude anterior pituitary extract resulted in a prolonged inhibitory effect on the thyroid-I131 uptake. In vivo studies showed that shortly after TSH administration a similar inhibition of uptake occurred in normal rats, although allowing 24 hr for TSH stimulation brought about no change in iodine uptake in thyroids of normal and a marked increase in uptake by thyroids of T4-pretreated rats. The inhibition of thyroid-I131 uptake was assumed to have been caused either by TSH itself, or by a thyroid-inhibiting factor of adenohypophysial origin present in commercial TSH preparations as a contaminant.

An effect of anterior pituitary hormones on bovine corpus leteum phosphorylase

In vitro addition of a crude anterior pituitary extract, chorionic gonadotrophin, and growth hormone to bovine corpus luteum slices increases the amount of active phosphorylase in the tissue. Prolactin, luteinizing hormone, ACTH, follicle stimulating hormone and thyroid stimulating hormone had no significant effect on corpus luteum phosphorylase. Glucagon decreased phosphorylase activity in the corpus luteum.

Serological evidence of the antigenicity of ox anterior pituitary growth hormone in sheep.

Using the tannic acid haemagglutination test, antibodies reacting with a purified preparation of ox growth hormone were detected in the sera of sheep following injection with crude anterior pituitary extract or with purified ox growth hormone. Prior absorption of the sera with various anterior pituitary preparations rich in ox growth hormone inhibited haemagglutination. Absorption of the sera with anterior pituitary preparations containing negligible amounts of growth hormone or with ox serum did not inhibit haemagglutination. It is concluded that ox growth hormone is antigenic in the sheep.

Diabetogenic effect of growth hormone in the intact force-fed adrenocorticotrophin treated rat.

THE diabetogenic effect of both crude anterior pituitary extract and purified growth hormone in the dog and cat is now well established. Originally demonstrated with crude anterior pituitary extract, (Johns et. al, 1927, Evans, et al. 1932, Houssay, 1936, Young 1937 and Lukens and Dohan 1942) both temporary and permanent diabetes have now also been induced in dogs and cats with more highly purified preparations of growth hormone (Cotes, Reid and Young, 1949; Houssay and Anderson 1949; Campbell et al., 1950a, 1950b). As has been emphasized by Young (1944), diabetes is fairly readily precipitated in adult animals wereas in immature ones enhanced growth is the usual response to the same pituitary preparations. In the cat, the diabetogenic effects of pituitary extracts are not apparent following adrenalectomy, but may be restored if the animals are maintained on a constant dose of adrenal extract which itself does not induce glycosuria (Long and Lukens 1936).

The role of hormones in adipose glycogen synthesis in the rat; anterior pituitary growth hormone.

Anterior pituitary growth hormone exerts an influence on fat and carbohydrate metabolism in addition to its well known effect of promoting nitrogen storage and growth (Li and Evans, 1948). In the fasting animal, ketosis and an accumulation of fat in the liver occur rapidly after the injection of purified growth hormone (Bennett et al., 1948, Szego and White, 1949). The latter authors showed that the adrenal is not essential for this response. In the fasting normal, hypophysectomized or adrenalectomized rat crude anterior pituitary extract (Harrison and Long, 1940) and purified growth hormone (Milman and Russell, 1949) both produce a prolonged depression of the blood sugar. These latter observations suggest that some of the effects of growth hormone may be mediated in part by insulin. Such a viewpoint was first proposed by Mirsky in 1939 and further developed by Young (1939, 1941, 1944, 1945) and by Gaebler and Galbraith (1941) and Gaebler and Robinson (1942).

SEROLOGICAL PROTECTION AGAINST THE DIABETOGENIC SUBSTANCE OF THE ANTERIOR PITUITARY GLAND

A number of investigators have observed that, when dogs are treated with diabetogenic anterior pituitary extract, the symptoms of diabetes may make only a transitory appearance despite the daily administration of very large amounts of extract. Young [1937] found that the diabetic condition could be induced to reappear when the amount of extract injected daily was suitably increased, and did not believe that the refractory state resulted from the appearance in the blood of antihormones. However, Dohan & Lukens [1939] found that when a dog had been treated with daily injections of crude anterior pituitary extract for over 9 months, its serum possessed anti-diabetogenic activity. Administration of such serum to completely depancreatized dogs induced a marked decrease in the intensity of glycosuria. Young [1938], on the other hand, using preparations of prolactin with marked glycotropic (anti-insulin) activity, was able to produce sera with marked anti-prolactin action but with no detectable

PITUITARY-DIABETES IN THE CAT; RECOVERY FOLLOWING INSULIN OR DIETARY TREATMENT

FOLLOWING THE ANNOUNCEMENT (1) that permanent diabetes could be produced in dogs by means of anterior pituitary extract, Young (2) reported experiments in other species. He administered crude anterior pituitary extract to mice, rats, guinea pigs, rabbits and cats. Of these animals, the mouse, rat and guinea pig were “almost completely insensitive” to the diabetogenic action of the extract. Rabbits and cats showed slight and transitory glycosuria in 50 per cent or less of the animals tested, whereas all but 1 of 25 dogs developed glycosuria. In the present work the production of pituitary-diabetes in cats was undertaken, a), to learn whether the native resistance to pituitary extract could be overcome by partial pancreatectomy in this species as it had been in the rat (3) and if so, whether permanent diabetes could be produced; and, b), to develop a smaller and more economical animal than the dog for the study of this condition.

Carbohydrate Metabolism of the Chick Embryo

Summary1. Thyroxin and suprarenal cortical extract induce glycogenolysis of the glycogen normally present in the livers of 8-day embryos. 2. The injection of adrenalin in approximately physiological concentration appears to have no effect on liver glycogen. 3. Increased liver and skeletal muscle glycogen and a rise in the blood sugar level have been noted after the injection of crude anterior pituitary extract, suggesting a stimulation of gluconeogenesis. 4. Liver glycogen is increased in 8-day embryos by the injection of insulin and this increase is to be correlated with a rapid fall in the blood sugar level. 5. Injection of glucose fails to interrupt the normal disappearance of glycogen from the livers of 12-day embryos. 6. Both insulin and anterior pituitary extract cause an increase in the liver glycogen of 12-day embryos. The anterior pituitary extract also causes a rise in the blood sugar level at this time.

The influence of diabetogenic anterior pituitary extracts on the islets of langerhans in dogs

It has been shown by Young (1937, 1938) that the daily injection into dogs of large amounts of a crude anterior pituitary extract can induce, in a relatively short time, a clearly defined diabetic condition, which continues after the injections cease and becomes permanently established. These observations have been confirmed by Campbell and Best (1938) and by Dohan and Lukens (1939). An account of the histological changes in the pancreas and other organs of two dogs made permanently diabetic by treatment with crude anterior pituitary extract in this way, has already been published (Richardson and Young 1938). Nine further animals have been available for examination including several that had been treated with fractionated extracts instead of the original crude saline extract. With this additional material it has been possible to confirm and extend our original observations on the effects of the diabetogenic extract on the islets of Langerhans.

THE ANTERIOR PITUITARY GLAND AND PROTEIN METABOLISM

It has been realized for some years that treatment with anterior pituitary extract may be followed, under some conditions, by a positive nitrogen balance [Teel & Cushing, 1930; Gaebler, 1933; Lee & Schaffer, 1934] and a fall in the non-protein nitrogen content of the blood [Teel & Watkins, 1929]. As might be expected such effects are associated with growthpromoting fractions of the anterior pituitary lobe. Evidence is now accumulating which relates the influence of anterior lobe preparations on growth and nitrogen retention with their action on carbohydrate metabolism. Thus Shipley & Long [1938] and Young [1939a] found that anterior pituitary fractions which possess diabetogenic activity are also growth-promoting, while more recently Dohan, Fish & Lukens [1941] found that dogs which are in the process of being made permanently diabetic as the result of treatment with crude anterior pituitary extract, exhibit nitrogen retention during those periods in which there was

The effect of anterior pituitary extracts on established lactation in the cow

In 1928 Strieker and Grueter found that the administration of a crude anterior pituitary extract to rabbits, which had been ovariectomized during pseudopregnancy, resulted in the secretion of milk. This result was of fundamental importance as it suggested that the stimulus to the onset of lactation after parturition was the secretion of a substance by the pituitary gland, and not merely the removal of the stimuli which cause growth of the mammary gland during pregnancy. The results of Strieker and Grueter have been widely confirmed, and at the present time the theory is generally accepted that initiation and maintenance of lactation are controlled by the anterior pituitary gland. The chief evidence for this theory, which has been adequately reviewed recently by Nelson (1936), is, briefly, that normal lactation does not occur spontaneously in the absence of the pituitary gland, although the secretion of milk may, in suitable circumstances, follow the administration of anterior pituitary extracts to normal or hypophysectomized animals.