Anterior Pituitary Extract Research Articles

Effect of anterior pituitary preparations on rat mammary gland growth.

SummaryUsing desoxyribosenucleic acid (DNA) as an index of mammary gland growth, crude and purified anterior pituitary extracts were tested for mammary gland growth promoting (mammogenic) effectiveness. Acetone dried AP powder and an initial extract of AP were shown to be effective in stimulating production of mammary gland DNA. Initial residue, Mammogen “A” and “C”, shown previously to produce mammary gland growth in mice, were found to be ineffective in rats. Fractions rich in lactogen and growth hormone were found to be minimally effective in stimulating mammary gland lobule-alveolar growth.

The application of the technique of egg transfer to sheep breeding

During the autumns of 1960 and 1961, 86 first- and second-cross (backcross to polled rams) polled Merino ewes were treated with a horse anterior pituitary extract (HAP) to induce multiple ovulation. Of the 86 ewes, 78 were served within 96 hr of the cessation of treatment. Laparotomies, performed for the pqrpose of egg recovery, showed that 74 of the ewes served had ovulated, shedding a total of 841 eggs of which 667 were recovered and of these 482 had been fertilized. A total of 441 fertilized eggs were transferred at rates of one to three per animal to the uterine horns or Fallopian tubes of 262 recipient horned Merino ewes of which 177 subsequently lambed, producing 236 lambs. Irrespective of the number transferred per recipient, the proportion of eggs which developed into lambs following tuba1 transfers was significantly less than that following uterine transfers. The survival of transferred eggs was not significantly affected by the number transferred per recipient. The practical value of the technique of egg transfer in the ewe is briefly discussed.

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.

The maintenance of lactation in the goat after hypophysectomy.

SUMMARY Five adult goats were hypophysectomized during lactation; within 10 days their milk yields dropped to a fifth or less of the preoperative levels. The daily milk yield of one of these goats was increased from 10 to 288 ml. by giving daily injections of ox anterior-pituitary extract; the yield of a second goat was increased from 110 to 1315 ml. by daily injections of sheep anterior-pituitary extract. Treatment of the three other goats with purified anterior-pituitary hormones, corticoids, insulin and triiodo-l-thyronine increased their milk yields from 230, 10 and 45 ml./day to 1480, 1320 and 270 ml./day, respectively. Milk secretion was induced in the right udder-half of a sixth animal—which had been hypophysectomized in mid-pregnancy and had aborted—by the local injection of prolactin into the parenchyma of the right udder-half plus the systemic injection of somatotrophin; general lactation was subsequently induced and maintained by systemic treatment with prolactin, somatotrophin, adrenocorticotrophin, corticoids, insulin and triiodo-l-thyronine. The maximum daily yield of the animal was 625 ml. Prolactin and somatotrophin appear to be major components of the lactogenic and galactopoietic complexes in the goat, but further study is required to determine their relative importance and to confirm a preliminary observation that lactation may proceed in the hypophysectomized goat at least for a time by treatment with hormone combinations which include somatotrophin but not prolactin. A marked increase in water intake of one hypophysectomized goat appeared to be associated with the administration of somatotrophin. The possibility of species specificities existing in relation to prolactin are discussed.

Precorticotrophin in blood.

THE existence of precorticotrophin, precursor of corticotrophin, has been demonstrated by Dasgupta and Young1. Extracts of ox anterior pituitary, otherwise inactive, acquire a corticotrophic activity detectable by Sayers' test (adrenal ascorbic acid depletion) when the medium is acidified (pH 3) or when urea (3–8 M) is added to it. These findings have been confirmed by Dixon et al.2, who observed the presence of precorticotrophin in pig pituitary also (personal communication). Earlier, Moruzzi et al.3 reported the presence of an ‘inactive’ form of corticotrophin (activable by treatment with oxycellulose) in the blood of patients suffering from various types of adrenal insufficiency, including Addison's disease; they called it ‘activable’ corticotrophin. The possibility that ‘precorticotrophin’ may be comparable with ‘activable’ corticotrophin and that the former may be in circulation even under normal physiological conditions was discussed by Dasgupta4. The present report is concerned with the actual demonstration of precorticotrophin in normal rabbit blood.

The production and cure of metahypophyseal diabetes in the cat: a biochemical and electron-microscopical study with particular reference to the changes in the islets of Langerhans of the pancreas

The induction of metahypophyseal diabetes in the cat by treatment with ox anterior pituitary extract, or purified ox pituitary growth hormone, and its cure by treatment with the anti-diabetic sulphonamide, tolbutamide, is described. The fine structure and histochemistry of the pancreatic islets were investigated during the course of the diabetes and after recovery from it, by the examination of biopsy specimens. During the induction of the diabetes theβcells were denuded of their specific secretory granules and became progressively disorganized and dilated by the presence of intracellular glycogen. In those animals which had recovered from diabetes theβcells of the pancreatic islets contained a nucleus, mitochondria, Golgi membranes, and a normal complement of secretory granules and endoplasmic reticulum. In animals which did not recover from diabetes theβcells of the pancreatic islets had been destroyed. Recovery from diabetes is associated with a substantial increase in the number of cytoplasmic ribonucleic acid particles in theβcells, and also by a great expansion in the surface area of the endoplasmic reticulum. The secretory granules reappear in the Golgi region in the recoveredβcells.

Effect of graded doses of anterior pituitary extract on thyroid weight and thyroid/serum iodide ratio in the hypophysectomized rat.

Journal Article EFFECT OF GRADED DOSES OF ANTERIOR PITUITARY EXTRACT ON THYROID WEIGHT AND THYROID⁄SERUM IODIDE RATIO IN THE HYPOPHYSECTOMIZED RAT Get access Endocrinology, Volume 66, Issue 2, 1 February 1960, Pages 306–307, https://doi.org/10.1210/endo-66-2-306 Published: 01 February 1960 Article history Received: 27 July 1959 Published: 01 February 1960

Uptake of 35S-labelled sulfate in the harderian and the ventral lacrymal glands of the guinea pig during stimulation with ophthalmotrophic pituitary agents; a new assay method for ophthalmotrophic activity in thyrotrophic preparations.

Albert (1945) observed that the exophthalmos producing activity in anterior pituitary extracts of sheep paralleled only the thyroid stimulating activity. In addition preparations of follicle stimulating hormone and luteinizing hormone which produced exophthalmos also caused hyperplasia and hypertrophy of the thyroid. It has been demonstrated (Dobyns & Rawson, 1951) that the thyroid stimulating as well as the exophthalmic principle in thyrotrophic pituitary extracts are inactive after incubation of the extract with explants of thyroid tissue. The exophthalmic and the thyroid stimulating principles do not always accompany each other. It has been reported by Jefferies (1949) that following iodination of a pituitary extract the thyroid stimulating material became 1. Aided by grants from the Danish State Research Foundation, the Danish Rheumatism Association, and the Sigrid Juselius Stiftelse, Finland. Facilities of the Carlsberg Laboratorium, Copenhagen, were employed for some of the experiments. 2. Present address: Fellow of the Rockefeller Foundation at the College of

The pituitary and the maintenance of milk secretion.

Following the demonstration by Strieker & Grüter (1928) of the lactogenic effects of anterior-pituitary extracts, the importance of the role of the pituitary in maintaining lactation was further emphasized by observations that removal of the pituitary in the lactating animal resulted in a rapid and complete cessation of lactation (for references, see Folley 1952). For a time it was generally assumed that the loss of the anterior pituitary was the causal factor in the cessation of lactation, but when the role of the posterior pituitary in milk ejection was established it became obvious that interference with the milk-ejection reflex could well be the cause of the failure of lactation after hypophysectomy. It therefore seemed desirable to repeat some of the earlier studies on the effect of hypophysectomy on lactation, in order to determine whether the restoration of milk-ejection by the regular administration of oxytocin would affect the results and possibly allow us to distinguish a failure of milk ejection from a failure of milk secretion. In this connexion it may be noted that reports on the maintenance of lactation after hypophysectomy, by administering anterior-pituitary preparations, have been remarkably few, and this lack of information possibly reflects the unsuccessful outcome of attempts which may have failed because milk ejection was not restored. At Shinfield we have studied the effect of hypophysectomy in the lactating rat, both in the presence and absence of adequate oxytocin therapy, and have confirmed that hypophysectomy results in a rapid and complete inhibition of milk secretion (see Cowie 1957), and there seems to be no reason to doubt that this will also be true for other species.

Effect of adrenocortical and hypophyseal hormones on uptake of fat by isolated perfused liver.

The effect of adrenocortical and anterior pituitary hormones on the uptake of neutral fat by the perfused rat liver has been investigated. It was observed that adrenalectomy increased the rate of fat uptake. Cortisone treatment of adrenalectomized animals reduced the rate of fat uptake to that of the normal fed state. Cortisone and hydrocortisone administered in vivo, or added to the perfusion fluid in vitro, reduced the rapid rate of fat uptake resulting from 48 hours of fasting. Hydrocortisone administered to normal fed rats did not depress the rate of fat uptake. The administration of crude anterior pituitary extracts to the normal fed animal significantly increased fat uptake. Hypophysectomy increased the rate of fat uptake. Administration of growth hormone to the normal fed animal 3–8 hours prior to killing, or added to perfusion fluid in vitro, increased the rate of fat uptake.

Effects of crude pituitary extracts on glucose utilisation by isolated rat diaphragm

When isolated rat diaphragm is incubated for a short time with an anterior pituitary extract, and is then transferred to a second medium containing glucose in which it is incubated for a longer time, one of two effects on the glucose uptake may be manifested. 1. 1. With undiluted or diluted extracts, the response of the muscle to insulin, when this is added to the second incubation medium, is suppressed. 2. 2. With diluted extracts, the uptake may be raised significantly above the uptake of diaphragm which has been incubated in medium alone. Insulin, when added to the second incubation medium, does not raise the uptake further. These two effects may be explained in terms of the known growth-hormone content of the extracts, and of the high content of haemoglobin in them. It has been shown that preliminary incubation of the diaphragms with haemoglobin, but probably not methaemoglobin, will suppress their response to insulin in a subsequent incubation period (effect I above). It is suggested that this is probably due to carry-over of haemoglobin in the extracellular fluid of the muscle, which forms an insoluble complex with insulin. It has been shown that a mixture of purified growth hormone and purified haemoglobin in the concentrations ordinarily present in crude extracts of the anterior pituitary, stimulates the effects of these extracts on the isolated diaphragm. The results suggest that in some of the extracts there may have been a third, inhibitory factor. No conclusions could be drawn about its origin.

Degradation of insulin- I 131 by an extract of anterior pituitary gland.

When insulin-I131 was incubated at 37°C and pH 7.5 with an extract of beef anterior pituitary, the radioactive material was rendered more soluble in trichloroacetic acid (TCA). Electrophoretic analysis of the TCA-soluble reaction product revealed that it was not free iodide. The concept that pituitary extract might contain a system capable of attacking the insulin molecule was strengthened by the observation that the addition of nonlabeled insulin to the incubation mixture decreased the rate of degradation of insulin-I131. The degradative system of beef anterior pituitary extract was found to be nondialyzable and heat-labile. The degradation of insulin by pituitary extracts may help to explain the observation of other workers that such extracts can inactivate insulin in vitro.

On the Nephrosclerotic Potency of Purified Anterior Pituitary Extracts

On the Nephrosclerotic Potency of Purified Anterior Pituitary Extracts

Decreased insulin requirement following growth hormone administration in diabetic dogs.

IT HAS long been known that during injections of diabetogenic anterior pituitary extracts the severity of diabetes in metahypophyseal-diabetic and depancreatized dogs is increased (1); but it is not so well established that subsequently the insulin requirements of these dogs are decreased to less than the initial levels for considerable periods of time (2). These effects are now shown to be exerted by purified growth hormone. The influences of repeated treatments with growth hormone and of variations in the insulin dosage have been studied, and the effects of deprivation of insulin and of adrenocorticotropic hormone (ACTH) have been compared to the effects produced by the growth hormone. Physiological implications of the results have already been indicated (3). methods and materials The methods used, for the analysis of blood and urine have been described previously (4). The crystalline bovine growth hormone (Campbell and Davidson, 5) was apparently homogeneous by ultracentrifugal and electrophoretic anal...

FURTHER STUDIES ON THE ENDOCRINE CONDITIONING OF THE HEPARIN-INDUCED LIPEMIA CLEARING ACTIVITY (LCA) IN THE RAT

The effects of various endocrines and of stress on the "lipemia clearing activity" (LCA) which is elicited in rat plasma by intravenous heparin injection were studied.High dosage cortisone accelerated LCA, but low dosage cortisone did not affect it. Severe catabolic stress accelerated LCA. Application of a single mild stress was ineffective, but the combination of two mild stressors accelerated LCA. ACTH had no influence on LCA, but adrenalectomy accelerated it. Stilbestrol inhibited LCA at both a low and a high dosage level, but there was no difference in LCA production between males and females or between estrous and diestrous females. Estrous females, however, displayed less LCA than ovariectomized females. Anterior pituitary extract inhibited LCA in females and hypophysectomy accelerated it in both sexes. A synthetic oil emulsion yielded the same qualitative information as lipemic plasma wherever it was used as a substrate for the clearing activity of postheparin plasma.Thus, with the exception of the effects of sex difference and low dosage cortisone, most of the previously reported endocrine effects on the LCA that follows subcutaneous heparin were also obtained when heparin was injected intravenously. The physiological significance of these findings is discussed.

Lipid mobilizer (LM) from posterior pituitary of hogs.

1. Dialyzate of hog posterior pituitary lobe induced hyperlipemia in rats, mice, guinea pigs, dogs and rabbits. 2. The LM activity was indistinguishable from that of plasma dialyzate from cortisonized animals. 3. Neither Pitressin® nor Pitocin® had LM activity. 4. Hog anterior pituitary extracts had no LM activity. 5. LM appears to be a hitherto undescribed hormone either elaborated or stored in the posterior pituitary.

The subcutaneous assay of corticotrophin A.

Since the introduction of corticotrophin (ACTH) into therapy in 1949 the hormone has usually been assayed by the ascorbic acid depletion method of Sayers et al. (1948), in which the fall in the concentration of ascorbic acid in the adrenals of hypophysectomized rats is a linear function of the logarithm of the dose ACTH, given intravenously. In therapy, however, corticotrophin is, as a rule, given subcutaneously or intramuscularly and only occasionally intravenously as a continuous infusion. In recent years clinical and experimental observations were made which demonstrated that the expected potency of ACTH-preparations did not always equal their clinical effect, when injected extravascularly, i. e. subcutaneously or intramuscularly. The therapeutic value of corticotrophin preparations obtained by different chemical procedures varied from 25 % to about 300 % of that expected from the determination of potency by the ascorbic acid depletion method. However, if used for continuous intravenous infusion, no variation in the clinical effect from the labelled potency greater than that within the error of the assay itself could be observed. These findings are extensively discussed by Wolfson (1953) and Fisher et al. (1953). Wolfson distinguishes three main types of corticotrophin: Crude corticotrophin (the first international corticotrophin standard La-l-A; the U. S. P. corticotrophin reference standard), which chemically is a glacial acetic acid extract of anterior pituitary of mammals. Corticotrophin A (ACTX, purified corticotrophin, high-potency corticotrophin, Type I-purified ACTH of Thompson and Fisher), which chemically is crude corticotrophin purified by adsorption on oxycellulose and subjected to little or no acid or peptic hydrolysis. Corticotrophin B (Actide corticotrophin), which is prepared by the use of acid or peptic hydrolysis or both.

Hormonal factors influencing calorigenesis.

IT IS well established that the thyroid is the gland controlling respiratory metabolism; that the thyroid in turn is controlled by a specific hormone of the anterior pituitary is equally well accepted. However, several reports have appeared which suggest that increase in metabolic rate can be obtained by pituitary extracts without thyroid mediation. Lactogenic hormone was reported to increase heat production in thyroidectomized as well as hypophysectomized birds (1). Growth hormone preparations were reported to increase the metabolic rate of thyroidectomized mammals (2, 3, 4). Evidence has been presented by Collip and his associates for a specific metabolic factor in anterior pituitary extracts other than thyrotrophic hormone (5, 6, 7). A calorigenic action from adrenocorticotrophic fractions has been reported by Astwood and others (8–14). Erythropoietically active pituitary fractions have been reported to restore the low metabolic rate of hypophysectomized and of thyroidectomized rats (15). A reexaminati...

The Metabolic Effects of Growth Hormone and Their Physiological Significance

Publisher Summary The participation of the pituitary gland in the regulation of body growth was implicated a number of years ago on the basis of clinical observations. Thus, on the basis of pathological findings, acromegaly and dwarfism have been attributed to a hyperfunction and hypofunction of the anterior pituitary gland, respectively. The first experimental evidence for this pituitary function was provided by the classical studies of Aschner, who produced dwarfism by the removal of the pituitary gland from puppies. This observation was subsequently confirmed and extended in tadpoles and rats. A further great advance in relating the pituitary gland to growth was attained by Evans and Long, who produced gigantism in normal rats by long-continued daily administration of saline extracts of ox anterior pituitary. These findings were further advanced by Smith, who showed that the impairment of growth in hypophysectomized animals could be rectified by daily implants of the anterior pituitary or pituitary extracts. In the chapter, the effects of growth hormone on protein, fat, and carbohydrate metabolism are reviewed and the physiological significance of the interrelationship of these effects is discussed.

FURTHER STUDIES ON THE ENDOCRINE CONDITIONING OF THE HEPARIN-INDUCED LIPEMIA CLEARING ACTIVITY (LCA) IN THE RAT

The effects of various endocrines and of stress on the "lipemia clearing activity" (LCA) which is elicited in rat plasma by intravenous heparin injection were studied.High dosage cortisone accelerated LCA, but low dosage cortisone did not affect it. Severe catabolic stress accelerated LCA. Application of a single mild stress was ineffective, but the combination of two mild stressors accelerated LCA. ACTH had no influence on LCA, but adrenalectomy accelerated it. Stilbestrol inhibited LCA at both a low and a high dosage level, but there was no difference in LCA production between males and females or between estrous and diestrous females. Estrous females, however, displayed less LCA than ovariectomized females. Anterior pituitary extract inhibited LCA in females and hypophysectomy accelerated it in both sexes. A synthetic oil emulsion yielded the same qualitative information as lipemic plasma wherever it was used as a substrate for the clearing activity of postheparin plasma.Thus, with the exception of the effects of sex difference and low dosage cortisone, most of the previously reported endocrine effects on the LCA that follows subcutaneous heparin were also obtained when heparin was injected intravenously. The physiological significance of these findings is discussed.