Anterior Lobe Extracts Research Articles

Hyperglycemia and Increased Liver Glycogen Values in Hypo-physectomized Rats on Chronic Administration of Adrenocorticotropic Hormone.

Previous work from this laboratory has shown that the injection of small amounts of suitable anterior lobe extracts into 24-hour fasted hypophysectomized rats prevents the abnormal fall of muscle glycogen without affecting the blood glucose or liver glycogen.1 To produce this effect the extract is given only during the fasting period, and the presence of the adrenals is not necessary. Further investigation has shown that this acute effect is not due to adrenocorticotropic hormone.2 The present investigation is concerned with the effects of more chronic injection of adrenocorticotropic hormone. The extracts were prepared according to the method of Lyons,3 and all chemical and operative procedures were carried out as reported previously.1In Table I are summarized various experiments dealing with 10-24 days injection of BA-2 (adrenocorticotropic hormone) and a purified lactogenic preparation. For the sake of convenience these experiments are called maintenance (injections started immediately after hypophysec...

Failure of Ant. Pituitary Extracts to Maintain Fasting Carbohydrate Levels of Hypophysectomized Rats After Preliminary Treatment.

Crude anterior lobe extracts are able to maintain the fasting muscle glycogen levels of hypophysectomized rats in an acute test, but are unable to do so when injected chronically. Continued treatment of normal rats with such extracts abolishes their ketogenic effect.

Hypophyseal Thyrotropic Mechanism Essential for Occurrence of Diabetes Insipidus in its Maximal Form.

The contention that d.i. does not occur in the absence of the pars anterior of the hypophysis has been supported by a number of recent investigations.1 Views differ, however, as to the mechanism of action of the pars anterior in this respect. Barnes and Regan2 and Biasotti3 on the basis of their failure to obtain the usual diuretic effect of anterior lobe extract on thyroidectomized dogs suggested that this diuretic effect was by the thyroids through the hypophyseal thyrotropic principle. Mahoney and Sheehan's4 elimination of d.i. by thyroidectomy strongly suggested that the polydipsia and poly-uria of d.i. is dependent upon thyroid action. This concept has been questioned, to a lesser degree, by Gaebler5 and White and Heinbecker6 on the basis of their failure to duplicate in all respects Barnes and Regan's and Biasotti's results with anterior lobe extracts and more vigorously by Fisher and Ingram7 on the basis of their not being able to duplicate, with cats, Mahoney and Sheehan's results on the dog.Even ...

OBSERVATIONS ON CARBOHYDRATE METABOLISM FOLLOWING IRRADIATION OF THE PITUITARY LAND

Various investigators have presented evidence to show that the hypophysis plays an important role in carbohydrate metabolism. Houssay (1) and his coworkers were the first to show that extracts of the anterior lobe of the hypophysis, when injected into normal dogs, produce hyperglycemia, glycosuria and ketonuria (2). Furthermore, these extracts, when given in high doses, inhibit dextrose utilization and a diabetic condition is produced. The ablation of the pituitary leads to hypersensitivity to insulin, hypoglycemia, convulsions during fasting, and an increase of dextrose tolerance (3, 4). All these findings have received adequate confirmation. In depancreatized dogs the removal of the hypophysis restores carbohydrate metabolism to an approximately normal condition but on the other hand renders the animal hypersensitive to insulin (5, 6). The injection of the anterior lobe extracts to the depancreatizedhypophysectomized animal causes a reappearance of the symptoms of diabetes. This subject has been reviewed in full by Houssay (7). Since the removal of the hypophysis decreases the symptoms of experimental diabetes, it has been advocated that destructive doses of roentgen ray to the hypophysis might produce similar results in clinical diabetes. Studies in carbohydrate metabolism, usually by simple dextrose tolerance curves in patients with diabetes mellirus before and after irradiation, have been made in the past by Selle, Westra and Johnson (8, 9), and Hutton (10). These investigators found little or no changes in dextrose tolerance after irradiation and there was no increased sensitivity to insulin.

Influence of Extracts of Anterior Lobe of Pituitary on Glucose Oxidation and Glycogen Storage

SummaryRats fasted for 24 hours, when injected intraperitoneally with one cc. of anterior lobe extract shortly before glucose feeding, show a marked decrease in the amount of carbohydrate oxidized and a corresponding increase in the amount of glycogen deposited in liver and muscles, when compared with control rats treated exactly alike and injected with 1 cc. of heat-inactivated extract.

THE EFFECTS OF THYROIDECTOMY, CASTRATION, ANTERIOR LOBE ADMINISTRATION AND PREGNANCY UPON EXPERIMENTAL DIABETES INSIPIDUS IN THE CAT

In a series of papers dealing with the experimental production of polyuria in cats and monkeys (1, 2, 3) evidence has been presented to show that permanent polyuria as produced in such forms is associated with lesions interrupting the nervous pathway extending from the nucleus supraopticus to the posterior hypophysis. In these cases there is atrophy of the supraoptic nuclei and of the pars nervosa of the hypophysis, and such atrophic glands have been found to be deficient in content of antidiuretic, pressor and oxytocic principles (4). It has been further shown that polyuria may occur in cats following direct removal of the posterior lobe including the stalk, providing functional anterior lobe tissue is left (5). Cats with diabetes insipidus, or even a latent tendency that way due to partial interference with the supraoptico-hypophyseal system, are unusually sensitive to the diuretic effects of thyroid and salt feeding, but thyroidectomy, while diminishing the intensity of the polyuria, has not in our experience completely eliminated the excessive water exchange (6). The present communication deals with further experiments on the effect of thyroidectomy upon cats with diabetes insipidus, and with other observations on the influence of castration, administration of a crude anterior lobe extract and pregnancy.

HORMONAL FACTORS INVOLVED IN PARTURITION IN THE RAT

Certain theories which have been suggested to explain the onset of parturition on a hormonal basis were tested by the injection of various hormones and hormone combinations. It was thought that if the average length of the gestation period could be shortened significantly as compared with a large group of controls, this would be evidence that the hormone producing such results was involved in normal parturition. 361 rats, exclusive of controls, were used. The theories tested, and the results obtained, follow.1. Theory.—Parturition occurs as the result of an increased concentration of estrin late in pregnancy. Results.—Large doses of estrin terminate pregnancy by killing the fetuses. Doses which do not have this effect do not significantly affect the gestation period.2. Theory.—Parturition occurs as the result of the sensitization of the uterus to pitocin by estrin. Results.—No evidence supporting this theory was discovered.3. Theory.—The anterior lobe of the pituitary is involved, either directly or by stimulating estrin secretion in the follicles. Results.—Large doses of anterior lobe extract delay parturition. The fetuses die eventually and are either aborted or resorbed. Smaller doses, either with or without pitocin, have no effect.4. Theory.—Some substance in follicular fluid, placentæ, or blood is responsible. Results.—No such substance could be demonstrated.

PROPERTIES OF ANTERIOR LOBE EXTRACTS

The physiological effects which may be produced by anterior lobe extracts vary greatly both qualitatively and quantitatively, depending upon the type of gland tissue extracted, the method of handling of the tissue prior to extraction, the solvent used in making the extracts, the extent to which fractionation of the original extract has been carried out, and many other factors, of which pH and temperature are of first importance. It is my purpose in this communication to report on results obtained in a series of experiments designed to determine the effect of pH and temperature upon the potency of anterior lobe extracts prepared from dissected hog glands.

EFFECTS OF CHRONIC IMPLANTATION OF RATS WITH PITUITARIES OF THE SAME SPECIES1

Since the work dealing with the loss of sensitivity to hypophyseal extracts exhibited by animals after chronic administration has been reviewed recently by others we shall not attempt to cite all of the publications concerned with this subject. The cause of the production of this insensitivity is at present controversial. In the main, two explanations have been advanced. The one, postulated by Collip (1), that the refractoriness is a normal reaction in which antihormones hold in balance the activity of the internal secretions, is supported by the following evidence. First, the function of the gonads and thyroids of animals which have become insensitive to gonadotropic and thyrotropic extracts of anterior lobes of a different species is depressed below normal, indicating perhaps a neutralization of the animal's own pituitary hormone (2, 3, 4, 5, 6, 7, 8). In line with this is the evidence that the serum of a horse which had received chronic treatment with thyrotropic extract was capable of reducing the bas...

THE QUANTITATIVE DETERMINATION OF THE GONADOTROPIC MATERIAL OF URINE OF WOMEN AFTER CASTRATION AND THE MENOPAUSE AND OF NORMAL MEN

During the past few years we have been intermittently engaged in the development of methods for the quantitative estimation of small amounts of gonadotropic substances. We have reported that small quantities of the gonadotropic substances of urine of pregnant women and of unfractionated anterior lobe extracts which were added to boiled urine of normal men were satisfactorily recovered by adsorption on benzoic acid or preciptation with tungstic acid 1, 2). In that work the assay was based on the induction of vaginal opening and cornification in immature rats. Since the active material from these sources was successfully recovered by these methods, we assumed that the gonadstimulating substances of various urines could likewise be determined. However, other investigators who were using the alcohol precipitation method and a different method of assay found that the benzoic acid method gave low results when applied to urine obtained from women after castration or the menopause (H. M. Evans, O. W. Smith, L. Le...

XI.—The Relation of the Pituitary Gland to Muscle Creatine

Braier (1931) showed that hypophysectomised dogs on a complete diet excrete 24 per cent. less urinary creatinine than the controls, and 35 to 40 per cent. less when fasting. Schrire and Zwarenstein (1933, 1934) found that injection of anterior lobe extracts increased the urinary creatinine in rabbits.These results afford evidence of an endocrine relationship between the anterior lobe of the pituitary and urinary creatinine. In view of the well-established relationship between urinary creatinine and muscle creatine the present authors decided to investigate the relationship of the anterior lobe to muscle creatine. An effect on phosphocreatine of muscle was reported by Marenzi (1933), who obtained a decrease of 33 per cent, following removal of the anterior lobe of the pituitary. The effect of hypophysectomy and of injections of anterior lobe extracts on muscle creatine has not been previously investigated.

THE EFFECT OF HYPOPHYSECTOMY AND OF PHYONE INJECTIONS ON THE PANCREAS AND LIVER OF THE NEWT

Observations on the histology of the pancreatic islands of animals in hyperpituitary or hypopituitary states are rare in contrast to the abundance of physiological data. Anselmino and his co-workers (1, 2, 3) have described an increase in number and size and a new formation of islands in rats after 6 to 7 injections of an anterior lobe extract. Aron (4) has induced a premature appearance of islands in foetal guinea pigs injected in utero with an anterior lobe preparation. Kojima (5) discovered an accumulation of granules in the island cells of rats after posterior lobe feeding but none after anterior lobe feeding. Reports of negative or doubtful findings predominate, such as those of Putnam et al (6) and Evans et al (7) who found pancreases much larger than normal but no increase or histological differences in islet tissue of dogs made acromegalic by long-continued injections of anterior lobe extracts. Lucke (8) also observed no histological changes in islands of rats whose carbohydrate metabolism had bee...

Hypophysectomy of birds V-Effect of replacement therapy on the gonads, accessory organs and secondary sexual characters of hypophysectomized fowls

In the course of making the necessary replacement therapy to carry the birds over the early post-hypophysectomy period, certain effects of anterior lobe extracts on the newly hypophysectomized fowl were observed. These observations were re-enforced by a long duration experiment with anterior lobe extracts, and by other experiments designed to show the effect of sex hormones and also of thyroxine on hypophysectomized fowls. The account given below concludes the description of our work on hypophysectomized fowls.

THE HYPOPHYSEAL GONADOTROPIC HORMONES

The discovery in 1926-1927 that the anterior pituitary gland secreted a substance essential to the functioning of the gonads has been followed by many investigations, which have greatly extended the knowledge of the pituitary-gonad interrelationship. I do not wish to give the impression that important work in this field had not been done prior to 1926-1927. The observations published here and abroad at that time were only a final demonstration of the important role played by the anterior hypophysis in reproduction. More than twenty years ago dishing and his co-workers1and Aschner2had demonstrated that hypophysectomy caused an atrophy of the reproductive system. By partial gonadectomies, parabioses and the like it had also been shown that some extragonadal factor was essential to gonadal function. Evans and Long3had secured excessive luteinization of the ovaries in normal rats by the injection of anterior lobe extracts.

The Use of Gonadotropic Hormones in the Treatment of Undescended Testes: Preliminary Report

Smith and Engle have shown that the injection of extracts of the anterior lobe of the pituitary into immature animals produces an increased growth of all the tissues of the testes, and, as a result of stimulation of the interstitial tissue, enlargement of the penis and accessory genital glands. Spermatogenesis is not produced in immature mammals by means of these extracts. Similar results are obtained with extracts of pregnancy urine, the gonadotropic principle (A.P.L. or anterior-pituitary-like hormone) of which is probably derived from the placenta. Engle has also shown that the injection of extracts of anterior lobe or of pregnancy urine causes descent of the testes in immature monkeys, in which animals they are situated in the inguinal canal.Eleven patients with undescended testes, aged 4(1/2) to 15 years, have been treated with the gonadotropic hormones extracted from pregnancy urine. The dose used in most cases was 500 rat units injected intramuscularly twice weekly. Five of the patients had bilaterally undescended testes: during treatment both testes descended into the scrotum in two cases, one descended in each of two cases, and in the remaining case the position of the testes is unchanged. The remaining six had unilaterally undescended testes; of these, three have descended into the scrotum. Thus, nine of sixteen undescended testes have entered the scrotum during treatment. The time taken to effect this change varied from two to eleven weeks. The testes which have not yet responded have received treatment for from three to nine weeks. The mechanism whereby the descent is brought about is unknown.In view of the rather unsatisfactory surgical results, it is felt that in the treatment of undescended testes a trial should be made of this form of therapy before surgical measures are considered.

Societies and Academies

LONDON Royal Society, January 31. R. T. HILL and A. S. PARKES: Hypophysectomy of birds. (6) Plumage changes in hypophysectomised fowls. Hypophysectomy of the Brown Leghorn cock results in the loss of most or all of the black pigment from the feathers of the under-neck, breast and legs. The later growing feathers, particularly, are usually devoid of black and may be extensively fringed. The new plumage over the rest of the body is characterised by loss of black pigment and increase of fringing due to lack of barbules. These changes are so similar to those which follow thyroidectomy that they may reasonably be supposed to be due to thyroid deficiency, which is well known to follow hypophy-sectomy in mammals. (5) Effect of replacement therapy on the gonads, accessory organs and secondary sexual characters of hypophysectomised fowls. Fowls injected with ox anterior lobe extract for 4–6 days after hypophysectomy all showed a temporary increase in the size of the comb and, in the male, the atrophy of the testes was slightly retarded. Prolonged injection after operation, however, failed to avert (a) the comb shrinkage, (b) the testes atrophy, or (c) the plumage changes, which follow hypophysectomy. Attempts to restore the atrophied gonads and combs of hypophysectomised birds by injections of anterior lobe and urine of pregnancy extracts were comparatively unsuccessful. H. MUIR EVANS: The brain of Gadus with special reference to the medulla oblongata and its variations according to the feeding habits of different Gadidae (1 and 2). The divergence of opinion of the significance of the various lobes in Gadus has necessitated a detailed microscopic examination of serial sections of the medulla of the whiting; the result of which is to confirm the views of Goronowitsch and others, and to dispute the conclusions of C. J. Herrick. The facial lobes described by the former writers are held to be true facial lobes, comparable to the single facial lobe of the roach, as a type of cyprinoid brain, which is the result of the fusion of two facial elements. Different species of gadoids can be classified according to their diet, and both diet and dentition are reflected in the pattern of the medulla oblongata. At one extreme is the haddock, feeding on Crustacea and mollusca, with a large facial lobe and a small somatic sensory lobe, and at the other end species like the ling and the pollack, feeding almost entirely on fish, with a small facial lobe and a very large somatic sensory lobe. In between there is a gradual transition both in types of medulla and in feeding habits, as we pass from the haddock to the cod, whiting, ling, pollack and hake. H. W. FLOREY and H. E. HARDING: A humoral control of the secretion of Brunner's glands. The secretion of Brunner's glands of the cat occurs independently of extrinsic innervation. The glands are activated after the taking of food by a blood-borne stimulus—a hormone or secretagogue.

Induction of fertility and pregnancy in the anœstrous ferret

Bissonnett (1932) was able to induce complete œstrus in three female ferrets by evening illumination from October 12 onwards, but similar treatment of a male from October 12 to December 22 failed to carry spermatogenesis beyond the spermatocyte stage. Mating, therefore, resulted only in pseudopreganancy. In a second series of animals illuminated from December 7 onwards, spermatorgenesis was secured during February and a litter was born on April 11 (Bissonnette, 1933). The normal untreated male, however, usually becomes fertile during February (Allanson, 1932) and the first litters of the season may be born early in April, so that Bissonnette cannot be said to have induced fertility outside the limits of the normal breeding season. Bissonnette’s failure to bring about premature spermatogenesis, though involving one animal only, suggested that the male was much more refractory than the female, especially since anterior lobe extracts and urine of pregnancy extracts readily cause ovulation in the anœstrous ovary (Hill and Parkes, 1930), while such extracts cause little reaction in the quiescent winter testis. It seemed, however, that a combination of additional light and gonad-stimulating extracts might be effective, and the present paper records experiments carried out on these lines, as a result of which pregnancy was induced in light-treated females well outside the limits of the normal breeding season.

Effect of Injections of Pituitary Whole Gland Extract on Immature Alligator

The efficacy of the anterior hypophysis in producing precocious development of the reproductive system in lower vertebrates has been shown by the recent studies of Burns and Buyse,,, and Burns, who used as subjects larvae and recently metamorphosed salamanders. Reptiles have rarely figured in pituitary investigations. Herlant found that injections of anterior lobe extract caused a general hypertrophy of the reproductive system of Lacerta, Noble and Bradley state that hypophysectomy delays moulting in Hemidactylus, Schaefer reports testicular atresia in Thamnophilis following hypophysectomy, with a partial restoration of the testes to the normal condition following several hypophyseal implants, and Houssay produced ovulation in a single female snake, Xenodon, after similar implantations. All of these experiments were carried out with mature animals. In the present work, the immature alligator, Alligator mississipfiensis, was chosen for study. The average total length of the first group of animals used was 24 cm., and their approximate age at the beginning of the experiment was 4 months. Intraperitoneal injections into 10 animals of 0.5 cc. per animal of the Parke, Davis & Co. sheep whole gland alkaline aqueous extract were made 3 times a week, a similar group of 10 animals serving as controls. Gross examination after 6 weeks of injections, showed a great hypertrophy of the testes of the single male member of the experimental group. A slightly less, but still striking, hypertrophy of the gonads of the injected females was observed, together with lengthening and increased convolution of the oviducts. Due to lack of external evidences of sex in the immature animals, the ratio of males to females in this series was purely fortuitous, but a second series (see below) showed a preponderance of male animals, thus approximately equalizing the total number of males and females in the two series.

The effect of anterior lobe extract or concentrated human urine of pregnancy upon the early part of gestation in the rabbit

The effect of anterior lobe extract or concentrated human urine of pregnancy upon the early part of gestation in the rabbit

A Rapid Test for Pregnancy on Xenopus lævis

IN a recent communication Bellerby (1933)1 has shown that injection of acid or alkaline extracts of bovine anterior lobe of the pituitary gland into female South African clawed toads (Xenopus Iœvis) produces extrusion of ova through the cloaca within 18 hours.