Anterior pituitary extract

Schedule D contains drugs of biological (animal or human) origin. Products covered by this division are vaccines, bacteriophages, toxins and toxoids, antitoxins, antisera, human plasma components, insulin, anterior pituitary extracts and anticoagulants. 

C39. Cuthbertson, D. P., Shaw, G. B., and Young, F. G., The anterior pituitary gland and protein metabolism. 3. The influence of anterior pituitary extract on the rate of wound healing. J. Endocrinol. 2, 475-478 (1940-1941). 

The injection of moderate amounts of an anterior pituitary extract modifies the thyroid in such a way that it produces more thyroid hormones. Soon after injection, the gland grows, the cells enlarge and proliferate, iodine uptake is accelerated, and thyroglobulin synthesis and thyroxine release through proteolysis are increased. It now seems likely that all these effects result from the action of several hormones, some of which are still not known. 

The hexokinase theory originated from experiments by Colowick, Cori, and Slein [128]. The combined effects of three hormones—an anterior pituitary extract, an adrenocortical extract, and insulin— were studied on crude or purified hexokinase preparations obtained from kidney, brain, liver, and heart of normal and alloxan-diabetic rats. We shall first present the results obtained on normal rats, and then those obtained on diabetic rats. 

In the normal rat, a labile anterior pituitary extract inhibited crude hexokinase in brain, liver, kidney, and heart. The inhibition was counteracted by insulin. When, in addition to the anterior pituitary extract, an adrenocorical extract was put in the presence of crude muscle hexokinase preparations, the inhibitory effect was greater than that seen with the anterior pituitary extract alone. The adrenocortical extract alone had no effect on hexokinase prepared from normal muscles. 

In alloxan-diabetic animals, the following observations were made. The hexokinase activity of several tissue extracts was very low hexokinase activity was not directly stimulated by insulin hexokinase activity was inhibited by an anterior pituitary extract, except in brain preparation the inhibitory effect of the anterior pituitary extract was counteracted by insulin contrary to what was observed when muscles obtained from normal animals were used, the adrenocortical extract inhibited alloxan-diabetic muscle hexokinase in the absence of the anterior pituitary extract and the effect of the adrenocortical extract could be relieved by insulin. 

Because of the significance of such results, several laboratories tried to repeat this work, and, although it could be demonstrated that an anterior pituitary extract inhibits hexokinase, it soon became clear that this effect on hexokinase and the diabetogenic effect of the pituitary hormone are unrelated. 

Colowick, S.P., Cori, C.F., Slein, M.W. The effect of adrenal cortex and anterior pituitary extracts and insulin on the hexokinase reaction. J. biol. Chem. 168, 583-596 (1947)... 

Metabolic Principle (O Donovan and Collip, 1938).—Even in thyroideotomised animals injection of anterior pituitary extracts may stimulate metabolism, as shown by increased oxygen con-... 

If anterior pituitary extract is administered by the oral route gonadotropic effects are not observed unless 15-30 times the effective intraperitoneal dosage is given in rabbits (Lupine, 1931). Janssen and Loeser (1930) found 30-40 times the intraperitoneal dosage ineffective Avhen given orally to rabbits. In 1931, however, they reported gonadotropic reaction... 

Hormones have a profound effect on carbohydrate metabolism. Great interest has been aroused by reports of hormonal control of hexokinase activity by specific proteins in animal tissues.99- 100 Hexokinase action is the rate-limiting step in the uptake of D-glucose by muscle. Hexokinase is inhibited in diabetic muscle, but the inhibition can be partially reversed by insulin. A protein fraction from the anterior pituitary gland will inhibit the hexokinase of extracts of brain and muscle, and the effect of this... 

Specific dissection is performed on the brain and pituitary gland. Hypothalamic fragments may be dissected and shock frozen immediately in liquid nitrogen, for later extraction and determination of hypothalamic peptides. The pituitary gland is dissected, the posterior pituitary is stored separately, and the anterior pituitary is halved by a median-sagittal cut to obtain separate tissue samples for histology (fixation), and for subsequent analysis of hormone contents (stored frozen at -20 °C until hormone assay). 

Extract of CA from D. punctata contains at least four allatostatins. These have the same retention times on HPLC as the allatostatins isolated from the brain and have similar abilities to inhibit the synthesis of JH by CA in vitro. Thus it may be concluded that the members of this family of related allatostatins produced by neurosecretory cells of the brain are transported to the CA where they act to depress the rate of JH synthesis. This neural method of delivery of peptidergic neurosecretion from brain to target organ is analogous to that of vertebrates in which h3rpothalamic factors are released into a portal system and delivered to the anterior pituitary, as Scharrer noted (4). 

In the 1950s, Guillemin and Rosenberg, and Saf an and Schally discovered that hypothalamic extracts that could stimulate the release of ACTH from anterior pituitary cells. This represented another connection between the brain and the endocrine system. CRF is the major regulator of the baseline and stress-induced release of ACTH, P-endorphin, and other proopiomelanocortin-derived peptides from the anterior pituitary. 

Extracts of the intermediate-posterior lobe of the mouse pituitary contain approximately a tenth as much ACTH activity as extracts the anterior lobe (Mains and Eipper 1975). In extracts of both the anterior and the intermediate-posterior lobes, about half of the immunological ACTH activity is similar in size to porcine ACTH (Mr = 4000-5500). Two higher M, forms of ACTH account for the remainder of the ACTH activity. About 40 % of the immunological ACTH activity in anterior lobe extracts has a Mr of 6500-9000. Extracts of both the anterior lobe and the intermediate-posterior lobe contain ACTH activity with a Mr of 20,00-30,000. 

In these experiments, the extract was injected intravenously into the test rats which were bled 10 min later from the jugular vein. The effect of the extract on plasma LH activity of the test animals was estimated by the ovarian ascorbic acid depletion test. The factor has been found to be effective in a variety of situations. It is active in normal female rats and in ovariectomized rats in which the release of LH has been inhibited either by administration of gonadal steroids or by lesions in the median eminence (ME) (2). This latter observation is important because it indicates that the LRF acts directly on the anterior pituitary to release LH. An indirect action via the nervous system would have been blocked by these lesions which interrupted neural control over LH secretion. Further evidence that the LRF acts directly on the gland to release LH has been provided by the experiments of Campbell t l. (7) in rabbits and Nikitovitch-Winer (8) in rats. They showed that infusion of hypothalamic extract directly into the anterior lobe of the pituitary could evoke ovulation. Systemic administration of the same dose of extract was without effect. Schally Bowers (9) have demonstrated an LH-releasing action of h3rpothalamic extracts on pituitaries incubated vitro and we have recently confirmed this observation (Watanabe Ratner, unpublished data, 1965). This provides further evidence that LRF acts directly on the h3rpophysis. 

Luteinising Hormone (LH), prolan B, or factor B, brings about formation of the corpus luteum. FSH and LH are hormone proteins, FSH occurs chiefly in acid extracts of the anterior pituitary, and LH in alkaline extracts. 

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