There are three animal preparations which may be used for the biological assay of pituitary pressor potency: the spinal cat (Dale and Laidlaw, 1912; Hogben, Schlapp, and Macdonald, 1924), the anaesthetized dog (Hamilton and Rowe, 1916;Kamm, Aldrich, Grotte, Rowe, and Bugbee, 1928), and the anaesthetized rat (Landgrebe, Macaulay, and Waring, 1946); of these, the rat preparation is the most economical, the most sensitive, and the most reliable.In a previous report (Dekanski, 1951) dealing with the preparation and qualitative assay of a pressor fraction from normal urine, N: N-dibenzyl-p-chloroethylamine (" Dibenamine ") was injected into the rat preparation in order to inhibit the action of certain pressor substances known to be present in fresh urine. Dibenamine was found to have a potent and prolonged action in abolishing the usual pressor effects of adrenaline, noradrenaline, hydroxytyramine, nicotine, and piperidine. On the other hand, the rise in blood pressure produced by pitressin or by the urinary pressor fraction was not abolished. The results of these experiments indicated that a quantitative assay of the pressor potency of pituitary extracts might be readily obtained by means of a comparatively simple rat's blood pressure preparation into which dibenamine had been injected.In the rat preparation described by Landgrebe et al. (1946) for pressor assays of pituitary extracts, the vagi and associated sympathetics are severed and the posterior cord pithed. Neither is, in fact, necessary if the rat preparation is treated with dibenamine. Subcutaneous urethane anaesthesia was found to be as efficient as that by " Dial " followed by urethane both injected intraperitoneally. The modified rat's blood pressure method, appears to be more satisfactory and more specific than any other method for the assay of pressor activity of pituitary preparations. METHODSTechnique.-A male albino rat weighing about 300 g. is anaesthetized with urethane (175 mg. per 100 g. body weight) injected subcutaneously.

1The relationship between gastric mucosal damage and synthesis of gastric glycoproteins, as measured by the rate of incorporation of N-acetyl-[3 H]glucosamine, was investigated in rats after fasting and restraint stress and a single administration of aspirin (200 mg/kg, orally), phenylbutazone (200 mg/kg, orally), prednisolone (200 mg/kg, orally), or adrenaline (2 mg/kg, i.p.). In one experiment, the effects of aspirin and phenylbutazone on carbohydrate content of the glycoproteins were also determined. 2 Restraint stress, phenylbutazone and aspirin resulted in acute gastric mucosal erosions in some of the rats. Adrenaline produced severe sub-mucosal haemorrhage, but no erosions or ulceration, while prednisolone and fasting gave no gross pathology. 3 The rate of incorporation of N-acetyl-[3 H]glucosamine into glycoproteins was decreased after all treatments except adrenaline. In the groups receiving restraint stress, aspirin or phenylbutazone, the decreases were more marked in rats which developed erosions than in those with no gastric pathology. 4 Aspirin and phenylbutazone also produced changes in the carbohydrate content of the glycoproteins, the effects again being greater in the rats which developed erosions. 5 The results are discussed in the context of a possible association between erosion formation and glycoprotein synthesis and it is proposed that inhibition of mucus glycoprotein biosynthesis may be one mode of action of stress and drugs in causing gastric mucosal damage.

An attempt has been made to modify the Sayers method for the assay of corticotrophin by substituting for hypophysectomy an injection of sufficient hydrocortisone acetate to suppress the release of endogenous pituitary corticotrophin in intact rats over the period of the assay. The results of forty such assays of subcutaneous corticotrophin seem to indicate that this procedure is about 1+ to 2 times as efficient as the original method using hypophysectomized rats. For a 2 + 2 point assay it was necessary to use a minimum of twenty-four to thirty-two rats.For some years attempts have been made to modify the technique involving adrenal ascorbic acid depletion for the assay of corticotrophin (ACTH) (Sayers, Sayers and Woodbury, 1948) by substituting hypophysectomized rats with animals in which the release of endogenous corticotrophin is sufficiently blocked by the administration of corticosteroids prior to the assay.The investigations of Ingle and Kendall (1937), Ingle, Higgins andKendall (1938), Sayers and Sayers (1947), and Gray and Munson (1951) showed that several corticosteroids inhibit the release of pituitary corticotrophin as judged by changes in ascorbic acid content and weight of the adrenal glands. At the time there was some confusion concerning the relative inhibitory effects of cortisone and deoxycortone. Sayers and Sayers (1947) were the first to suggest that several crystalline cortical steroids, including cortisone, hydrocortisone and deoxycortone, were most effective in blocking release of corticotrophin from the pituitary. Casentini, De Poli, Hukovic and Martini (1957), in a comparative test of the relative potencies of various corticosteroid preparations, found that deoxycortone had about the same activity as hydrocortisone acetate in a test on unilaterally adrenalectomized rats (Abelson and Baron, 1952;Porter and Jones, 1956).On the other hand, Fortier, Yrarrazaval and Selye (1951) showed that both cortisone and cortisone acetate were completely ineffective in preventing the release of pituitary corticotrophin in response to stress, and Moya and Selye (1948), Gershberg, Fry, Brobeck and Long (1950) and Hall, Finerty, Hall and Hess (1951) were unable to confirm that deoxycortone acetate had an D inhibitory effect under similar conditions. Hodges (1953, 1954) found that rats were far more suitable for a quantitative assay after treatment with deoxycortone acetate than after cortisone acetate, but even larger doses of deoxycortone failed to give a satisfactory preparation. Recently Hodges and Vernikos (1958) found that prednisolone and hydrocortisone were far more effective in inhibiting corticotrophin release and suggested the use of these preparations instead of deoxycortone acetate (Hodges, 1955) for a modified ascorbic acid depletion technique not involving hypophysectomy.For over two years intact rats pretreated with hydrocortisone acetate have been used in this laboratory for subcutaneous and intravenous Sayers (Munson modification) assays of various corticotrophin preparations with sati...

1Endocrine and anti-fertility studies were carried out on a fluorinated bibenzyl, bifluranol, in rats and mice. 2 A potent anti-prostatic activity of bifluranol was shown to be comparable to diethylstilboestrol (DES). In contrast, its oestrogenic potency by the oral route was about eight times less than that of DES. 3 In comparative short and long-term anti-androgenic and fertility studies in rats and in studies on sexual potency and reproductive performance in male mice, bifluranol given orally was shown to produce fully reversible suppression of accessory sexual structures without impairment of spermatogenesis and fertility. In contrast, DES administered in the same dose reduced spermatogenesis as well as accessory sexual glands. 4 Bifluranol lowered serum luteinising hormone (LH) levels without affecting follicle stimulating hormone (FSH). Under similar conditions DES reduces both LH and FSH levels. Since bifluranol does not antagonize androgen-induced stimulation of the prostate in castrated rats, its anti-prostatic effect is interpreted as a negative, hormonostatic feedback activity, mediated through a selective inhibition of LH secretion.