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Testosterone undecanoate (TU), either dissolved in arachis oil or as micro-crystal suspension, displays androgenic activity on oral administration to rats in the Hershberger test. The solution in arachis oil is more active than the crystal suspension. When [3H]TU is administered orally to rats, most of it is metabolized in the intestinal wall. The majority of the metabolites probably lose their undecanoate group and are absorbed via the portal vein. The non-metabolized [3H]TU and at least two metabolites are absorbed exclusively via the lymphatic system. One of these metabolites has been identified as 5α-dihydrotestosterone undecanoate (5α-DHTU). TU has no harmful effects on the liver of the rabbits on oral administration.

Thirty-six steroids have been examined for their ability to protect the rat against the catabolism, soft-tissue calcification and skeletal lesions normally produced by chronic dihydrotachysterol (DHT) intoxication. Among these compounds, norbolethone, SC-7294, and fluoxymesterone proved to be most efficacious in all these respects. Their anticatabolic action was almost equalled by several other anabolic steroids, but with regard to the prevention of soft-tissue calcification and skeletal lesions they were by far the most potent of the steroids tested. The anabolic effect of the compounds examined was comparatively independent, not only of their androgenic potency, but also of their renotrophic action and their ability to prevent the DHT-induced soft-tissue calcification and skeletal lesions.

Anti-anabolic action of a lathyrus factor (BAPN) and of cortisone and anabolic action of androgenic steroids Dianabol (17α-methyl-17β-hydroxy-androsta-1,4-dien-3-one) and Ora-Testryl (9α-fluoro-11β-hydroxy-17α-methyltestosterone) on the healing of fractured humeri in rats was investigated. Tensile strength of healing callus measured at 1st, 2nd and 3rd week after fracture was determined to assess the difference in action between the compounds studied. Healing bones were also studied histologically. Significant decrease of tensile strength of callus was observed in BAPN treated rats at 2nd and 3rd week after fracture. Less marked decrease was noted in cortisone treated animals. Certain delay of new bone formation was notable, histologically, in callus of animals treated with anti-anabolic compounds. Both androgens studied were found to increase significantly tensile strength of callus at 1st and 2nd week after fracture. Increase of tensile strength was associated with marked stimulation of new bone formation and calcification of callus, observed on histological preparations.

The present work is concerned with early effects of a single injection of 1.5 mg testosterone propionate into 5 day old female rats (injected rats). Effects of »anabolic steroids« given to rats shortly after birth, generally on the 5th day, were also studied. Untreated littermates served as controls. As early as 5 days after injection (rat's age 10 days) a reduction in ovarian weight was noticeable. At 10 days after injection the ovaries weighed less than those of controls. Vaginal smears showing cornified cells were obtained from injected rats about 5 days prior to controls. At the controls' first oestrous the ovaries of the injected rats weighed approximately 60 per cent of those of the controls. At this time the ovaries of the controls contained large follicles but no corpora lutea. Confirming previous results of other workers, injected rats observed for about 2 months presented constant vaginal oestrous and ovaries without corpora lutea. The ovaries weighed less than half those of the controls. This result was obtained irrespective of whether one ovary had been removed a fortnight previously, or not. Rats given 1.5 mg testosterone propionate at 20 days of age did not show any persistent effects. Records of weight of body, pituitary gland and adrenals were also in agreement with results of other investigators. Results obtained from similar experiments with »anabolic steroids« (19-nor-testosterone, 1-methyl-androst-1-enolone-oenanthate and methan-drostenolone = Durabol, Primobolan and Dianabol, respectively) indicated that, in the doses studied so far, a depression of endocrine activities and/or persistent defects in the development of female accessory reproductive organs and ovarian function may occur in rats after an injection given within 24 hours after birth or at 5 days of age. The importance of further investigations with regard to the clinical use of »anabolic steroids«, particularly in newborn infants, is discussed.

The anabolic and androgenic properties of ethylestrenol, norethandrolone and methyltestosterone were compared by means of a quantitative levator ani assay (Hershberger 1953). In a second assay of this kind ethylestrenol and methandrostenolone were compared. In both instances ethylestrenol was shown to be a potent anabolic substance with by far the highest anabolic/androgenic ratio.

Experiments with adult rats treated with dexamethasone showed a decreased retention of radioactive calcium and strontium as compared with the control animals. In addition a marked reduction in weight was observed probably due to dehydration. In animals which had additional injections of nortestosterone compounds, i. e. Durabolin® and Anadur® respectively, these effects of cortisone were not counteracted although animals treated with nortestosterone compounds alone showed an increased retention of radioactive calcium as compared with the control animals.

The effect of toxic lathyrus factor beta-aminopropionitrile (BAPN) and of anabolic steroid 17-ethyl-19-nortesterone (»Nilevar«) on the 35S uptake by the healing fractures of rats' humeri was studied. The radioactivity of callus (C) in fractured humerus and in shaft of intact (I) humerus was recorded, one, two and three weeks after fracture, and C/I ratio calculated. BAPN diet resulted in the decrease of C/I ratio as compared with normal control. In rats treated with »Nilevar« C/I ratio was higher than that in both normal control and BAPN fed animals. It is apparent that BAPN inhibits and »Nilevar« promotes those processes of healing of bone which are associated with changes in connective tissue mucopolysaccharides and which may be studied by 35S uptake method.

The long-term effect of two androgenic (testosterone propionate, testosterone phenylpropionate) and four anabolic hormones (3β,17α-dihydroxy-17α-methyl-androst-5-en, 17β-hydroxy-17α-methyl-androsta-1,4-dien-3-one, 17β-hydroxy-19-norandrost-4-en-3-one-17 phenylpropionate, 17β-hydroxy-19-norandrost-4-en-3-one-17 decanoate) on the circulating eosinophils was investigated in normal and adrenalectomized female adult Long-Evans rats. All the hormones studied caused a significant increase in the number of the circulating eosinophil cells. The highest counts were most rapidly found in groups which received 3β-17α-dihydroxy-17α-methylandrost-5-en in aqueous suspension. With other hormones given in an oily solution the eosinophils reached the highest counts later; this did not occur with 17β-hydroxy-19-norandrost-4-en-3-one-17 decanoate until 72 hours after its administration. In adrenalectomized groups higher eosinophil counts were found than in non-operated groups after androgenic or anabolic treatment. The differences were most significant when the highest counts of eosinophils were present. It is suggested that these androgenic and anabolic hormones stimulate the production of eosinophils. In non-operated groups this eosinophilia is partially counteracted by the endogenous corticosteroids which cause the eosinophils to migrate from the blood to the tissues.

Androisoxazole, 17α-methylandrost-4-en-17β-ol[2,3-d]isoxazole, 17α-ethyl-19-nor-estra-4-en-17β-ol and testosterone were evaluated experimentally for anabolic activity by means of nitrogen balance studies and for androgenic activity on the basis of increase weight of the ventral prostate gland in a 10-day assay. Under these conditions their anabolic:androgenic activities relative to methyltestosterone (= 1.0) and ratios were: androisoxazole (1.55/0.22) 7.0, methylandrostenol-isoxazole (1.2/0.15) 8.0, ethylestrenol (1.7/0.21) 8.1 and, of historical interest, testosterone (0.38/0.57) 0.67. The first three agents thus are intermediate in degree of dissociation of anabolic and androgenic properties between methyltestosterone and the more promising isoxazole-conjugated and pyrazole-conjugated (stanozolol) agents discussed previously.

Although the rat's 'levator ani' muscle has been widely used for screening and evaluating nonandrogenic anabolic steroids, there has been some confusion about the nature of the muscle itself. To clarify this situation, the anatomical literature was searched and numerous dissections were performed. It was found that the name 'levator ani' is incorrect and misleading. This muscle is not homologous to the one called levator ani in man, cat, and dog, but is actually the dorsal bulbocavernous, a muscle peculiar to rodents. It attaches to the bulb of the urethra; it is absent in the female rat; and, unlike the true levator ani, it is clearly part of the male reproductive system. To determine whether the masculinizing action of anabolic steroids is confined to this particular organ, its response to three such steroids was compared with the responses of several other genital organs. Although these steroids had little effect on the accessory sex glands, their strong action on the dorsal bulbocavernous was accompanied by similarly accelerated growth of all other muscular and erectile parts of the male genital system, including the penis. These results cannot be understood in terms of the traditional dichotomy of androgens and nonandrogens. A third category of quasi-androgens is needed, to accommodate synthetic steroids with some, but not all, of the masculinizing actions of testosterone.