JOURNAL TRANSCRIPT
Brit. J. Pharmacol. (1953), 8, 242.
THE EFFECT OF DESOXYCORTICOSTERONE ACETATE ON THE RELEASE OF ADRENOCORTICOTROPHIN BY THE PITUITARY GLAND BY
J. R. HODGES From the Department of Pharmacology, School of Pharmacy, University of London (RECEIVED DECEMBER 3, 1952)
DOCA.-Deoxycortone acetate, B.P. (Organon), The results of experiments performed in many laboratories indicate that the adrenocorticotrophic was used. Stock solutions were prepared containing activity of the pituitary gland is controlled, to some 5, 10, 15, and 20 mg. DOCA per ml. in arachis oil. extent, by the level of adrenocortical hormones in The DOCA tended to crystallize out from the solutions of highest concentration, when the solutions were the blood. Many workers have shown that the allowed to stand, but the steroid redissolved readily chronic administration of adrenocortical extracts on heating. The injections of DOCA were administo rats results in atrophy of the adrenal cortex. tered in volumes of 1 ml. per 100 g. body weight of Sayers and Sayers (1947) and Long (1947) demon- the animals. The solutions were warmed to 37-400 C. strated, in rats, that the fall in adrenal ascorbic acid before injection to facilitate administration and to concentration, which normally follows the appli- keep the highest concentration of DOCA in solution. cation of various types of stress stimuli, could be Removal and Analysis of Adrenal Glands prevented by previous treatment of the animals The removal of adrenal glands from dead or anaeswith adrenocortical hormones. thetized animals was carried out by the dorsal apSayers and Sayers (1947) found that several proach. Excised adrenal glands were dissected free crystalline cortical steroids, including desoxycorti- from fat and connective tissue with a fine pair of costerone, were effective in inhibiting pituitary scissors. Care was taken to remove all traces of adrenocorticotrophic activity. However, Moya extra-adrenal tissue without damaging the capsule. weighed as quickly as possible to and Selye (1948), Hall, Finerty, Hall, and Hess The glandsthewere loss of moisture, and placed in test(1951), and Gershberg, Fry, Brobeck, and Long minimize tubes containing a little acid-washed sand and 4% (1950) did not find that DOCA prevents the release trichloracetic acid solution. They were minced with of ACTH in response to stress. the aid of a glass rod and the sand, and the tubes The experiments which form the subject of this were stored in a refrigerator overnight. The ascorbic paper were carried out to re-examine the effect of acid contents of the tubes were determined on the DOCA on the stress-induced secretion of ACTH following day by the method of Roe and Kuether and to determine whether this steroid possesses any (1943). The results were expressed as mg. ascorbic pituitary inhibitory effect. Changes in the con- acid per 100 g. adrenal tissue. centration of ascorbic acid in the adrenal glands RESULTS were used as indices of increased adrenocortical, Adrenalectomy on the Unilateral of The Effect and hence of adrenocorticotrophic, activity. The Ascorbic Acid Concentration in the Intact form of stress employed was unilateral adrenalAdrenal Glands of Normal Rats ectomy under ether anaesthesia. One hundred and eight animals were used in this MATERIALS AND METHODS experiment. Control animals were killed by a The experiments were performed on male albino blow on the head and their adrenal glands were Wistar rats, weighing from 130 to 250 g. and main- removed as quickly as possible. Test animals were tained on a diet of cubes, cabbage, and water. anaesthetized with ether and their left adrenal Twenty-four hours before being used the rats were glands were removed and discarded. The skin transferred to a room in which the temperature was were closed and the animals were allowed thermostatically controlled at 70' F. and where the incisions The rats were experiments were performed. During the course of to recover from the operations. after unilateral intervals time various after killed to the experiments the animals were given access food adrenalectomy. The right adrenals were removed, and water.
DOCA AND THE RELEASE OF ACTH
243
Unilateral adrenalectomy under ether anaesthesia resulted in a very rapid depletion of the ascorbic acid concentration in the intact adrenal glands. The concentration of adrenal ascorbic acid fell quickly and reached its minimum value of approximately 58% of the normal level, one to Mean Ascorbic Time Interval in Hours Acid Concentration two hours after the performance of the operationUnilateral Between No. of Rats mg /100 g Adrenal This low adrenal ascorbic acid concentration was Adrenlectoy and Tissue ± Standard Sacrifice Error maintained for four hours. After eight hours the level of ascorbic acid had commenced to return to 438 ±5 24 Controls A 367±8 12 Controls B normal. After sixteen hours the mean concen290±15 12 1 264±12 12 tration was slightly higher than normal. 251 ±8 2 12 The time taken to anaesthetize a rat and to' 4 261±16 12 8 12 363± 18 remove one of its adrenal glands was approxi475 ±17 16 12 mately four minutes. The fall in adrenal ascorbic acid concentration was found to take place very and their ascorbic acid contents were determined. rapidly. Four minutes from the commencement of The members of one group of animals were anaes- anaesthesia there had occurred a significant thetized with ether and their right adrenal glands, (P