Effect of Various Sterols on Thymus in the Adrenalectomized Rat

Abstract

It has been pointed out that when an organism is seriously injured by an acute, non-specific, nocuous agent, a characteristic syndrome occurs, which consists of a rapid involution of the thymus and lymphatic system, oedema formation, with fluid in the pleura! and abdominal cavities, loss of muscle tone, fall in body temperature, lung hemorrhages, and ulcers in the digestive tract. This syndrome has been given the name “Alarm Reaction”. 1

It has been shown further, 2 that, while adrenalectomy facilitates the production of all other symptoms of this “Alarm Reaction”, it prevents the thymus involution. Physiological NaCl solution given to the animals restores their resistance to damaging influences, but does not enable the thymus to involute. Adrenaline is without effect both on the resistance of rats and on the ability of the thymus gland to respond to toxic stimuli. In animals maintained with very large doses of cortin slight involution will occur. This may be due to small amounts of some contaminating substance present in the cortin, or to the cortin itself. The only other substance which was found to be active in causing thymus involution following bilateral adrenalectomy was oestrone. 3

The following investigations were carried out in order to determine whether the thymus of adrenalectomized rats would involute following the administration of sterol substances other than oestrone and at the same time to study the toxicity of these substances in such animals.

Rats varying in age from 40 to 162 days were used, 5 to 8 rats in each series with an equal number of controls. They were given standard Purina food and normal saline. Adrenalectomy was performed in one stage under ether anesthesia. Following a 24-hour rest period injections were begun.

The substances investigated were: 1. oestrone; 2. oestradiol; 3. pregnandiol; 4. dehydroandrosterone acetate; 5. cholestenone; 6. cholestenone acetate; 7. cholesterol; 8. progesterone; 9. androstene-diol; 10. testosterone; and 11. testosterone propionate.∗ These compounds were administered in oil solution by daily subcutaneous injections. All the animals were autopsied for evidences of the alarm reaction, and the weights of the thymus, spleen and lymph nodes recorded. Survival was used as the criterion of toxicity.

Eight male rats were given 100 gamma of oestrone daily for 10 days. By that time half of the animals died. The remainder and the control animals were killed and autopsied. The oestrone produced a decided decrease in the size of the thymus, spleen and lymph glands.

Thymus Weights. Rats given oestrone: 256, 151, 293, 153, 185, 350, 237, 143; average 221. Controls: 580, 512, 514, 366, 460, 378, 495; average 472.

A group of seven 80-day-old females resisted the same dose of oestrone for 14 days. The thymus was even more markedly involuted, the average weight being 81 mg., the control rats averaging 322 mg.

Pregnandiol in daily doses of 100 gamma for 12 days had no toxic action and did not alter the thymus gland of 7 male rats. Daily doses of one mg. of pregnandiol for 17 days were also without effect in a series of 8 females.