Effect of Adrenotropic Hormone on the Natural Resistance of Hypophysectomized Rats

Abstract

In the present communication the protective effect of the adrenotropic fraction of anterior hypophysis on the natural resistance of hypophysectomized rats to histamine poisoning is reported.

We were unable to obtain the adrenotropic fraction prepared according to Collip's method 1 and as a source of this material we used an acid extract of the anterior hypophysis boiled for 20 minutes. Such a heated acid extract still contains adrenotropic activity, but the thyrotropic hormone and gonadotropic and growth factors are destroyed (Spence 2 ). Preliminary experiments showed that such heated extracts still possess varying degrees of adrenotropic effect in hypophysectomized rats.

The acid extract of dried anterior hypophysis was prepared by the method of Loeb. 3 Ten grams of the powder was extracted with 100 cc. of 1/2% acetic acid overnight. The fluid was brought to pH 6.6, centrifuged and then brought to pH 7.8 and filtered through a Seitz filter. The heated fraction was prepared by suspending the extract in boiling water for 20 minutes.

Seventy-seven rats of Wistar stock, free from Bartonella muris, were used in these experiments. Of these, 14 were normal unoperated controls; 19 were completely hypophysectomized but untreated; 23 were hypophysectomized and injected with 1 cc. of acid extract of anterior hypophysis daily from the day of operation to the day of the test; 21 were hypophysectomized and injected daily with 1 cc. of the heated acid extract of anterior hypophysis.

Ten days after the operation the rats were injected intraperitoneally with amounts of histamine varying from 300 to 1600 mg. per kg. of body weight as indicated in Table I.

The minimal lethal dose of histamine in the control rats of Wistar stock∗ was about 1400 mg. per kg. The hypophysectomized rats untreated were killed in all instances by amounts of histamine greater than 400 mg. per kg. and only half the number of rats survived this dose. Hypophysectomized rats repeatedly injected with an acid extract of desiccated anterior hypophysis from the day of operation survived in some instances 900 mg. of histamine per kg. When treated with the adrenotropic fraction (the heated acid extract) hypophysectomized rats survived as great an amount as 700 mg. per kg. All succumbed to amounts in excess of 700 mg. per kg. of body weight.