In preliminary experiments, mice, rats and rabbits showed considerable reduction of spontaneous movements after treatment with crude pineal extract. Whether these effects were due to toxic effects of these preparations or to a physiological action of the pineal gland could not be established.As soon as purified pineal extracts were at our disposal the problem was investigated systematically and it was found that the activity of rats treated with these extracts was considerably decreased. Moreover, pinealectomized rats were found to be more active than their non-operated litter-mates. METHODSSprague\p=m-\Dawley rats of both sexes were used. Running activity was measured in vertically revolving activity drums.Since the effects of pinealectomy on adult rats may be open to debate because of a certain amount of brain damage (or at least impairment of brain circulation) which almost always occurs during the operation, we have restricted ourselves to studying the sequels of pinealectomy in animals operated 2\p=n-\4 days after birth, which were investigated 12 weeks after pinealectomy. The operation was performed as follows: a midline longitudinal incision 6-8 mm. long is made through the skin over the junction of the parietal and occipital bones, and muscles and fascia removed with a piece of gauze. An incision, 2-3 mm. in length, is then made transversely through the carti¬ lage and dura, caudal to the junction of the transverse blood vessels. The cerebrospinal fluid is allowed to drain away for 10 sec. The pineal gland is then removed with fine forceps. There is minimal bleeding which is stopped by mild pressure with a piece of gauze, and a drop of penicillin suspension (Crystacillin 300 AS) is placed on the incision. One stitch with thin catgut is sufficient for closure of the skin wound.The animals were autopsied after completion of the experiments. The relevant

The action of pineal extracts on the genital system of several species of laboratory animals has been investigated. Determination of the phosphorus turnover in the genital organs of treated animals proved to be a significant guide to the action of pineal preparations. Doses of pineal extracts lower than those required for weight changes sufficed to produce changes in phosphorus metabolism.Apparently contradictory results encountered originally were explained when findings were evaluated on the basis of the age of the test animal and the type of extract used. Thus, in immature and/or hypophysectomized animals, crude aqueous extracts stimulate the genital system, whereas in mature intact animals the same extract often has an inhibitory effect on the same organs. The inhibitory effect could be measured also in immature mice treated with gonadotrophic hormone and this proved useful in short-term experiments.Crude glandular suspensions apparently contain both inhibitory and stimulatory principles. Partial separation of these was achieved through the use of trichloracetic acid, the supernatant fluid having predominantly inhibitory action while the stimulatory substance was found mainly in the precipitate.

The action of human chorionic gonadotrophin on mice was inhibited by small amounts of serum (1\m=.\8c.c.) and cerebro-spinal fluid (0\m=.\6ml.) from thirty-one out of forty-two mentally and physically retarded male patients aged 8\p=n-\16 yr. Serum from some of these patients also inhibited the action of thyrotrophic hormone in mice and of corticotrophin in rats. Small (1\m=.\8ml.) amounts of serum of three out of fifteen mentally normal subjects of the same age range inhibited the action of human chorionic gonadotrophin (HCG).The serum of four healthy adult men had no inhibitory activity. However, the serum of the parents of two morons, whose serum was inhibitory, also inhibited the action of HCG.The inhibition of gonadotrophic activity by the serum and cerebro-spinal fluid was similar to the action of protein-free pineal extracts.

The isolation and structure of a-corticotropin, a polypeptide of 39 amino acid residues, derived from sheep pituitary glands and possessing an adrenocorticotropic (ACTH) activity of 150 I.V. per rag., have been reported from this laboratory (1-3). The present paper is concerned with various biological properties of the peptide hormone. A. Stimulation of the Adrenal Glands in Normal and Hypopkysectomized RatsExperiments witk Normal Rats.--The increment of adrenal weight in 21-dayold normal male rats induced by the administration of ACTH preparations has been suggested by Moon (4) as a criterion for the assay of ACTH potency. Because various substances and conditions will produce adrenal hypertrophy in the intact animal, this criterion is not specific, and hence, as has been discussed elsewhere (5), this type of assay does not furnish a reliable index of degree of biological potency. It is, however, useful for detecting activity in a preparation, since adrenocorticotropicaUy active preparations should be capable of increasing the adrenal weight in normal animals.The hormone peptide was suspended in peanut oil and S per cent beeswax according to the procedure described by Bruce, Parkes, and Perry (6). Male rats, 28 days of age, of the Long-Evans strain were injected intraperltoneally with 0.1 ml. of the hormone suspension once daily for 4 days, and the --|reals were autopsied 24 hours after the last injection. As Table I reveals, 1 a daily dose of 1S/zg of a-corticotropin for 4 days produced an increase in * Present address:

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