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Recently, the F. S. H.-content of hypophyses of male rats was found to be more than five times as high as that of the female glands. Oestradiol benzoate (50 μg. daily) caused a substantial decrease in F. S. H. in males, but in females no further decrease of the low level was achieved (Paesi et al., 1955). Testosterone propionate (2 mg. daily) appeared to increase the F. S. H.-content in male rats even though it was high initially (Hoogstra & Paesi, 1957). These data were obtained by injecting a saline extract of the pooled and homogenized hypophyses subcutaneously into hypophysectomized immature male rats which received in addition an overdose of I. C. S. H. (chorionic gonadotrophin). One testis was removed before treatment. The increase of the testicular weight served as a measure of the F. S. H.-content.In two respects these results were at variance with those obtained previously by

In concluding his recent article on ovarian therapy, Graves1 voices the hope that "ovarian extracts, now admittedly feeble and inconstant in their action, will under the direction of research be produced of such potency as to be of constant specific value in the treatment of a limited number of functional pelvic disorders."From this, as well as from other American publications on the subject, we have gathered the impression that the investigations2 done in our own laboratory during the last two years have not become widely known. They are based on fundamental and important American research and may be considered a continuation of such research.Our work led to the preparation of a water-soluble hormone, which in minimal amounts produces strong biologic effects. We gave it a distinctive name to be able to include in its definition a certain degree of purity; i. e., a preparation is named

Dogs that are treated with pituitary extracts develop a kind of diabetes which manifests itself first in glycosuria, and later in damage to the pancreatic islets. This reaction, however, is not found in all kinds of animals. There may well be species differences in sensitivity, and if these originate in the islets of Langerhans the sensitivity of the more resistant animals (e.g. of rats), might be enhanced by measures to diminish the activity of the pancreas. Marx, Anderson, Fong & Evans [1943] removed large parts of the pancreas of rats to this end, and found that the slight glycosuria which they obtained became more severe when the animals were subsequently treated with a hypophyseal preparation. As a highly purified growth-promoting extract was used for this purpose, the experiments once more indicate a relation between the growth-promoting and the 'diabetogenic' functions of the hypophysis.

In previous experiments made in this laboratory it was found, that the F. S. H.-content of the hypophysis of normal rats cannot be decreased by oestrogen (Gaarenstroom & de Jongh, 1943). Hypophyses of full-grown rats, treated either with high doses of oestrogen or with solvent, were implanted into young hypophysectomized male recipients, injected with an overdose of L. H. (chorionic gonadotrophin). Weight-increase of the testis was a measure for the F. S. H.-content of the hypophysis of the donors.The result did not satisfy us, since it is well-known, that the excess of F. S. H. which will appear in the urine of ovariectomized women can be made to disappear by oestrogen. We were not surprised, therefore, that oestrogen was later shown to be able to diminish the F. S. H.-content, provided that castrateddonors were used (Gaarenstroom et al., 1950). Oestrogen reduces the abnormally high F. S. H.-content of

In previous investigations on the influence of the gonads on the hypophysis we described the effect of oestrogen on the follicle-stimulating hormone (F. S. H.)-content of the hypophyses of adult female and male rats (Gaarenstroom et al., 1943; Paesi et al., 1950, 1951). These determinations were carried out by implanting one or half a hypophysis into the abdominal cavity of immature hypophysectomized male recipients and treating these animals with 5 I. U. of human chorionic gonadotrophin (H. C. G.) daily. This amount was considered to be an overdose and, thus, to have a maximum interstitial-cell-stimulating hormone (I. C. S. H.)-effect. One testis of each recipient was removed before implantation and treatment started, the other at autopsy. Differences in the increase of the testis weight in the different groups were considered to be due to the differences in the F. S. H.-content of the implanted glands, since all recipient testes had

The Netherlands Society of Endocrinology has taken an initiative which needs no justification and scarcely any elucidation: its intention is to foster the living memory of the great Ernst Laqueurby the periodic organization of Laqueurlectures. Held as they will be by leading international figures in the world of experimental endocrinology they will doubtless be classics of strictly scientific exposition on current questions in endocrinology; their sights will be set high. They will be in honour of Laqueurbut will no doubt fail to conjure up his spirit. Therefore it seems a fortunate idea to endow the first lecture in this series with a somewhat different character: as one of the few who today can still provide what one might call an eye-witness account, I want to take you back to the period of some twenty years, just before World War II: the heyday of experimental endocrinology at the

The influence of high doses of testosterone propionate (1 or 2 mg. daily) on the pituitary F. S. H.- and I. C. S. H.-content has recently been described in two separate papers (Hoogstra & Paesi, 1957; Paesi, De Jongh & Willemse, 1958). F. S. H. was found to be increased in all kinds of donors with 2 mg., i. e. in intact and gonadectomized males and females. The most marked increase was recorded in intact females where the initial content is low. The I. C. S. H.content was decreased in all groups of donors, but much lower final values were obtained in intact than in gonadectomized animals.The investigation on the effect of testosterone on the gonadotrophic function of the hypophysis has since been continued by determining the influence of more «physiological» dosages: 100 μg. of testosterone propionate daily on the F. S. H.- and I. C. S. H.-content. Since

There is a species difference in the effects of growth hormone on the carbohydrate metabolism of animals. In normal dogs (Young, 1953; Campbell et al., 1954; Chaikoff et al., 1956; Randle, 1957) and cats (Randle, 1957) growth hormone has a »diabetogenic« action.This is probably also the case in man, since acromegalic patients become diabetic. After the successful experiments of Knobil & Greep(1955, 1956) with rhesus monkeys it is obvious that ineffectiveness of bovine growth hormone preparations results from a human species specificity.In normal guinea-pigs (Pages, 1956) and rats, however (Young, 1953; Abrams et al., 1953; Emerson, 1955; Randle, 1957), growth hormone does not induce diabetes; on the contrary, growth hormone lowers the blood sugar levels (Milman & Russell, 1949), prevents a normal rise in blood sugar after a glucose load in hypophysectomized rats (Gaarenstroom, Hublé & de Jongh, 1949 a) as well as in normal rats (Maassen

In a paper dealing with the pituitary I. C. S. H.- and F. S. H.-content of immature male and female rats (Hoogstra & Paesi, 1955) the I. C. S. H.-content of the young glands was found to be much lower than that of adult hypophyses. This was not considered surprising, since young glands are much smaller. Various findings, however, made us doubt, whether any reliance could be placed on the pituitary gonadotrophin content based on differences in weight. Indeed, the relationship is often an inverse one. For example: the F. S. H.content of hypophyses from immature females is much higher than that of the hypophyses from adult females, although the latter are approximately four times as heavy (Hoogstra & Paesi, 1955). In males the F. S. H.-content is highest in the adult, even per mg. gland (as can be seen from the various data); here, testicular androgen, which tends to

It is well known that in the field of carbohydrate metabolism certain relations exist between hypophysis and pancreas. Shortly after learning the possibility of provoking diabetes by means of alloxan we undertook in this laboratory a study of the changes which this artificially induced diabetes undergoes when the test rats are deprived of their hypophysis (Gaarenstroom & de Jongh, 1946, Gaarenstroom, 1947, Gaarenstroom, de Jongh & Polder, 1946, and Gaarenstroom, in press).The symptoms of the disease (the high sugar-concentration in the blood and the excretion of sugar) were found to undergo a marked decrease, and might even entirely vanish, but, as the reaction of the animals upon the administration of sugar clearly showed, the metabolic disturbance of the diabetic animal remained the same. It also became clear that the improvement was, partly at least, a real one, and certainly not entirely a delusive impression caused by the circumstance that

Some years ago Gaarenstroom & de Jongh(1943, 1946) supplied biologicalevidence for the joint presence of two gonadotrophic hormones in the hypophysis of the rat. To make the following exposition more easily understandable we will briefly recapitulate the arguments that have led to this conclusion.It is generally known that in rats the gonadotrophic potency of the hypophysis decreases when the animals are treated for some time with oestrogens. When such animals had received daily 0.2—0.5 mg. oestradiol during a fortnight, the growth their hypophyses produced of the testes of the hypophysectomized young male recipients in whose abdomen they were grafted, appeared to lag behind the growth that was obtained by means of the hypophysis of an untreated donor. As we knew that the testis requires two substances, viz. the substance described under the name FSH and another one, which is called ICSH, for its growth, we repeated the

The experiments of Young(1945) have shown that injections of growth-promoting hypophyseal extracts may cause diabetes in dogs. The way in which this effect is produced, has not yet been fully elucidated, but it may be due to an overstimulation of the insulin-production by the pancreas, resulting in a lesion of the pancreatic islets. This view is supported by the fact that stimulation of the insulin production by other agents, e. g. by means of continuous or frequently repeated dextrose infusions, also leads to a lesion of the islets (Woerner, 1938, and Dohan et al., 1948).The stimulation of the insulin production might be a direct or an indirect effect of the extract. In the first case the extract would have a »pancreotrophic« effect, in the second case the effect might be due to interference with carbohydrate consumption. Arguments in favour of the second supposition were obtained in experiments which