Fifteen days after hypophysectomy of rats the concentrations of ascorbic acid (AA) in adrenals, liver, blood and urine are lower than in normal rats or in rats 1 day after hypophysectomy. Despite the low levels the percentage AA depletion after administration of ACTH and the subsequent repletion to the pre-ACTH level are normal. Lack of corticosteroids is not the cause of the low AA levels, as shown by experiments in 15 days adrenalectomized rats and in rats treated with low doses of dexamethasone.Fifteen days treatment with high doses of dexamethasone lowered the AA concentrations in adrenals, liver and blood. Treatment with long-acting ACTH maintained adrenal weight but not adrenal and blood AA. A high dose of ACTH lowered these levels. The administration of AA markedly increased the AA levels in blood, but did not normalize its concentration in the adrenals, not even when the size of the adrenals was maintained by treatment with long-acting ACTH. Growth hormone, in particular when administered together with long-acting ACTH, markedly raised the AA concentration in the adrenals but hardly affected the AA blood level. Rats with high blood levels of prolactin induced by pituitary grafts in the kidney also had clearly higher AA levels in adrenals, but not in blood. These results indicate that, although acute AA release from the adrenal is caused by ACTH, AA uptake to a certain concentration is not controlled by the pituitary gland, and above this concentration is promoted by growth hormone and prolactin. In the liver AA release may also be caused by ACTH but the AA production is promoted by other as yet unidentified pituitary factors.In rats 15 days after hypophysectomy the adrenals are markedly atrophied and contain little ascorbic acid (AA) both absolutely (mg/adrenal) and rela¬ tively (mg/100 g adrenal). This was described by Stähelin et al. (1965) and confirmed by Overbeek (1981a,b). It was to be expected that the atrophied adrenals would contain only small amounts of AA but the fact that the concentration is well below normal was unexpected and requires an explana¬ tion.Several explanations are conceivable such as: a decreased supply of AA to the adrenals as a con¬ sequence of an increased urinary excretion of AA; or a decreased production of AA; or a decreased ability of the adrenal to store A A.Such possibilities have been explored in the present study.It was also studied if the lowered corticosterone production in the adrenals influences AA levels in adrenals, blood and liver and if one of the lacking pituitary hormones could be held responsible for the abnormal AA levels in the long-term hypophysectomized rats. Materials and MethodsThe experiments were carried out with male Wistar rats purchased from TNO, Zeist, The Netherlands (body weight about 300 g). Hypophysectomy was performed by the parapharyngeal route. Ascorbic acid (AA) was deter¬ mined in adrenals with the dichlorophenol-indophenol method (USP XX) and in blood, liver and urine with the dinitrophenylhydrazine (DNPH) method described by György &...

Lynestrenol is a potent oral pregestagen. The oral activities in the Clauberg and Corner & Allen tests are of the same order as that of subcutaneously administered progesterone. No effect was found in the tests for deciduomagenic activity in the mouse and for the maintenance of pregnancy in the rat. Lynestrenol has a marked inhibitory action on ovulation in the rat. This effect can be enhanced by low doses of oestrogen, which themselves are inactive in this respect. The main cause of this effect seems to be an inhibition of the development of the follicles. Lynestrenol is a weak oestrogen with an activity of about 1–2% of that of ethinyloestradiol. Its effects on fertilized ova in the rat are in agreement with what could be expected from its oestrogenic activity. There is little or no effect on nidation. Lynestrenol is a weak androgen, the oral activity in the rat amounting to 1/3–1/4 of that of methyltestosterone. 5. Acute and chronic toxicity studies demonstrate the absence of any general toxicity.

Several gonadotrophin preparations, HMG (Human Menopausal Gonadotrophin), HPG (Human Pituitary Gonadotrophin) and NIH FSH S1 (a FSH preparation distributed by the National Institute of Health) were investigated for biological activity, using three methods of assay. The rat augmentation test, specific for FSH, and the rat seminal vesicle weight test, specific for ICSH both gave statistically valid results. The potencies were expressed in terms of the IRP (International Reference Preparation for HMG), and the International HCG Standard respectively. The gonadotrophic activity as determined by the rat uterine weight method was expressed in terms of IRP and in terms of the International HCG Standard. Good agreement was found between the results in the uterine weight method and the seminal vesicle test, suggesting a strong ICSH dependence for the former. On the other hand, the results of the uterine weight method and the augmentation test were not in agreement. Consequently the rat uterine weight method must be regarded as completely unsuitable for the assay of FSH-activity.Among the three test methods studied, the augmentation test appears to be the only one suitable for the assay of the FSH content of gonadotrophin preparations for clinical use. Fractionation of HMG with ethanol led to preparations with high FSH activity, 200 to 300 times that of IRP, but with little ICSH activity. Most of the ICSH was concentrated in other fractions, indicating that both hormones can be separated. In starch gel electrophoresis these fractions showed different patterns.

A comparison was made of the anabolic (myotrophic) and androgenic properties of 1. the phenylpropionates of testosterone (17β-hydroxyandrost-4-en-3-one) and nandrolone (17β-hydroxy-estr-4-en-3-one) and 2. the decanoates (= caprinates) of testosterone and nandrolone after the subcutaneous injection of a single dose into rats. The question to what extent scientifically justifiable potency ratios can be calculated is discussed. The difference in activities can in any case, be convincingly shown by means of graphs. Both nandrolone esters were relatively much more anabolic and less androgenic than the corresponding testosterone esters. The decanoates had a much longer duration of action than the phenylpropionates.

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