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H. HELLER

Estimations of urine volumes and inulin U/P ratios in newborn rats after the administration of 4·5 ml. water and 10 mU. vasopressin/100 g. body weight failed to show an antidiuretic response comparable to that produced in adult controls. When body surface was chosen as the basis of dosage, relatively larger amounts of water were given to newborn rats. These produced an increase in the rate of urine flow (which, however, still remained well below the adult level), but an inhibitory effect of vasopressin again could not be demonstrated.

Experiments on older rats (up to 4 weeks of age) showed that an antidiuretic effect of vasopressin comparable to that of adults develops only after several weeks of postnatal life, approximately at the same time as a full diuretic response to water could be obtained.

When 10 mU. vasopressin/100 g. body weight was injected both adult and newborn rats excreted about 10% of this dose.

It is suggested that vasopressin acts less effectively in newborn rats because for some time after birth the kidney is less responsive to the posterior pituitary antidiuretic hormone than in adults.

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H. HELLER

SUMMARY

Uteri of the marsupial species Setonix brachyurus suspended in a solution with a cation concentration similar to that of Setonix plasma ultrafiltrate, responded to oxytocin, arginine-vasopressin (AVP) and arginine-vasotocin at all stages of the oestrous cycle (28 days) and gestation (27 days). In cyclic intact non-pregnant animals the potency of AVP in evoking contractile responses of the uterus was greater than that of oxytocin when the myometrium was oestrogen-dominated, i.e. from about day 19 to about 2 days after oestrus. In contrast, during the luteal phase (day 7–18) the uterine muscle was much more responsive to oxytocin than to AVP, although the threshold concentration for oxytocin was raised. The uteri of bilaterally ovariectomized quokkas responded more markedly to AVP than to oxytocin after treatment of the animal in vivo with an oestrogen. The responsiveness of uteri of progesterone-treated ovariectomized quokkas to vasopressin was equal to or less than their responsiveness to oxytocin.

The response of the pregnant Setonix uterus to oxytocin was always greater than that to AVP, even late in pregnancy when at the corresponding stage of the oestrous cycle in the non-pregnant quokka (day 19–23) the myometrium was more responsive to AVP than to oxytocin. At earlier stages of pregnancy there were indications of a similar degree of progesterone block to oxytocin as during the luteal phase in non-pregnant Setonix.

It has frequently been assumed that the endocrine milieu in marsupials is the same during the oestrous cycle and in pregnancy. The present results suggest that there are differences.

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M. GINSBURG and H. HELLER

1. The antidiuretic potencies of blood, serum and plasma obtained from various parts of the cardiovascular system of rats were compared.

2. External jugular blood was found to have higher activity than blood from the other sites. After hypophysectomy the antidiuretic potency of external jugular blood was much diminished.

3. The antidiuretic activity of hepatic and renal venous blood was lower than that of arterial blood, suggesting that antidiuretic hormone is removed from blood during passage through the splanchnic vascular area or the kidneys, or both.

4. The antidiuretic potency of blood was shown to increase with the volume of blood withdrawn.

5. Ether anaesthesia increased the antidiuretic activity of external jugular blood.

6. The antidiuretic activity of carotid serum when given subcutaneously was higher than that of carotid plasma. This difference was not seen after intravenous injections.

7. In sheep and in mice, plasma of blood from the external jugular veins had more antidiuretic effect than plasma from other sites.

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M. GINSBURG and H. HELLER

1. A method has been described for the assay of vasopressin by intravenous injection in unanaesthetized rats.

2. The choice of parameters for the expression of antidiuretic responses has been studied in rats and rabbits.

3. It has been shown that the sensitivity of rats to injected vasopressin is independent of the water load within the range of 6–9% of the body weight.

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M. GINSBURG and H. HELLER

1. The decrease of antidiuretic potency in the blood was studied in anaesthetized rats after the intravenous injection of vasopressin (100 mU/100 g) and was shown to follow an exponential course.

2. Removal of the kidneys retarded the rate of disappearance of injected vasopressin from the circulation, and so did tying of the coeliac and mesenteric arteries.

3. In rats in which the kidneys had been removed and the coeliac and mesenteric arteries had been tied, the disappearance of vasopressin was almost entirely prevented.

4. It was concluded that under the experimental conditions used, the extraction of vasopressin was almost complete after the passage of blood through the kidneys and the splanchnic vascular bed.

5. The kidneys accounted for about 50 % of the vasopressin cleared, and the splanchnic vascular area for at least 40 %.

6. The antidiuretic activity found in the urine after the intravenous injection of vasopressin into unanaesthetized rats was equivalent to 6·7 % of the dose administered.

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H. HELLER and K. E. BLACKMORE

Antidiuretic activity has been assayed by intravenous injection of the test fluid into unanaesthetized mice to which three doses of water had been given by stomach tube. The method seems to be suitable for doses of the approximate range of 10 to 50 μU. vasopressin 10 g./body weight.

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E. M. RODRIGUEZ and H. HELLER

SUMMARY

Acetic acid extracts of toad choroid plexuses had an antidiuretic effect in water-loaded ethanol-anaesthetized rats, whose pattern was similar to that produced by toad neural lobe extracts and by arginine vasopressin. The antidiuretic activity of the choroid plexus extracts was completely abolished by treatment with sodium thioglycollate. Antidiuretic activity per milligram choroid plexus was about four times higher in the plexus of the third ventricle than in the plexus of the fourth ventricle. The antidiuretic activity of both choroid plexuses increased progressively during the summer and autumn and reached its peak in October; it then fell to very low or undetectable levels during the middle of the winter and spring.

The choroid plexuses also showed seasonal variations in their ultrastructural organization, which might be related to the seasonal variations of their antidiuretic activity.

The origin of the substance(s) responsible for the antidiuretic activity in the choroid plexuses is discussed.

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B. T. PICKERING and H. HELLER

SUMMARY

Two peptides with uterotonic activity have been isolated from the pituitary gland of a holocephalian elasmobranch fish: Hydrolagus collei. One of them had an amino acid composition compatible with that of oxytocin itself, and also had the pharmacological properties of this hormone. The other peptide which was present in much smaller amounts was basic by chromatography and had the pharmacological characteristics of [8-arginine]-oxytocin. It was not completely purified because of the small amount available, but its amino acid composition was in accord with that of vasotocin. The implications of the presence of oxytocin in such a primitive fish on the phylogeny, and hence probably the evolution, of neurohypophysial hormones are discussed.

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S. M. A. ZAIDI and H. HELLER

Three groups of workers (Heller, Hasan & Saifi, 1968; Vorherr, Bradbury, Hoghoughi & Kleeman, 1968; Unger & Schwarzberg, 1970) have found that stimuli which are known to release endogenous vasopressin (vagal stimulation, haemorrhage, barbiturate anaesthesia) raised the antidiuretic activity (ADA) in the cerebrospinal fluid (CSF) of experimental animals (rabbits, dogs). The nature of the stimuli, the fact that the ADA was abolished by thioglycollate and the recent finding of neurophysin in the CSF (Robinson & Zimmerman, 1973) indicate strongly that the ADA was exerted by vasopressin. However, it is not clear whether the hormone is directly secreted into the CSF by juxtaependymal processes of neurosecretory neurones as suggested by morphological evidence (for references see Heller et al. 1968; Heller & Zaidi, 1974) or whether it reaches the CSF from the blood.

Heller et al. (1968) and Vorherr et al. (1968) have tried to solve this problem by administering vasopressin intravenously

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H. C. MORSE and C. G. HELLER

SUMMARY

By the employment of an improved histochemical technique, frozen sections from human testicular biopsy specimens were examined for 3β-and 17β-hydroxysteroid dehydrogenase (HSD) activity, before, during, and after administration of 25 or 50 mg testosterone propionate per day to normal men. This administration strongly suppressed Leydig cell HSD activity and caused these cells to be transformed into fibroblast-like cells. After cessation of administration, the Leydig cells recovered morphologically and so did, simultaneously their 3β- and 17β-HSD activity. It is concluded that histochemically detectable 3β- and 17β-HSD are under gonadotrophin control and change with alterations in Leydig cell function. The morphology or 3β- and 17β-HSD are therefore probably acceptable as indicators of Leydig cell function in reproductively normal men.