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SUMMARY
In order to obtain exclusive long-term access to both the arterial and venous sides of the ovarian circulation in the ewe, a technique was evolved for vascular autotransplantation of the ovary. The first stage consisted of the preparation of a carotid artery—jugular vein skin tube, with a pouch to receive the ovary and its pedicle. In the second stage, performed at least 2 months later, the left ovary and its pedicle were removed together with an aortic patch which included the orifice of the ovarian artery. The aortic patch was inlaid into the carotid artery to provide the arterial supply to the transplanted ovary; venous drainage was achieved by end-to-side anastomosis of the termination of the middle uterine vein to the jugular vein. The right ovary was removed. The transplanted ovary was shown to have an unimpaired circulation. Ovarian function was demonstrated by histological and behavioural evidence, and by demonstration of a cyclical secretion of progesterone. The rate of progesterone secretion was < 5 μg./hr. at oestrus and rose to approximately 200 μg./hr. in the luteal phase of the cycle which is within the range reported for the ovary in situ.
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SUMMARY
[4-14C]Progesterone was administered intravenously to five ewes with chronic bile-duct fistulae and to one intact animal. The mean percentage of the injected dose, calculated as 'excretable' when extrapolated to infinite time, was 95·5% (range: 81–104%). The time of excretion of half the radioactivity as estimated from excretion curves of the accumulated activity was 2·9 hr. (range: 1·5–7·8 hr.). The mean urinary 'excretable' fraction was 25·5% (range: 8–53% of the injected dose, that of bile was 70·0%. Urine contained relatively more of the polar material (presumable double conjugates of the metabolites) than bile.
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Search for other papers by H. J. H. MACFIE in
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The roles of androgen and oestrogen in the perinatal and postpubertal stages of developmen on the masculinization of female patterns of growth have been investigated in several experi ments in rats.
A stimulatory effect of testosterone on subsequent growth and efficiency of food utilization was only observed when administered perinatally to intact females as the propionate ester. Thus females which were untreated (or androgenized) perinatally and ovariectomized at weaning failed to grow more rapidly or utilize food more efficiently when treated with mixed testosterone esters from 36 to 38 days of age. Also autoimmunity to luteinizing hormone releasing hormone (LH-RH) had little effect on the growth or efficiency of food utilization of male rats, although testicular development was grossly affected.
An inhibitory effect of oestrogen on subsequent growth and efficiency of food utilization was demonstrated by surgical ovariectomy and by autoimmunity to LH-RH. Also perinatal administration of oestradiol benzoate to intact female rats depressed growth below that of untreated intact litter-mate females until about 50 days of age. Then oestradiol benzoate-treated female rats grew to a larger size than untreated intact litter-mates but not to a heavier weight than untreated litter-mate females which like the oestradiol benzoate-treated females, were ovariectomized at 18–21 days of age. Both of these groups of female rats differed markedly in weight gain from females which were perinatally androgenized and ovariectomized at weaning. The effects of androgenization and ovariectomy on weight gain were comparable and additive in female rats fed restrictedly or ad libitum.
Nevertheless, androgenized + ovariectomized female rats fed restrictedly or ad libitum failed to grow as rapidly as male rats. Some additional factor(s) prevents complete masculinization of the female pattern of development. The stimulatory effects of androgenization and ovariectomy on the growth of females appear to be related to endocrine mechanisms controlling the onset of pubertal changes in somatic development.
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Search for other papers by D. T. BAIRD in
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SUMMARY
The transplanted ovary preparation in the ewe permits long-term access to both the arterial and venous sides of the ovarian circulation in the unstressed, unanaesthetized animal. However, these animals are not completely normal, as the separation of the ovary from the uterus results in ovarian cycles with a prolonged luteal phase and the infrequent manifestation of behavioural oestrus. Treatment with exogenous gonadotrophins made it possible to carry out direct infusion experiments on the transplanted ovary on a more uniform basis. The effect on ovarian blood flow and on ovarian steroid secretion following the infusion of ovine luteinizing hormone (LH), ovine follicle-stimulating hormone (FSH) or ovine prolactin directly into the arterial supply of the transplanted ovary of the ewe is described. Four infusions of each of the three ovine pituitary gonadotrophins were made into the ovary at rates varying from 0·1 μg./hr. to 1000 μg./hr. LH infusions produced an increase in both ovarian blood flow and steroid secretion at all dosage levels employed. Androstenedione showed the greatest increase (600%) in secretion rate after LH, followed by testosterone (400%), oestradiol (more than 50%) and progesterone (less than 50%). Progesterone however showed the greatest increase in terms of mass of steroid secreted. There was no measurable change in the secretion of oestrone. Ovarian blood flow increased by at least 20% (range 20–125%) within 1 hr. of beginning the LH infusion. On the other hand FSH and prolactin infused at the same or at a higher rate than LH, had essentially no effect on ovarian blood flow or steroid secretion rate. In two out of four FSH infusions there appeared to be a transient fall in progesterone secretion rate. The infusion of 0·9% NaCl solution into the ovary as a control had no effect on blood flow or on steroid secretion.
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Search for other papers by J. A. McCRACKEN in
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SUMMARY
Secretion rates of ovarian steroids were measured in five ewes in which the left ovary was transplanted to the neck. Progesterone, 20α-dihydroprogesterone, androstenedione, testosterone, oestrone and oestradiol-17β were measured in samples of ovarian venous blood collected twice weekly for six periods of 4–9 weeks. The secretion of progesterone (range < 2–804 μg./hr.) showed some cyclical variation in four collection periods with a minimum estimated cycle length of 20 days. 20α-Dihydroprogesterone was present in quantities of about 1/50th of that of progesterone. The maximum secretion of oestradiol-17β (up to 250 ng./hr.) occurred at the same time as the minimum secretion of progesterone. The secretion of oestrone (0–88 ng./hr.), androstenedione (59–159 ng./hr.) and testosterone (20–90 ng./hr.) followed that of oestradiol-17β. In two animals there was a constant high secretion of progesterone throughout the collection periods, indicating the persistence of a corpus luteum. None of the ewes with transplanted ovaries showed behavioural oestrus regularly. These changes of ovarian function after transplantation to the neck could be explained by physical separation of the ovary and the uterus.
On seven occasions systemic administration of pregnant mare serum gonadotrophin (PMS, 750–1000 i.u.) was followed by a marked rise in the secretion rate of oestradiol-17β, androstenedione and testosterone. There was a progressive increase in the secretion of progesterone beginning about the 5th day after PMS in three experiments when the secretion was below 25 μg./hr. in the control samples.