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Search for other papers by G. ALEXANDER in
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SUMMARY
In pregnant ewes, ovariectomized 3 weeks after mating and maintained with progesterone (7 mg./day) injected intramuscularly, there was excessive accumulation of allantoic fluid after 2 months of gestation. The addition of oestradiol benzoate (5 μg./day) or an increase in the dose of progesterone reduced the allantoic fluid volume to normal; this reduction depended on the dose of oestrogen and on the dose ratio of oestrogen to progesterone. Whilst oestrogen reduced allantoic fluid volume to normal, it increased the incidence of 'bovine' type of cotyledons which are not normally seen in ewes 2 months pregnant. The large allantoic volumes were apparently due to the absence of luteal rather than other ovarian tissue, since large volumes were also present in ewes maintained on 7 mg. progesterone/day after corpora lutea had been surgically expressed from the ovaries left in situ. Embryonic survival was adversely affected when corpora lutea were removed from the ovaries, but there was no clear effect on the morphology of cotyledons.
Search for other papers by G. ALEXANDER in
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SUMMARY
Pregnant ewes were ovariectomized 3 weeks after mating, and were injected daily with graded doses of progesterone (0·05–1·35 mg./kg.) for the next 6 weeks. A minimum daily dose of 0·15 mg./kg. was found necessary for the regular maintenance of pregnancy. On the 60th day of pregnancy, when the ewes were killed, there was little or no effect of dose of progesterone on foetal weight, weight and number of cotyledons, weight of uterus and membranes or volume of amniotic fluid. However, at the low doses of progesterone the volume of allantoic fluid was about ten times higher than normal, suggesting that progesterone plays some part in the water balance of the conceptus. In treated ewes, the cotyledons tended to be of the bovine type with foetal tissue enveloping the maternal, which suggests that growth of maternal cotyledons may be limited by the absence of ovaries.
It is suggested that the large variations usually observed in the placental size of sheep, are not due to variations in output of ovarian progesterone, and that the normal daily output of the ovine corpus luteum during the first 2 months of pregnancy is equivalent to at least 15 mg. of subcutaneously injected progesterone.
Search for other papers by D. Guémené in
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Search for other papers by J. B. Williams in
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ABSTRACT
Stimulation of male turkey hypophyses in vitro with chicken (c)LHRH-I, cLHRH-II or porcine (p)LHRH (0·1 μmol/l) using a perifusion technique caused an increase in the release of LH. In this system, cLHRH-II was approximately 2·5-fold more potent than cLHRH-I and pLHRH which were equipotent. The difference was due to a greater amplitude of the response but not to a prolonged action. Hypophyseal desensitization to a subsequent stimulation was induced when the interval between stimulations was 30 min, but did not occur when lengthened to 60 or 120 min.
Injection of a single dose of cLHRH-I or -II in vivo at doses of 10 and 0·1 nmol/kg body weight stimulated increases in the plasma concentration of LH and testosterone initiated within 1 or 10 min after injection respectively. As in vitro, cLHRH-II induced greater responses, which were dose-related, than did cLHRH-I. However, this difference could be attributed to a greater potency of cLHRH-II and to a more prolonged action. At the 10 nmol/kg dose, the shape of the LH response to cLHRH-II changed; it consisted of an initial increase during 10 min after injection, followed by a more sustained phase during which LH levels were still increasing between 20 and 60 min after injection. In contrast, after an injection of cLHRH-I at doses of 10 or 0·1 nmol/kg or cLHRH-II at a dose of 0·1 nmol/kg, LH levels were at a peak within 5 min and thereafter declined gradually. This decrease in LH may therefore simply be related to the disappearance of the LHRH from the circulation or to other unknown actions of cLHRH-II, when high doses are used.
Journal of Endocrinology (1992) 132, 387–393
Search for other papers by J. P. Monson in
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Search for other papers by D. J. Williams in
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The alterations in water homeostasis which accompany human pregnancy provide a unique example of resetting of osmolar control. The changes have inherent interest as a physiological adaptive mechanism, but do they have pathological significance for patients with previously unrecognized disturbance of water balance? In this commentary we highlight briefly the physiological changes in osmoregulation which occur in pregnancy. The possible mechanisms for these changes, including alterations in the metabolism and action of arginine vasopressin (AVP), are described and we attempt to relate these to the rare, but well recognized, phenomenon of exacerbation of subclinical diabetes insipidus in pregnancy. The tentative associations between AVP metabolism, pre-eclampsia and diabetes insipidus are also addressed.
Physiological water retention of pregnancy
Normal pregnancy is characterized by an early decrease in serum osmolality of up to 10 mosmol/kg which continues throughout gestation (Davison, Valloton & Lindheimer, 1981). This hypotonicity is maintained by a decreased osmotic threshold
Search for other papers by J. T. EAYRS in
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Search for other papers by E. D. WILLIAMS in
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In a preliminary study designed to examine the nature of experimentally induced changes in thyroid-pituitary relationships the relative concentrations of radioactive iodide in the goitrogen-blocked thyroid gland and serum (T:S ratio) of normal rats diverged so widely from those reported in the literature (e.g. Vanderlaan & Vanderlaan, 1947; Halmi, 1957) as to suggest the presence of some uncontrolled factor. The possible influence of physical environment, diet and strain of rat, was considered and in the experiment to be described the first of these was standardized, the others providing two variables which were studied in relation to their main effects and interactions.
Six female rats of comparable weight (239 ± 6 g.) from each of five different sources (the term 'strain' is subsequently used for convenience) were assembled and housed at 21 ± 0·5° in ten identical cages each containing three rats from the same strain and on the same diet.
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Search for other papers by I. DONIACH in
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SUMMARY
Rats were hypophysectomized and the left thyroid lobe auto-implanted subcutaneously to the anterior abdominal wall 3 weeks later. They were killed at intervals varying from 2 to 56 days after implantation. Twelve grafts were identified histologically in the twelve animals in which completeness of hypophysectomy was confirmed by serial section of the pituitary bed, extreme lowering of T/S ratio, marked loss of weight of adrenals and testes and loss of body weight. The follicles of the graft showed taller cells than those in the neck and intracytoplasmic PAS-positive droplets.
In a further series of rats production of TSH was suppressed by daily s.c. injections of thyroxine varying from 15 to 100 μg. One thyroid lobe was auto-implanted after 3 weeks' treatment, the thyroxine being continued afterwards. Animals were killed at intervals from 3 to 15 days. Thirty-two grafts were identified in the 36 thyroxine-treated rats. Autoradiographs at 6 and 24 hr. after administration of 50 μc 131I showed a greater iodine uptake in some follicles of the grafts than in any in the neck thyroid at 15 days. Measurement showed thyroid follicular cells in the graft to be twice as tall as those in the neck. It was concluded that the 'take' of thyroid grafts is independent of TSH and that their reparative growth is accompanied by an associated increased organic binding of iodine.
Search for other papers by E. D. WILLIAMS in
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Search for other papers by I. DONIACH in
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SUMMARY
1. The anticoagulant drug phenylindanedione (PID) reduced the uptake of 131I by the rat thyroid as effectively as propylthiouracil (PTU) in a dosage of 0·3 m-mole/kg body weight. The effect of PID lasted for a shorter time, and at smaller doses PTU was much more effective than PID.
2. Chromatography of digested thyroid tissue showed that PID exerts its antithyroid action by blocking the organic binding of iodine.
3. Vitamin K1 did not overcome the antithyroid action of PID. Among other anticoagulants and chemically related compounds tested only phthiocol was found to have an antithyroid effect.
4. In five out of seven patients receiving PID the 48 hr thyroid 131I uptake was at or below the lower limit of the normal range. Three of these patients were retested after stopping PID, in each case the thyroid uptake was markedly increased.
5. The chemical grouping
Search for other papers by A. R. GOLDSMITH in
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Search for other papers by D. M. WILLIAMS in
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The concentrations of prolactin and LH were measured in the plasma of male and female mallards (Anasplatyrhynchos) during the breeding season. The concentration of prolactin in the female birds was low before and during egg-laying, increased threefold (P < 0·001 ) during incubation and returned to basal levels immediately after the young were hatched. The drakes, which do not participate in incubation in this species, had fairly low prolactin levels throughout the breeding period; levels being slightly higher during the incubation phase than at other times but still much lower (P < 0·001) than in the incubating females. Concentrations of LH in the females were high during egg-laying but declined at the onset of incubation. In the drakes levels of LH remained high for much longer and did not appear to decline at a fixed time relative to the reproductive cycle of the female birds. These observations support the view that prolactin is associated with incubation in birds, though the data do not permit a conclusion as to whether an increase in prolactin secretion causes incubation behaviour or is stimulated by it.
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Search for other papers by L Pickavance in
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Search for other papers by G Williams in
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To evaluate the role of neuropeptide Y (NPY), a potent appetite stimulant, in controlling food intake and body weight, we investigated the use of antisense oligodeoxynucleotides (ODNs) to inhibit NPY gene expression in the hypothalamus. We compared the hypothalamic distribution of fluorescein-labelled ODNs administered intracerebroventricularly, and effects on food intake and NPY gene expression, of three different structural modifications of an antisense ODN sequence against NPY. Rats had either the antisense or missense ODNs (24 micrograms/day) or saline infused into the third ventricle by osmotic minipumps for 7 days. The unmodified phosphodiester ODN was not detectable in the hypothalamus after 7 days and had no effects on food intake. The phosphorothioate ODN was widely distributed throughout the hypothalamus but had nonselective effects, with similar changes in food intake and NPY mRNA levels in the antisense and missense groups, and was severely toxic. The propyl-protected ODN appeared to penetrate the hypothalamus well but had no antisense-selective effects on NPY mRNA levels or food intake. Antisense ODNs are increasingly used to inhibit gene expression in vitro and in intact animals. These negative findings underline the need for rigorous evaluation of any effects of antisense ODNs administered into the central nervous system, and raise doubts about the validity of this approach in physiological or pharmacological studies.
Search for other papers by D. A. Carter in
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Search for other papers by T. D. M. Williams in
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ABSTRACT
The influence of endogenous opioids on the posterior pituitary response to stress was investigated by measuring plasma hormone levels in immobilized male and female rats following either acute naloxone treatment or prolonged morphine administration. Naloxone significantly potentiated the oxytocin and arginine vasopressin (AVP) response to immobilization, but in female rats only. The responses of morphine-treated male rats showed differences compared with vehicle-treated controls, although chronic morphine treatment did not reliably alter the oxytocin or AVP responses to immobilization in males or females.
In a further experiment to investigate the role of gonadal hormones in determining the sex difference in responsiveness to naloxone, it was found that acute naloxone treatment significantly potentiated the posterior pituitary response to stress in castrated male rats.
These results extend previous studies showing a sex difference in stress-induced secretion of posterior pituitary hormones, providing evidence of a sexual dimorphism in the endogenous opioid regulation of this response which is partly determined by circulating gonadal hormones.
J. Endocr. (1986) 111, 239–244
