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R. C. JONES

The oral administration of 5 mg. quinestrol (3-cyclopentyl ether of ethinyl oestradiol) has been shown to inhibit ovulation in normal women (Skerlavay & Epstein, 1967); presumably the quinestrol blocks the release of gonadotrophins. In parabiotic rats, Giannina, Steinetz & Meli (1967) used daily administration of oral quinestrol to block hypersecretion in the castrated male.

In the present study, hemicastrated adult female rats were used to test the prolonged pituitary blocking effect of a single oral dose of quinestrol. At the time of the unilateral ovariectomy, the rats recieved 1 mg. quinestrol by gavage. Animals were killed at approximately 2-day intervals after operation. At autopsy the remaining ovary (the left) was removed and weighed. Hemicastration produces a compensatory hypertrophy of the remaining ovary which may be prevented by oestrogen administration (Peterson, Edgren & Jones, 1964). If quinestrol is long-acting when given orally and suppresses pituitary gonadotrophic function it should decrease this

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R. C. JONES

Since the effects of injecting oxytocin into ewes just after artificial insemination were to be tested, the experiment described was designed to determine a range of doses of synthetic oxytocin which would produce 'milk let-down' in ewes. Intramuscular injection was chosen as the most practical route of administration since it was planned to use a large number of sheep in the subsequent experiments.

Martinet & Denamur (1960) have shown that both massage of the udder and i.v. injection of 10–50 m-u. oxytocin cause similar increases in intramammary pressure in goats and sheep and Debackere & Peeters (1960) and Debackere, Peeters & Tuyttens (1961) have shown that intramammary pressure in ewes was increased by distension of the vagina; a similar response was obtained by i.v. injection of 20–50 m-u. oxytocin. Since Fitzpatrick (1960) had found that oxytocin injected i.v. was 2·25 and 2·5 times more potent than when injected i.m., the

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C. T. JONES

Nuffield Institute for Medical Research, University of Oxford, Headley Way, Oxford, 0X3 9DS

(Received 20 February 1976)

During the latter third of gestation undisturbed foetal sheep with chronically implanted vascular catheters have higher plasma adrenocorticotrophin (ACTH) concentrations than adult sheep (Boddy, Jones, Mantell, Ratcliffe & Robinson, 1974; Jones, Boddy, Robinson & Ratcliffe, 1975a). This is probably the result of a higher rate of secretion from the foetal pituitary (Jones, Luther, Ritchie & Worthington, 1975 b). The plasma glucose concentration of foetal sheep is substantially lower than that of mature sheep (Shelley, 1973). Since hypoglycaemia is a potent stimulus for ACTH secretion (Yalow, Varsano-Aharon, Echemendia & Berson, 1969; Vague, Oliver & Vague, 1972) a correlation between the plasma glucose and ACTH concentrations in pregnant and foetal sheep has been sought.

Plasma samples were collected from 60 pregnant and foetal sheep with chronically implanted carotid arterial catheters as previously described (Boddy et al.

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C. T. JONES and D. RURAK

Nuffield Institute for Medical Research, University of Oxford, Oxford, 0X3 9DS

(Received 11 March 1976)

Vasopressin is considered an important hormone controlling adrenocorticotrophin (ACTH) secretion under some conditions (De Wied, Bohus, Ernst, de Jong, Nieuwenhuizen, Pieper & Yasumura, 1968). Its infusion into dogs at pharmacological but not physiological doses increases plasma ACTH concentration (Andersen & Egdahl, 1964). It behaves as a corticotrophin-releasing factor on incubation with anterior pituitary cells (Portanova, Smith & Sayers, 1970). Moreover a neuroendocrine vasopressin pathway possibly associated with ACTH secretion has been proposed (Parry & Livett, 1973). During hypoxaemia in the foetal sheep there is a rise in both plasma ACTH and vasopressin (Alexander, Britton, Forsling, Nixon & Ratcliffe, 1973; Boddy, Jones, Mantell, Ratcliffe & Robinson, 1974b; Rurak, 1976). Thus the possibility that a rise in foetal plasma vasopressin is responsible for the increased secretion of ACTH during hypoxaemia has been investigated. Foetal and maternal vascular

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I. CHESTER JONES and C. C. ROBY

SUMMARY

Male adult mice, 80 days after hypophysectomy, show approximately the same pattern of sodium and potassium intake and sodium, potassium and water output as normal mice. The healthy remnant of adrenal cortex left after the operation is thought to be responsible for the day-to-day competence of the hypophysectomized animal in salt-electrolyte metabolism. The histology of the cortex is described and it is shown that, with the injection of ACTH, a cortex of normal appearance can be regenerated from the persistent zona glomerulosa of the long-term hypophysectomized mouse.

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ESTHER C. JONES and P. L. KROHN

SUMMARY

Hypophysectomy in the mouse (A, CBA, RIII and RIII × CBA strains) significantly retards, but does not wholly prevent, the normal progressive loss of oocytes from the ovary. The proportion of follicles judged to be normal on histological criteria rises from levels of 50–60% to levels of 60–75%. CBA strain mice which normally lose oocytes faster than the other strains still show this difference after hypophysectomy.

The extent to which the ovaries of hypophysectomized mice retain their normal function after more than 300 days in a gonadotrophin-free environment has been tested by transplanting them orthotopically into normal female hosts. In all cases, the grafts responded to gonadotrophin supplied by the new host and in the favourable environment provided by a young host produced normal litters as satisfactorily as transplanted normal ovaries.

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S. J. Arkinstall and C. T. Jones

ABSTRACT

The regulatory factors controlling uterine activity during pregnancy remain unclear in many species. Since myometrial relaxants raise intracellular cyclic AMP, modulation of signalling pathways coupling cell-surface receptors to adenylate cyclase activation could be an important site for control. To assess the functional activity of the stimulatory GTP-binding protein Gs we have measured adenylate cyclase activation by GTP, its non-hydrolysable analogue guanosine 5′-(β-γ-imido)triphosphate (Gpp(NH)p), fluoride, forskolin and manganese in a 50 000 g membrane fraction prepared from the myometrium of non-pregnant, mid-pregnant (30–32 days) and late-pregnant (62–66 days) guinea-pigs (full term 67±2 days). While forskolin- and manganese-dependent enzyme activation was unaltered by pregnancy, maximal stimulation by Gpp(NH)p and fluoride was enhanced by up to 200%. Recovery of adenylate cyclase activity in the 50 000 g fraction was essentially constant at 20–24% of the total activity throughout pregnancy, and thus cannot explain the increases observed. Since guanine nucleotides and fluoride stimulate adenylate cyclase through activating Gs, and forskolin and manganese act at the level of the catalytic unit, these data are consistent with a pregnancy-related increase in Gs functional coupling while adenylate cyclase activity is unaltered. These observations suggest a physiological regulation of myometrial Gs activity during pregnancy which could facilitate hormonal stimulation of adenylate cyclase and contribute to uterine quiescence by increasing uterine sensitivity to relaxants.

Journal of Endocrinology (1990) 127, 15–21

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ESTHER C. JONES and P. L. KROHN

SUMMARY

Although unilaterally spayed mice can produce litters almost as large as those produced by normal mice, their reproductive lifespan is curtailed and the total number of offspring born is about halved.

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B. T. PICKERING and C. W. JONES

SUMMARY

A method is described for the preparation of isotopically pure [3H]oxytocin and [3H]vasopressin from the pooled posterior pituitary glands of groups of four or five rats after the intracisternal injection of [3H]tyrosine. Hormones were separated from deproteinized neurohypophysial extracts by chromatography on Amberlite CG-50, and further purified by chromatography on carboxymethylcellulose. In this way, samples of the hormones were obtained with a very high degree of isotopic purity. The method is suitable for studying the effects of stimuli to the hypothalamo—neurohypophysial system on the biosynthesis and transport of the hormones.

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ESTHER C. JONES and P. L. KROHN

SUMMARY

1. A surgical technique for the orthotopic transplantation of the ovaries in mice is described and its immediate and long-term difficulties are discussed.

2. The shortened reproductive lifespan of mice which have received such grafts is due primarily to the loss of oocytes during the immediate postoperative period before a new blood supply has developed. Figures are given for the loss, which may extend to between a half and three-quarters of the total complement of oocytes.