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R. L. W. AVERILL
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SUMMARY

Rats bearing bilateral thermal lesions placed lateral to the paraventricular nuclei were unable to lactate. Replacement therapy with prolactin alone induced partial lactation after subsequent pregnancies, provided the hormone was given for 4–8 days before or after parturition. Once established, these induced lactations persisted despite cessation of hormone injections.

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D. R. Grattan
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R. L. W. Averill
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ABSTRACT

A nocturnal surge of prolactin secretion occurs in the dark period preceding parturition in the rat. The aim of this study was to examine the role of the placenta in the control of this prolactin surge. Plasma prolactin and progesterone were measured by radioimmunoassay in serial blood samples collected after surgical removal of conceptuses during late pregnancy, and after intracerebroventricular (i.c.v.) injection of placental lactogen (PL) before the prolactin surge.

In intact control animals, prolactin secretion remained low until a nocturnal surge of secretion occurred in the dark period preceding parturition, peaking at 269±51 (s.e.m.) μg/l at 03.00 h on day 21. Progesterone levels fell from > 200 nmol/l on day 19 to <40 nmol/l by 12.00 h on day 20 of pregnancy. PL levels during late pregnancy were modified by partial or complete removal of conceptuses at 10.00 h on day 19 of pregnancy. Removal of all but one or two conceptuses did not change the normal pattern of prolactin or progesterone secretion. Removal of all conceptuses, however, induced a large nocturnal surge of prolactin secretion, peaking at 211·7±78 μg/l at 03.00 h on day 20, 24 h earlier than the surge in intact animals. Progesterone levels after removal of all conceptuses fell to <40 nmol/l by 23.00 h on day 19, approximately 12 h before the decline in intact animals. Maintenance of increased progesterone levels after conceptus removal using silicone tubing implants significantly (P <0·05) reduced the peak of the premature prolactin surge to 79·7 ±18 μg/l at 05.00 h on day 20. To determine whether PL could act at the hypothalamic level to inhibit the prolactin surge, human PL was injected into the lateral ventricle. PL injected i.c.v. at 17.00 h on day 7 of pregnancy completely abolished both the expected diurnal and nocturnal prolactin surges in the subsequent 24 h. By contrast, the same treatment on day 20 of pregnancy had no effect on the ante-partum prolactin surge.

These results demonstrate two changes in the mechanisms controlling prolactin secretion on the last day of pregnancy compared with prolactin secretion during early pregnancy. First, feedback inhibition of prolactin secretion by PL which occurs at mid-pregnancy was not functional on the last day of pregnancy. Secondly, progesterone which promotes the nocturnal prolactin surges of early pregnancy, inhibited prolactin secretion during late pregnancy.

Journal of Endocrinology (1991) 130, 401–407

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R. L. W. AVERILL
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J. S. EVANS
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SUMMARY

Thyroidal uptake and release of 131I were used to study the response of pituitary autografts to locally infused synthetic thyrotrophin releasing factor (TRF) and porcine median eminence extract (MEE). Thyroidal release rates of 14% 131I/24h were maintained during continuous infusion of grafts with MEE (equivalent to 4 hypothalami/day) while 12·6% 131I/24 h was lost from thyroids of rats whose pituitary autografts were infused with 1000 ng synthetic TRF/day. Infusion of autografts with 5, 50 and 250 ng synthetic TRF/day resulted in lower, but dose-dependent, thyroidal responses suggesting that synthetic TRF could induce thyrotrophin (TSH) synthesis in the grafts.

At all doses of TRF, thyroidal 131I release was significantly increased by daily injection of cortisone (2 mg s.c.).

Local TRF stimulation of TSH release from pituitary grafts significantly increased the dose of thyroxine (T4) needed to decrease thyroid activity, and while 1·0 μg T4/100 g depressed activity in rats receiving saline infusions, 1·7–2·7 μg T4/100 g was needed to inhibit 131I release in rats receiving 250 ng TRF/day, and 3 μg T4/100 g was needed by rats receiving 1000 ng TRF/day.

Continuous TSH infusion (25–28 mu./day) into hypophysectomized rats induced thyroidal 131I release at rates similar to those in rats with TRF-stimulated pituitary autografts.

It is suggested that while synthetic TRF can enhance TSH synthesis in the pituitary its effects on TSH synthesis may normally be potentiated by other humoral substances.

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R. L. W. AVERILL
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H. D. PURVES
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SUMMARY

The recovery, growth, reproductive and lactational performances of rats in which thermal hypothalamic lesions had been made in one of seven different placements are described. Small medial lesions failed to alter any of the observed functions while small lateral lesions were followed by a high postoperative death rate, impaired growth, lowered mature live weight, elevated incidence of prolonged gestation and of stillbirths after normal gestations, and uniform failure of operated animals to lactate after parturition.

Two large anterior lesions are described following both of which lactation failure was again present, but other functional impairments were not always similar to those described for rats with the small lateral lesions.

These results are described in relation to earlier findings and to the possibility of differential location of mechanisms within the hypothalamus responsible for control over the endocrine factors implicated in the functional disturbances.

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J. S. EVANS
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R. L. W. AVERILL
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SUMMARY

Thyroidal uptake and release of 131I were used to study the effects of prolonged infusion of porcine hypothalamic extract on the ability of rat pituitary autografts to secrete thyrotrophin (TSH). The extract used contained insufficient TSH to induce release of thyroidal 131I in hypophysectomized rats.

After infusion for 10 days, the time of maximal uptake of 131I and onset of 131I release was significantly shortened by infusion of hypothalamic, but not cerebral cortical extract, when compared with non-infused autografted controls. The rate of release of thyroidal 131I was significantly increased by the infusion of hypothalamic extract so that by 96–120 h after the administration of 131I the rate of release was not significantly different from that in intact controls.

Accelerated thyroidal release of 131I began 42–48 h after the application of hypothalamic extracts to pituitary autografts and fell rapidly after withdrawal of the extract. At the end of 14–17 days of infusion sections of the autografts contained aldehyde-fuchsin positive staining basophils.

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R. L. W. AVERILL
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L. E. A. ROWSON
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SUMMARY

Transfers were made of 127 fertilized sheep ova to ninety-one ewes in which oestrus had been detected 1–4½ days previously. Fifty-two ewes received ova of the 6- to 16-cell stage, and forty-one of these (78·8%) gave birth to one or more lambs. Transfers were most successful where oestrus was synchronized between donor and recipient. Some sheep ova were successfully transferred after storage in vitro at between 30 and 37°C for up to 115 min. Ova at the 6-to 16-cell stage developed more frequently in ewes which had more than one corpus luteum in their ovaries at the time of transfer; of ova transferred singly 74%, and of ova transferred in pairs 75% developed into lambs.

No 2-cell ova, and only 15·8% of 4-cell ova, developed when transferred into the uterine cornua, and no 2- or 4-cell ova developed when transferred into the uterine tubes of ewes in which oestrus had commenced more than 3 days prior to transfer. The success of individual transfers was not significantly related to the breed of the recipient ewe, breed origin of the ovum, the season in which transfer was performed, or to the number and result of previous transfers made into the same recipient.

Out of thirteen ewes subjected to one or more transfers of ova, twelve subsequently conceived after matings at their first or second heat in the season of transfer.

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