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G. K. BENSON

SUMMARY

After adrenalectomy and removal of the pups from rats on the 4th day of lactation, administration of oxytocin for 9 days had little or no effect in inhibiting mammary gland involution. However, simultaneous treatment with 9α-fluorocortisol (FC) resulted in a significant maintenance of mammary gland tissue. Prolactin had an appreciable effect in retarding mammary involution, in the absence of the adrenals, but this effect was not enhanced by concomitant administration of FC, which, given alone, had only a slight effect in adrenalectomized animals. Prolactin and growth hormone (GH) together had a marked synergistic effect.

In intact rats only comparatively slight effects on maintenance of the mammary gland were observed following treatment for 9 days with either FC or adrenocorticotrophic hormone (ACTH), and ACTH failed to enhance the action of prolactin and GH.

The apparent failure of oxytocin to induce release of prolactin in adrenalectomized rats cannot be explained solely on a metabolic or nutritional basis. It is suggested that either the release of stored prolactin is inhibited in the absence of the adrenals, or that the production of prolactin is adversely affected.

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G. K. BENSON and A. T. COWIE

SUMMARY

Ablation of the posterior lobe of the pituitary in the lactating rat abolished the milk-ejection reflex so that the pups could only be reared if injections of oxytocin were given to the mothers twice daily. When, however, these posterior lobectomized rats became pregnant a second time, parturition was normal and the milk-ejection reflex was sufficiently restored for the rats to rear their litters without oxytocin being administered. The animals, however, continued to exhibit diabetes insipidus. Measurements of residual neurohypophysial tissue showed that hypertrophy of the neural stalk had occurred after posterior lobectomy.

These findings are discussed in relation to recent studies on the site of formation and the liberation of posterior-pituitary hormone(s) after hypophysectomy.

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R. C. RICHARDS and G. K. BENSON

SUMMARY

Adult female rats undergoing their first lactation were experimentally weaned by removing their pups on day 4 of lactation. The initial phase of mammary gland involution began with the removal of protein granules from the milk by digestion in large stasis vacuoles in the alveolar epithelial cells. Later stages involved a progressive necrosis of the epithelial cells by auto-phagocytosis. Removal of fat droplets and cellular debris occurred at this time and was accomplished by macrophage-like cells. Finally, epithelial cells were detached from the basement membrane and were found, in varying stages of degeneration, lying free in the lumina of the alveoli.

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G. K. BENSON and P. A. ZAGNI

SUMMARY

The administration of 1-α-methylallylthiocarbamoyl-2-methylthiocarbamoyl hydrazine (ICI 33828) to lactating rats in doses ranging from 5 to 40 mg. daily resulted in a marked inhibition of litter growth. When oxytocin (1 i.u. twice daily) was administered in addition to ICI 33828 (5 mg. or 20 mg. daily) the depression in litter growth rate was largely overcome. Histological studies indicated that the mammary glands of the treated mothers were secreting, but that the pups were unable to obtain the available milk without exogenous oxytocin. It is suggested that ICI 33828 acts on the hypothalamus by blocking the release of oxytocin and possibly enhancing the release of prolactin.

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R. M. DAS and G. K. BENSON

SUMMARY

Adult virgin, regularly cyclic female guinea-pigs were treated with different doses of luteinizing hormone (LH) and follicle-stimulating hormone during the late luteal phase of the oestrous cycle. The onset of the next oestrus was delayed and the length of the dioestrous stage was prolonged beyond the normal range in all the treated groups, but for a maximum period in the animals receiving LH alone.

The results indicate a dual role of LH on the normal cycle of the guineapig. It has been suggested that either luteotrophin release from the pituitary or an intrinsic luteotrophic action is probably a part of the function of LH in addition to its ovulation-inducing function in the guinea-pig.

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R. C. RICHARDS and G. K. BENSON

SUMMARY

Adult female rats undergoing their first lactation were experimentally weaned by removing their pups on day 4 of lactation. The macrophages of the mammary gland were labelled with trypan blue or horseradish peroxidase. Treatment with trypan blue showed the macrophages to be present in the connective tissue stroma from the 4th day of lactation to the 5th day of involution. However, on day 6 of involution they were congregated around the remaining islets of alveoli. Other cells which took up the dye were found in the epithelium of the alveoli. They were few in number on day 4 of lactation, increased numerically during the first 2 days of involution, and decreased again by day 6 of involution. Since they took up the dye in a similar manner to the lymphocytes of the regional lymph node, it is believed that they were lymphocytes. Treatment with ICI 46,474 in no way affected the course of mammary involution up to day 6. Treatment with horseradish peroxidase on day 4 of lactation or day 2 of involution resulted in labelling of the macrophages, which were found scattered in the stroma. However, by the 4th and 6th day of involution the macrophages were found to a greater extent in and around the remaining islets of alveoli.

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G. K. BENSON and S. J. FOLLEY

SUMMARY

The involution of the mammary glands of lactating rats, which normally follows the cessation of suckling, was greatly retarded over a period of 9 days by administering oxytocin to the mothers, following removal of the litters on the 4th day of lactation. This effect was obtained with a commercial extract of the natural hormone, the same extract without preservative (benzethonium chloride), and with synthetic oxytocin. Vasopressin administered under the same conditions had a less well-marked effect. No retardation of mammary involution could be obtained with oxytocin in the absence of the anterior pituitary gland.

Similar results were obtained by administering prolactin to the mothers, but growth hormone (GH) had only a slight effect in maintaining the mammary glands. When both prolactin and GH were given, the maintenance of gland structure was particularly marked.

A majority of the animals receiving synthetic oxytocin showed vaginal mucification which is taken to be indicative of the presence of a luteotrophic hormone (prolactin).

These results are discussed in relation to the possible role of oxytocin in the release of prolactin and other lactogenic and galactopoietic hormones from the anterior lobe.

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R. C. RICHARDS and G. K. BENSON

SUMMARY

Litters were removed from post-parturient rats on day 4 of lactation and the mothers were then treated with various hormones and pharmacological substances. All treatments (oxytocin, reserpine, prolactin (PR), prolactin+ growth hormone (GH), prolactin + adrenocorticotrophin (ACTH)) resulted in a significant retardation of mammary involution. Both oxytocin and reserpine treatment had little effect on the maintenance of the ultrastructure of the mammary epithelial cells, although after reserpine treatment fat droplets were more frequently observed in the epithelial cells. Treatment with PR, PR + GH and PR + ACTH resulted in a progressive maintenance of the ultrastructure of the epithelial cells, with increased fat present in these cells. However, all treatments failed to alter the distribution of the macrophage-like cells and no alteration in the lysosomes was apparent. The factors involved and the mechanisms by which these treatments might have exerted their effect are discussed.

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R. M. DAS and G. K. BENSON

SUMMARY

Pituitaries from adult or young guinea-pigs were implanted under the kidney capsule of intact adult female guinea-pigs between the 3rd and 5th days of the oestrous cycle.

The oestrous cycles in the recipients of adult pituitaries were mostly normal in length. Seven out of nine animals engrafted with pituitaries from their own litters had a prolonged dioestrus, ranging from 8 to 16 days longer than normal, at the end of which oestrus and ovulation occurred. When the grafts contained pituitaries from one male and one female pup the cycle extension was more pronounced than when they were composed of pituitaries from two or three female pups.

The occurrence of prolonged dioestrus accompanied by a delayed ovulation in the graft-bearing animals is suggested to be associated with the production of luteotrophic hormone by the graft tissue, possibly deriving from basophil cells.

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A. T. COWIE, J. S. TINDAL, and G. K. BENSON

SUMMARY

Lactating rats were implanted under the kidney capsule or in the anterior chamber of the eye with pituitary tissue obtained from their 7–8-day-old sucklings. These rats were again mated and were hypophysectomized on the 4th day of their second lactation. Injections of oxytocin were given thrice daily to induce milk ejection. In such rats the pituitary grafts under the kidney capsule gave a slight temporary maintenance of milk secretion. Substantial increases in the amount of milk and in the duration of milk secretion were obtained when the grafted animals were given daily injections of adrenocorticotrophin. The administration of antidiuretic hormone failed to increase significantly the milk yield of grafted animals. These observations are consistent with the view that such pituitary grafts secrete prolactin.